prostate cancer

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A review by Abraham et al. addressed major topics in the epidemiology of prostate cancer (114). Blacks in the USA have the highest mortality rates in the world for this cancer. They are followed by whites in Norway, Switzerland, and Sweden. The lowest mortality rates occur among Asians in Singapore, Japan, and Hong Kong. However, the incidence of prostate cancer has been rising in Japan, where major dietary changes have occurred in the last 30 y. Further, the incidence of the disease is positively correlated with that of other diet-related cancers and is much higher in Japanese immigrants to Hawaii. Studies on the relationships between prostate cancer and intake of fats and vitamin A and carotenoids are summarized in text and tables. Although evidence for an adverse effect is supported by limited animal data. For effects of β-carotene, other carotenoids, or fruits and vegetables, the data are equivocal. A protective effect of carotenoids is seen principally in the context of a low – fat diet; it is also possible the some fruits contain risk-enhancing factors. Reports of a link between cadmium and cancer risk pertain mostly to occupational exposure. In sufficient data are available on other dietary components.

Rates of prostate cancer are very low in third World countries in populations that maintain a traditional lifestyle, but they rise in urban populations where lifestyles are in transition (115). Information on risk factors for these populations is meager; neither smoking nor alcohol consumption seems to be involved. A case-control study among blacks in Soweto, South Africa, found that high consumption of fat, meat, or eggs increased risk, were as high consumption of fruits or vegetables was protective. Specific foods that afforded protection were carrots, cabbage, and spinach; dietary fiber was also protective. Employment in an occupation that permitted ready access to a Western diet increased risk. No associations were seen for anthropometry, education, social class, smoking, and drinking.

A case-control study in northern Italy identified high milk consumption as a significant risk factor for prostate cancer (116). This agrees with most previous reports. Surprisingly, however, no consistent associations were found for cheese or butter intake, other sources of animal fat, of total fat.

Ovarian cancer

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Although many “ovarian cancer families” have been indentified since epidemiologists began to look for them and by far the greatest risk is for a woman from such a family who has a first-degree relative with this disease, dietary and other factors are also involved. Piver er al. reviewed the epidemiology and etiology of ovarian cancer (123). The highest incidence is in industrialized countries, with the notable exception of Japan. Moreover, Japanese women born in the USA have rates of ovarian cancer approaching those of animal fat has been associated with ovarian cancer, whereas there is no association with use of coffee, alcohol, or tobacco. One case-control study found yogurt and cottage cheese to be the only regularly used foods associated with increased risk. At the same time, cancer patients had a lesser ability to metabolize the galactose component of lactose (milk sugar.) In general, countries with the greatest per capita milk consumption and the largest percentage of women with impaired ability to metabolize galactose have the highest incidence of ovarian cancer. Together these observations imply that exposure of ovaries to galactose increases their risk of developing malignant tumors. When whole milk and low-fat or skim milk were considered separately, however, the increased risk from high milk consumption could apparently be attributed to the milk’s fat content. Another study found no difference between cancer patients and controls infrequency of consuming dairy foods or amount of lactose consumed (124). Eating carrots reduced risk; and after adjustment for body mass, smoking, and lactose consumption, regression analysis revealed a significant protective effect of β-carotene.

Use of oral contraceptives appears to be protective against ovarian cancer but may interact with dietary factors. Harlow et al. conducted a case-control  study of the influence of diet on the association between ovarian cancer risk and use f oral contraceptives (125). The association between oral contraceptive use and ovarian cancer was modified by various nutrients; protective effects were largely confined to women with greater than median consumption of calories, carbohydrates, protein, animal fat, or lactose. Among women who ingested ≤11 g/day of lactose, use of oral contraceptives for ≥3 months was associated with a nonsignificant increase in risk; were as for those who consumed >11g/day of lactose, use of oral contraceptives for ≥3months significantly decreased risk. Within this group the association was strongest for >4 years of oral contraceptive use and >2 years of use after age 30. While this study raises more questions than it answers, it does generate several testable hypo these concerning causation of ovarian cancer. These were discussed in a commentary by Mettlin (126). In response, Cramer and Harlow elaborated on their proposed model for pathogenesis if ovarian cancer (127). They also discussed the difficulties in discriminating lactose effects from animal fat effects in most previous studies, or the failure of investigators to address this problem at all (128). They emphasized the value of measuring blood activity of galactose-1 phosphate uridyl transferase (“trans ferase”), a enzyme in galactose metabolism. Cramer and Harlow found that the ratio of dietary lactose to transferase activity was the strongest variable associated with ovarian cancer risk.

Cancer of the uterine cervix

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American Indian women in the Southwest have high rates of cervical dysplasia and cervical cancer but low rates of cancer at other sites (119). A pilot case-control study in this population evaluated the relationship between cytological abnormalities and dietary intake of various micronutrients. Forty-two women with cervical dysplasia and 58 with normal cytology provided 24-h dietary recall information. Although no differences between case-subjects and controls were statistically significant, women whose intake of vitamin C, vitamin E or folacin was low were at higher risk for cervical dysplasia. Whereas many epidemiological investigations suggest a protective role for dietary vitamin A, β-carotene, or other carotenoids, a study in the  etiology of cervical dysplasia (120). Subjects were 257 women with cervical dysplasia and 705 population controls who were thought to be free of dysplasia but were not examined cytologically when they entered the study. Information on diet and other risk factors was obtained by postal questionnaire. There was no indication that β-carotene protects against development of cervical dysplasia. In fact, there was a slightly higher risk of dysplasia in women with the highest intake of β-carotene protects against development of cervical dysplasia. In fact, there was a slightly higher intake of β-carotene. Nor could a relationship be shown with dietary retinol. Fiber and vitamin C were weakly but nonsignificantly protective.

A case- control study at major cancer treatment centers in Costa Rica, Panama, Mexico City, and Bogota, Colombia investigated dietary (121) and serological (112) indicators of risk for invasive cervical cancer. After adjustment for confounding factors, women in the highest quartiles of fruit and fruit juice consumption were at slightly lower risk. Vegetables, foods of animal origin, folacin-rich food, complex carbohydrates, and legumes were not associate with risk. Based on nutrient indices, significant trends of decreasing risk were found for vitamin C, β-carotene, and other carotenoids. However, adjustment  for vitamin C intake attenuated the effect of  β-carotene. For cancer patients, serologic investigations were restricted to those with stage I and II disease, to minimize the effects of disease on serum markers. Case-patients and controls did not differ significantly in serum levels of retinal, cryptozanthin, lycopene, α-carotene, lutein, or α-tocopherol. The mean level of β-carotene was some what lower in cancer patients; that of γ- tocopherol might represent an alteration caused by the disease process, but no evidence for a disease effect was seen for the other markers. The general concordance between dietary and serum data suggests that β-carotene has a protective role in the etiology of cervical cancer and demonstrates the discriminatory indicators.

Bladder cancer

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A case-control study of diet and bladder cancer in men was conducted in five regions of Spain (117). Each of 432 case-patients was matched with one hospital and one community control. The average dietary pattern was typical for Mediterranean populations. Subjects in the highest quartile of intake of saturated fat were at significantly increased risk of bladder cancer. Smaller risks associated with high intake of monounsaturated fats and calcium and a protective effect of iron disappeared after correcting for saturated fat. Vitamin E remained slightly protective after correction for saturated fat. No association was seen for intake of retinol, vitamin C, total vitamin A, or carotene. Tobacco smoking and occupational exposures were major risk factors but failed to explain all cases of bladder cancer in this study. Smoking and occupational exposures were also the major risk factors for bladder cancer in a German study (118). A significant twofold increase in risk was associated with heavy coffee consumption in men and women and with beer and total fluid consumption in men. Chronic urinary infection and family history of bladder cancer were also risk factors. For men, frequent consumption of high fat meals was a significant risk factor. Frequent consumption of canned foods increased risk for   both   men and women. Dietary, smoking, family history, and medical history variables did not interact with risk attributable to occupational exposure.

Prostate cancer

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A review by Abraham et al. addressed major topics in the epidemiology of prostate cancer (114). Blacks in the USA have the highest mortality rates in the world for this cancer. They are followed by whites in Norway, Switzerland, and Sweden. The lowest mortality rates occur among Asians in Singapore, Japan, and Hong Kong. However, the incidence of prostate cancer has been rising in Japan, where major dietary changes have occurred in the last 30 y. Further, the incidence of the disease is positively correlated with that of other diet-related cancers and is much higher in Japanese immigrants to Hawaii. Studies on the relationships between prostate cancer and intake of fats and vitamin A and carotenoids are summarized in text and tables. Although evidence for an adverse effect is supported by limited animal data. For effects of β-carotene, other carotenoids, or fruits and vegetables, the data are equivocal. A protective effect of carotenoids is seen principally in the context of a low – fat diet; it is also possible the some fruits contain risk-enhancing factors. Reports of a link between cadmium and cancer risk pertain mostly to occupational exposure. In sufficient data are available on other dietary components.

Rates of prostate cancer are very low in third World countries in populations that maintain a traditional lifestyle, but they rise in urban populations where lifestyles are in transition (115). Information on risk factors for these populations is meager; neither smoking nor alcohol consumption seems to be involved. A case-control study among blacks in Soweto, South Africa, found that high consumption of fat, meat, or eggs increased risk, were as high consumption of fruits or vegetables was protective. Specific foods that afforded protection were carrots, cabbage, and spinach; dietary fiber was also protective. Employment in an occupation that permitted ready access to a Western diet increased risk. No associations were seen for anthropometry, education, social class, smoking, and drinking.

A case-control study in northern Italy identified high milk consumption as a significant risk factor for prostate cancer (116). This agrees with most previous reports. Surprisingly, however, no consistent associations were found for cheese or butter intake, other sources of animal fat, of total fat.

Pancreatic cancer

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An investigation of excess pancreatic cancer mortality among workers in a chemical manufacturing plant failed to find an association with alcohol consumption or any dietary factor, other than an inconsistent association with decaffeinated coffee (108). However, other studies have identified possible diet-pancreatic cancer relationships (109-113). Case- control studies were conducted in Adelaide, Australia; Montreal and Toronto, Canada; Utrecht, The Netherland; and Opole, Poland (109). These five populations have moderate-to-high rates of pancreatic cancer and distinctive dietary practices (not specified). Comprehensive diet histories were compiled using a common protocol and questionnaire. Positive dose-related associations were consistently found for intake of carbohydrates and cholesterol, and negative associations for intake of dietary fiber and vitamin C. There was no association with weight or body mass index. In Adelaide, case-subjects consumed more boiled eggs, omelettes, and sweet and fatty food items than controls (110). They consumed less of certain vegetables, fruits, and several nutrients derived principally from plant foods. Pan creatic cancer was not associated with coffee drinking. In Opole, the association between pancreatic cancer and cholesterol intake (but not serum cholesterol) was particularly strong (111). There was a strong inverse association with vitamin C intake and weak inverse associations with retinol and fiber. The data suggested an inverse association between pancreatic cancer and intake of PUFAs and positive associations with carbohydrate and perhaps protein. In Utrecht, after controlling for confounding factors, significant inverse dose-related effects were seen for vegetables, particularly cruciferous vegetables (112). Positive dose-response gradients were found for consumption of eggs and fish. Low-fiber vegetables were more strongly protective than high-fiber vegetables in directly interviewed subjects, pointing to protective elements in addition to fiber. Vitamin C was protective in women but not in men. Consumption of beer, spirits, red wine, and fortified wine was not related to risk for pancreatic cancer in Utrecht; there was an inverse relationship for white wine consumption, but only a small number of subjects were involved (113). There was no association with lifetime consumption of tea or instant coffee, caffeinated or decaffeinated; an inverse relationship with lifetime total coffee consumption failed to reach significance (p<.06).

Lung and laryngeal cancer

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Although smoking and drinking alcohol are established risk factors for both lung and laryngeal cancer, dietary factors related to laryngeal cancer risk have been less frequently examined. Acase -control study of laryngeal cancer  in white men in western New York analyzed the interaction of diet with smoking and alcohol (95). Case – patients consumedsignificantly more fat and kilocalories than controls; their intake of carotenoids and vitamin C tended to be less. Beer, hard liquor,and total alcohol intake were strongly associated with risk; wine intake were generally low and was not associated with risk. Cigarette  smoking was also a major risk factor but use of carotenoids was most protective for light smokers, whereas risk associated with high intake of fat was greatest for heavy smokers. The relationship between carotenoid intake and risk was similar at high and low fat intakes, and conversely. High retinal intake was positively associated with risk in heavy drinkers; there was no interaction between retinal and carotenoids. When odds ratios were calculated for 129 individual foods, seven raw vegetables were significantly protective, whereas risk was positively associated with intake of mayonnaise, milk, doughnuts, veal, cooked peas, and cooked cauliflower, High total intake of raw vegetables was protective; high intake of milk and milk products increased risk. Overall, smoking was the overwhelming risk factor for laryngeal cancer. Dietary variables could modulate the effect of smoking, but their effect was much weaker.

A case – control study of laryngeal cancer in Shanghai again found cigarette smoking to be the most important risk factor (96). There was no dose-related effect of alcohol drinking on risk, but amounts of alcohol consumed were generally low. High in take of vegetables and fruits, particularly dark yellow and Allium vegetables (garlic and onions), was protective; high in take of live, salted fish, meat and eggs, and deep – fried foods increased risk. Some occupational risks were also identified , and elevated risk was linked to long-term use of kerosene stoves in cooking.

A prospective study of 4538 Finnish men evaluated the relationship between dietary  cholesterol and fatty acids and lung cancer risk (97). During 20 years of follow-up, 117 cases of lung cancer were diagnosed. In take of total and saturated fats was nonsignificantly related to risk, but no increased risk was associated with cholesterol intake. As with laryngeal cancer, the effect of fat was dwarfed by the risk associated with smoking and was mainly seen in smokers. In comparing populations whose dietary habits differ widely, however, the importance of diet is more readily seen. American men have much higher lung cancer mortality rate than Japanese (72.2 vs. 38.2 per 100,000 in 1985) (98). Nevertheless, the proportion of smokers is higher in Japan that in the USA, and although the Japanese tend to begin smoking at a later age they smoke more cigarettes per day. There  are a later age they smoke more cigarettes per day. There are no important differences inhalation patterns and type of cigarette smoked. Differences and changes in consumption of fruits and vegetables in the two countries are too small to affect lung cancer mortality, but the difference in fat consumption is striking: in 1950 and 1985 respectively, 40% and 43.5%(USA)vs. 7.9 % and 24.5% (Japan). The authors summarized mechanisms by which fat is thought to promote cancer through actions on endocrine, autocrine, and immune systems, oncogenes, gut bacteria, membrane  structure, and lipid proxides.

There were several reports that high intake of fruits and vegetable protects against lung cancer (99-101). When the relationship between dietary antioxidants and risk of lung cancer was examined in the Finnish cohort described in reference 97, nonsignificant protective effects were found for  carotenoids, vitamin E , and vitamin C in nonsmokers (99). In the total cohort, margarine and fruit were significantly protective, although again the effect was stronger in nonsmokers. The relative risk for the lowest quartile of margarine intake, compared with the highest, was 4.0 (p<.001) and for fruits was 1.8 (p=.05). The authors suggest that food sources rich in carotenoids, vitamin C, and vitamin E have other constituents with independent protective effects against lung cancer. A nested case-control study in a cohort of 41,837 women in the Iowa Women’s Health Study found that the 101 case- patients consumed significantly less tomatoes, green leafy vegetables, fruit, and all fruits and vegetables (100). The associations did not differ by smoking status, and no association was found with intake of β-carotene. Among tin miners of the Yunnan Province, China, exposure radon and arsenic increases risk of lung cancer (101). To learn whether diet affects this risk, 183 miners with newly diagnosed lung cancer and 183 age-matched occupational controls were interviewed about heir usual diet and smoking history. Miners who reported a low intake of yellow and light-green vegetables or tomatoes were at significantly greater risk for lung cancer after adjustment for radon, arsenic, and smoking. There was a monotonic relationship between quartile of intake and odds ratio for lung cancer.

Because of reports associating dietary cholesterol with lung cancer incidence, a cohort of 1878 middle-aged men who in 1958 were employed by the Western Electric Company in Chicago was followed for 24 years, to determine whether cholesterol intake was related o lung cancer in that population (102). After adjustment for smoking, age, and intake of β-carotene and fat, the relative risk of lung cancer associated with a 500 mg/day increment of dietary cholesterol was 1.9 The association persisted after adjustmen for serum cholesterol and dietary fat. Moreover, it seemed o be specific o cholesterol from eggs.  Mean values for dietary cholesterol from eggs and other sources were 238 and 491 mg/day, respectively, but 11 other foods or food groups that could provide appreciable amounts of cholesterol were not significantly associated with lung cancer risk. One interpretation of these results is that something associated with eggs besides cholesterol is a risk factor for lung cancer. However, reanalysis of data from a case-control sudy in Hawaii to look for an “egg effect” failed to corroborate the findings of the Western Electric study (103). There was a significant positive trend of the odd ratio with increasing consumption of total cholesterol and cholesterol from sources other than eggs for men but not women.

The mortality rates of lung cancer were greater in the north of Italy than in the south in 1980 and 1982, although the proportions of smokers, surveyed in 1977, were similar (104). Information on dietary habits derived from annual surveys conducted form 1960 through 1965 showed hat the diet in southern Italy contained less saturated and polyunsaturated fat and more foods of plant origin than the diet in northern Italy.

The lung cancer rate among men in Gejiu City, Yunnan Province, China, is one of the highest in the world (105). In this in-mining community, rice is the dietary staple and bean curd is the primary source of additional protein. A case-control study of diet and lung cancer risk was conducted because it was thought that in this situation the simplicity and relative homogeneity of the diet serve to highlight links between die and lung cancer. Where possible, each case-subject was matched with a miner control and a Gejiu City control and was queried about usual frequency of intake of 31 food items and food groups. Case-subjects ate rice and noodles some what more often than controls, but ate most other items less often. The difference were significant for bean curd, meat (pork), eggs, fresh greens, tomatoes, dark-green leafy vegetables, light-green vegetables, bananas, oranges, and apples. In take of pork, eggs, and the three fruits was directly related to income and education, which were inversely related to lung cancer risk. Case-control differences nevertheless persisted across income and education strata. By regression analysis, results were similar across duration categories of underground mining exposure. Nonsmokers were too few to permit evaluation of dietary associations in this group. The results provide further evidence that fruits and vegetables are protective against lung cancer but do not support the theory that β-carotene is specifically responsible for the effect.

In addition to protecting against lung cancer, fruits and vegetables may lengthen survival of lung cancer patients. (106). Analysis of records from the Hawaii Tumor Registry showed covariate- adjusted median survival times for women of 33,21,15 , and 18 month from the highest to the lowest quartiles of vegetable intake. There was also a significant trend for fruit intake and survival in women. High consumption of tomatoes or oranges signifcanly improved survival in men; broccoli and perhaps tomatoes were beneficial in women. No associations were beneficial in women. No associations ere found for consumption of specific micronutrients or of other carotene-rich foods.

To confirm findings of a cohort study in which an excess of lung cancer occurred among certain groups of meat industry workers, a nested case- control study of lung cancer in the meat industry was undertaken (107). It confirmed the existence of excess risk of lung cancer throughout the meat industry. Risk increased with duration of employment in the meat industry. The major risk factors for meat handlers compared to workers in non-meat industries were contact with raw meat for ≥5y, contact with raw meat in abattoirs, and contact with raw meat in supermarkets. However, workers having contact with raw meat in meat-packing plants and supermarkets in these departments who did not have direct contact with meat, suggesting that other occupational risk factors may be involved, such as exposure to fumes from heat-sealing plastic during wrapping.

EPIDEMIOLGY

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Cancer epidemiologists are eager to exploit Europe’s opportunities to understand the causes of cancer (20). Each of some two dozen nations has its own distinctive cuisine, customs, climate, genetic makeup, and cancer rates; these factors frequently very  regionally within a country, as well, Europe’s largest epidemiological database is being established at the International Agency for Research on Cancer in Lyons, France. A wide range of prospective studies are in the planning stage. Some patterns have already been identified: for example, south-to-north gradients in death rates for all cancers, and malignant melanoma. The rarer cancers of the liver, esophagus, larynx, and buccal cavity are more frequent in the south.

In epidemiology, case- control and cohort studies can be viewed as alternative conceptualizations of the same problem (21). Although two major types of bias, selection and recall, occur more frequently in the former, case – control studies are generally more manageable in terms of size and cost. The authors weighed the advantages and disadvantages of case – control studies on the role of nutrition in cancer etiology and discussed several studies done in Athens. For colorectal, stomach, breast, and lung cancer, diverticulosis, and cholelithiasis, high vegetable intake was generally protective, where as evidence for other food groups and constituents was variable and less convincing.

Difficulties in interpreting cancer incidence and mortality data were discussed by Doll (22). Mortality data have historically been more complete and reliable than incidence data, but the correlation between incidence and mortality has become progressively weaker since about 1960, when rapid progress in cancer treatment began. Whith the establishment of comprehensive tumor registries and screening programs, incidence may be more apparent than real. Although  this paper was a general epidemiologic assessment of progress against cancer, Doll’s points apply to studies of nutrition and cancer and he specifically considered changes possibly related to fat consumption. Nothing that fat disappearance statistics in several countries parallel decreases in incidence of colon cancer, he proposed other factors that could account for at least part of the change. These include a trend to classify cancers of the colorectal junction as rectal rather than colonic, increased consumption of non digestible carbohydrates and perhaps cruciferous vegetables, and  widespread use of prophylactic colectomy for familial adenomatous  polyposis. Reduced incidence of ovarian and endometrial cancer could be due at least in part to use of newer combined steroid contraceptives. If reduced intake of saturated fat has had a beneficial influence on incidence of breast and prostate cancers, this has been masked by other factors (such as widespread screening programs) causing thee cancers to be recorded more often.

Cross-cultural epidemiologic cancer research in Hawaii has been facilitated by the Hawaii Tumor Registry (23). Descriptive studies reveal wide ethnicdiversity in cancer incidence and survival, which correlates with culture and lifestyle, particularly dietary practices. Incidence rates are presented for men and women by sit and ethnicity. These data are discussed in terms of diet and compared with populations in the respective homelands. Similar studies in Argentina found that mortality rates from gastric cancer were higher in most countries of origin than in the respective Argentinean immigrants and were lowest of all in native-born Argentineans (24). In contrast, mortality from esophageal cancer was higher in Argentina than in Europe. Only Uruguay and Germany had higher mortality rates than Argentina for breast and colon cancer, and migrants’ risk for these cancers converged toward that of Argentinean. Risk for liver cancer was somewhat lower in South American migrants to Argentina.  Differences existed for cancers of other sites as well. When variation in the reliability of death certification and other confounding  factors and bases were considered, dietary variable –most notably meat, fat, and beer consumption –remained an important probable influence.

The lifestyle of Seventh-Day Adventists (particularly in its emphasis on vegetarianism and abstinence from biblical “unclean” foods, drugs, alcohol, tobacco, and caffeine-containing beverages) is regarded as protective against cancer. In Norway, where the incidence of cancer is generally low, the standardized incidence of cancer is generally low, the standardized incidence ration (SIR) for Seventh –Day Adventists (Compared with the general population) did not differ significantly from unity (25). For lung and other respiratory cancer and “other unspecified diagnoses” the SIR was somewhat lower for Seventh-Day Adventists; for cancer of the uterine corpus and “other female genital” cancers it was higher. Incidence rates in relatively new members tended to exceed rates for long-time members, but the study did not distinguish between religiously active and inactive and inactive Adventists. A possible conclusion from this study is that the main factors in cancer etiology in Norway are different from the factors in which Seventh-Day Adventists. A possible conclusion from this study is that the main factors in cancer etiology in Norway are different from the factors in which Seventh-Day Adventists differ from the general population.

A study in western New York state looked at the role of putative cancer risk factors embedded in dietary patterns (26). Seven dietary patterns were identified in men and seven in women. Associations were examined between them and intakes of alcohol, energy, total fat, and dietary fiber, type of fat, and smoking and high-fat dietary patterns incorporating numerous sources of saturated fat. Alcohol use in women was unrelated to smoking or to intake of fat or total energy. Thus men and women showed distinctive eating styles that exposed them differentially to putative cancer risks. Additive effects were clearer for men than for women.

A prospective study of women in Sweden suggested that nonprotein energy intake was a positive risk factor for cancer (27). Dietary fat did not fully explain the increased risk associated with energy intake. While there was a possible negative association between relative protein intake and all-site cancer, the conclusion that energy intake from nonprotein sources is a determinant of cancer was better supported by the data.

In a series of hospital- based case- control studies in northern Italy, relative cancer risks were determined by tertile of vegetable and fruit consumption, based on a food-frequency questionnaire (28). More than 8000 cancer patients and 6000 controls participated in these studies. Corrections were made for age, sex, area of residence, education, and smoking. Vegetables consistently protected against epithelial cancers, relative risk in the upper  tertile ranging from 0.2 for esophagus, liver, and larynx to 0.7 for breast. Begetables afforded no protection against nonepithelial lymphoid neoplasms. High fruit consumption protected strongly against cancers of the upper digestive and respiratory tract; with sites lower in the digestive tract the protection became progressively weaker. Protection was significant for liver, pancreas, prostate, and urinary sites but not for rectum, breast, thyroid, or female genital cancers. There was no protective effect of fruit against lymphomas or myelomas.

Because xanthophylls, as well as β – carotene, may protect against smoking – related cancers, Japanese investigators determined the relationship between serum xanthophyll levels and consumption of cigarettes, alcohol, and certain foods in healthy inhabitants of Japan (29). Women had significantly higher intake than men of milk, pulses, gree and other vegetables, and fruit. Serum zeaxanthin and β – carotene concentrations were positively correlated with intake of green vegetables, eggs, and milk for both sexes; serum levels of β-cryptoxanthin were correlated with intake of fruit, milk, pulses, and green vegetables for men and fruit for women. By stepwise multiple refression analysis, β – cryptoxanthin and β – carotene concentrations were inversely associated with cigarette and alcohol consumption.

Although the Italian studies (described in 28) showed no overall relationship between tea drinking and cancer risk (30),Chinese green tea may afford protection against smoking – related cancers (31). The micronucleus test is a standard genotoxicological assay. Analysis of matched – pair data for healthy smokers and nonsmokers showed that smoking significantly increases micronucleus formation I peripheral- blood lymphocytes. Alcohol increases micronucleus formation in smokers still further, whereas tea decreases the micronucleus formation induced by smoking

The frequent finding of an association between low blood cholesterol levels and increased cancer risk is of considerable concern in light of effort to reduce cholesterol to prevent heart disease. Kritchevsky evaluated results of the strongest relationships between low cholesterol and increaxed cancer risk (32). He compared diets of participants who developed cancer and those who did not. His theory was that if diet could account for the lower cholesterol levels of the cancer patients then dietary manipulations to reduce cholesterol must be reconsidered-whereas if diet did not explain the difference, other hypotheses for the association would have to be sought. Besides a 24-hour dietary recall measure taken at baseline, information on participants’ smoking habits, alcohol consumption, education, family income, height, weight, and body fat distribution was also available. Dietary fat and cholesterol consumption were directly associated with cancer occurrence in men but inversely associated in women. However, in men, diet could not explain the blood cholesterol- cancer relation. Whatever mechanism linked low blood cholesterol and high dietary cholesterol to cancer, it appeared to be related to the body’ hormonal or metabolic milieu, and the distribution of body fat was involved. Men with peripheral adiposity who developed cancer tended to consume less cholesterol than those who did not, whereas the opposite was true for men with central adiposity. Among women who had peripheral adiposity, cancer was directly serum cholesterol; for central adiposity the some inconsistencies in the literature may be explained by differing proportions of central adiposity in study populations.

In Finland, investigators looked for associations between serum concentrations of α- tocopherol , β –carotene, retinol, retinol – binding protein, and selenium and the subsequent occurrence of cancers of low incidence (lip, oral cavity, pharynx, larynx, esophagus, liver kidney, gallbladder, urinary bladder , brain, and skin) (33). Nearly 40,000 adults participated in the nested case – control study. Although several sites showed a trend toward elevated cancer risk and low levels of the serum variables, the association reached statistical significance only for bladder cancer and retinol- binding protein (p=.05) and for melanoma and α –tocopherol  andβ – carotene (p’s<.01) Because the total number of these cancers was small (115), no firm conclusions could be drawn from the results. A similar study compared case- control differences in prediagnostic serum levels of retinol, β –carotene, vitamin  E, and selenium  for 10 cancer sites in 10 study populations (34). Low levels of β – carotene were most likely to be associated with subsequent cancer, but there were marked differences in the strength of the association according to site. A low level of retinol did not appear to be an important risk factor for cancer at any site. Prediagnostic levels of vitamin E and selenium were generally lower in case- patients than in controls, but the differences were seldom greater than 10% The relative specificity of particular antioxidants for protection at particular sites, the advantages of dose-response studies over case- control studies, and the problem of amassing sufficient data for the rarer sites were discussed. The authors suggest that a measure of total serum antioxidant activity be developed to supplement data on individual substances. For squamous cell skin cancer, these authors found that case- patients had higher median micronutrient levels than controls for all micronutrients but selenium (35). If levels above the median are considered high, case-patients were more likely than their matched controls to have high levels of retinol- binding protein. Selenium was inversely associated with risk of squamous cell skin cancer; no association was seen for β – carotene. Although these results provide some evidence for a protective role for selenium, they do not support an anticancer role for the other micronutrients.

High intake of fruits, vegetables, and carotenoids and high levels of β-carotene in the blood are consisitently associated with reduced risk of  lung cancer frequently with reduced risk of certain other cancers, as well. The simplest explanation, but not the only one, is that β – carotene is protective. Other carotenoids, other constituents of the fruits and vegetables, or dietary patterns tightly linked with frequent vegetable and fruit consumption could also be invoked to explain  the results. A group of investigators from the National Cancer Institute and elsewhere are conductiong a comprehensive study to identify dietary patterns that are highly correlated with fruit and vegetable intake and to develop and test a liquid chromatographic method for recovery and resolution of the common carotenoids in blood (36). They are also considering the individual carotenoid composition of foods when analyzing relationships between diet and cancer prospectively and retrospectively. Repeatedly, they find stronger associations with intake of foods (total vegetables, dark green vegetables, yellow-orange vegetables, Two possibilities, which the authors plan to investigate further, are that intake of food groups rich in β – carotene intake than is an approximate index of the hydrocarbon carotenoids, or that the protective agent is one or more other constituents of these foods.

Block reviewed the epidemiologic evidence for a protective effect of vitamin C against cancer (37).She found it to be very strong for 11 cancers of epithelial origin, but not for 11 cancers of epithelial origin, but not for 4 hormone- dependent cancers. All 8 studies that reported a vitamin C index in cancer of the oral cavity, larynx, or esophagus found a significantly higher risk associated with low intake. Of 11 lung cancer studies that specifically mentioned vitamin C, 5 found a significant protective effect, 4 found a nosignificant protective effect, and 2 found no effect. Five of 6 studies that examined the risk of pancreatic cancer in relation to either vitamin C intake and risk of stomach cancer found a significant protective effect. Vitamin C or fruit intake found significant protection. All 7 studies on vitamin C intake and risk of stomach cancer found a significant protective effect. Vitamin C appears more strongly and consistently protective against rectal cancer than against colon cancer, but some protection against colon cancer is observed. When the diets of  pregnant women were investigated I a study of child hood brain tumors, low intake of vitamin C was significantly associated with a threefold increase in risk of brain tumors in the offspring.

Although vitamin C does not afford significant protection against hormone- dependent cancers, a study in Japan suggested that dietary phytoestrogens may (38). Certain lignans and isoflavonoids in the traditional Japanese diet are converted by the intestinal micrflora to weakly estrogenic substances exhibiting a variety of antiestrogenic, antiproliferative, antiviral, cytotoxic, and growth-inhibiting effects. By stimulating the production of sex hormone-binding globulin in the liver they may influence the biological activity of sex hormones. Urinary excretion of these substances was studied in 10 women and 9 men living in a rural Japanese village, who ate the typical low-fat Japanese diet based on rice, soy products, fish, and vegetables. Urinary excretion of lignans was low, but excretion of isoflavonoids was very high and correlated with consumption of soybean products. It has been suggested that the low mortality rates from breast and prostate cancer in Japan are related to the high intake of soybean products.

Gastric and esophageal cancer

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A hospital-based case-control study of stomach cancer in high – and low risk areas of the Federal Republic of Germany identified several possible diet- related risk factors (72). In addition to material collected from the case-control study, data on traditional habits going as far back as 1910 were analyzed. From the historical data, use of vegetables and legumes was associated with the low-risk area, whereas mashed potato, cabbage, and farinaceous dishes were dominant in the high-risk area. Cultivation and use of tomatoes began relatively late in the high-risk area. The traditional wood used for smoking in the low-risk area was beech; various woods, including spruce, were used in the high-risk area. From the case- control study, low intake of vitamin C, noncentralize water supply, refrigerator use for <25 y , and use of spruce wood for smoking meat at home were associated with increased risk of gastric cancer. These associations applied to both individuals and regions. A similar study in two Belgian provinces with contrasting gastric-cancer mortality retes indentified other dietary risk factors(73). Consumption of most raw or cooked vegetables and fresh fruit (especially apples) was protective, as was consumption of lean meat. Increased risk was associated with meal and flour products, including white bread, and sugar. In contrast to other vegetables, beans increased risk for gastric cancer; this, however, may support the findings for carbohydrate rich foods. Most sources of fat did not show a clear effect, but oils with a high ratio of polyunsaturated to saturated fatty acids were associated with decreased risk.

Another case-control study was conducted in four provinces of Spain (74). One was a low-risk area; the others had relatively high rates of gastric cancer. From 15 hospitals,354  cases of confirmed gastric adenocarcinoma were selected, along with a control for each from the same hospital matched by age, sex, and area of residence. Information on diet was  btained from dietary histories and frequency questionnaires. Increased risk was associated with habitual consumption of preserved fish, cold cuts, and oily fruits. Cooked green vegetables, fresh noncitrus fruit, and dried fruit were protective. Effects were additive: high intakes of a protective food groups enhanced protection, and conversely. This observation may have practical implications for public health campaigns, because efforts to get people to eat more of some thing are generally more successful than exhortations to eat less of something. Preference for salty foods and addition of salt at the table were not associated with risk.

In Italy, gastric cancers I high- and low-risk areas may differ by histologic type (75). When 923 tumors were categorized according to the Lauren classification, intestinal types outnumbered diffuse by 3:1 in the high-risk north-central region, whereas the two types were equally abundant in low-risk areas. Intestinal types were also more common at older ages and in men. However, diet-related risks for the two types were similar: increased risk was associated with high intake of meat, dried or salted fish, seasoned cheeses, and traditional soups, whereas heavy consumption of fresh fruits and vegetables was protective. Indices for specific nutrients associated with the food groups showed the same risk patterns as the foods. Occurrence of both histologic types was inversely associated with socioeconomic status but urelated to cigarette smoking. Thus, despite other differences, the intestinal and diffuse types f gastric carcinoma appear to share common etiologic factors. Sixty-eight of the 923 tumors occurred in the gastric cardia (76). Compared with other gastric cancers, these were more common in men than in women and had a reater tendency to be associated with a family history of this cancer. Dietary risk factors were the same as for gastric cancer ingencral, considering the limited data for the cardia site. However, the proportion of cardia tumors in this study is much smaller than that reported by countries where sharp increases in the incidence of cancers of the cardia and lower esophagus have recently been noted, suggesting a need for research on environmental and host determinants of this emergent tumor.

Fresh fruits were significantly protective against gastric cancer in a smaller case-control study in rural Leon, Spain (77). Consumption of home-made sausages or home-cured meats conferred some risk, which reached statistical significance f the meat were smoked. There was a nonsignificant protective effect from consumption of fresh vegetables.

A prospective study of gastric cancer mortality in a cohort of initially healthy high-risk men suggested that excess gastric cancer risk in the North Central USA is partly due to foreign birth or having an immigrant parent from Scandinavia or Germany, where risk is also high (78). An association between low educational attainment  and laboring or semiskilled occupations was found only for foreign-born and first- generation Americans. The strongest risk factor in this study was cigarette smoking, and it was dose-related; risk was also increased among pipe smokers and men who used smokeless tobacco. No excess risk was associated with drinking alcohol. When dietary factors were examined, none of the 7 food groups (meats, fish, dairy, breads, fruits, vegetables, cruciferous vegetables) was significantly associated with risk, but several of the 35 individual food items were risk factors: salted fish, bacon, milk, cooked cereal, and apples. One explanation offered for the surprising association between apple consumption and increased risk was that quantities of apples were customarily stored in conditions under which they could become moldy. Patulin, a mycotoxin contaminant found in apple products, induces sarcomas in rats at the injection site.

Kashmir has nonmigrant population of Muslims, Hindus, and Sikhs with distinctive personal and dietary habits (79). Overall its rate of esophagogastric cancer is very high, but the rate among Hindus is relatively low. Muslims and most Hindus do not drink alcohol, whereas alcohol consumption is common among Sikh men. Smoking is common among Hindu and Muslim men, and Nuslims frequently use snuff; Sikhs do not smoke. Up to 10 cups per day of salted tea, boiling hot, is drunk by Muslims; Hindus drink 2-4 cups per day of green tea boiled with spices. Most Kashmiries have an adequate intake of locally grown fruit. Their staple diet is boiled rice and a boiled leafy cruciferous vegetable. Most of them eat lamb. Other special food items are dried and pickled vegetables, sundried and smoked fish, red chilies, lotus stem, other local cegetables, mixed spice cake, saffron, and mawal (Celosia argentea, a vegetable food colorant). Because of the large number of gastric (996) and esophageal (1515) cancer diagnosed during the three-year study in a valley whose population is ~2.9 million, a study of dietary risk factors seems important.

Rapid social changes in Hong Kong during the past 20 years have produced considerable heterogeneity in exposure to possible etiologic factors for esophageal cancer, enhancing the likelihood of detecting both risk factors and protective factors for this tumor in a population whose risk is high by international standards (80). In a study of 400 patents hospitalized for esophageal cancer and 1598 hospital and clinic controls, interviewers questioned subjects about sociodemographic  characteristics, smoking, drinking, tea and coffee consumption, and personal and family medical history. A food-frequency questionnaire inquired about past and recent consumption of 22 food items. The foolowing significant risk factors were identified by multivariate analysis: tobacco smoking, alcohol drinking, preference for high-temperature drinks and soups, infrequent consumption of green vegetables or citrus fruits, and consumption of pickled vegetables. Assuming that risk is multiplicative, the combined attributable risk is multiplicative, the combined attributable risk due to these exposure was 89% In preliminary analyses, protective trends were seen for carrots, tomatoes, and noncitrus fruits; low educational attainment and eating salted fish increased risk. Support was given to the assumption of multiplicative risk by a modeling study in Italy (81). In this study of 211 men with esophageal cancer and 712 controls, an additive model was inadequate for describing relative risk, but the data fitted a multiplicative model. Major risk factors were alcohol and tobacco consumption and a low β- carotene index. Retinol index had no association with risk. Case-patients were less educated and of lower social class than controls. The use of statistical modeling in studies such as this is discussed. In Transkei, extensive inquiries were made into the diet and social habits of 100 esophageal cancer patients and 100 controls (82). Regression analysis identified smoking, use of traditional medicines, and consumption of black nightshade (Solanum nigrum) as significant risk factors. Drinking traditional beer was not a risk factor. The findings are discussed in terms of the rapid increase in incidence of esophageal cancer in Transkei since 1950, which has accompanied population expansion, reduced availability of milk, meat, sorghum, and millet, and greater dependence on corn and perhaps wild vegetables.

Adams briefly reviewed the literature on relation-ships between hormones, fat, and breast cancer (83). He made the following points: (i) Japanese women have a much lower incidence of breast cancer than Americans, but the difference disappears within two generations when they migrate to the USA; (ii) positive association between breast cancer risk and intake of saturated fats is repeatedly seen in postmenopausal women; a similar association exists between breast cancer risk and body mass index, again only for postmenopausal women; and (iii) hormones, particularly estrogens, are thought to act as promoters of breast carcinogenesis. Experiments with rodents support observations in humans. When hormone profiles of American and Japanese women were compared, dehydroepiandrsterone sulfate (DHEAS) concentrations were significantly higher in the blood of Americans. An estrogen, 5 – androstene- 3β,17β-diol, is formed peripherally from this and in Western women peripherally from this and in Western women it reaches biologically active levels. Urinary metabolites of DHEAS, 11-deoxy-17 keto-steroids, were also higher in American women DHEAS, its metabolites, and incidence of breast cancer and leads Adams to hypothesize a direct link between diet, secretion of hormones (especially DHEAS), and development of breast cancer. He suggests that diet and body fat provide fatty acids that act directly or indirectly on the mammary gland and augment prolactin and DHEAS secretion, girls produced the opposite results and conclusions (84). When hormone levels of vegetarian (Seventh-DayAdventist) and nonvegetarian girls in the Chicago area were compared, vegetarians had somewhat higher DHEAS luteal and follicular levels than novegetarians, with a significant difference in the luteal phase of the menstrual cycle. The authors cited other evidence for an inverse relationship between DHEAS levels and breast cancer risk. Vegetarians in this study ingested significantly less total fat, saturated fat, sucrose, cholesterol, protein and caffeine and significantly more unsaturated fat and fiber than nonvegetarians, but none of these nutrients was associated with DHEAS. Nevertheless, the link be tween a vegetarian diet and DHEAS suggests how low-fat diets during adolescence may reduce subsequent breast cancer risk.

A review by Rose uses evidence from epidemiologic and animal studies to suggest how dietary fiber may modify the putative adverse influence of fat (85). The mechanisms by which fiber protects against breast cancer probably involve estrogen metabolism and bioactivity through effects of fiber on the enterophepatic circulation of estrogens, enhanced fecal excretion of estrogens, and actions of fiber-associated phytoestrogens. Phytoestrogens have weak estrogenic activity, but by competing with more potent estrogens for receptor binding sites they may exert a net antiestrogenic effect. Thus a diet rich in phytoestrogens might downregulate estrogen bioactivity and protect against breast cancer.

A case-control study in Moscow found that dietary factors are more important for postmen- pausal than premenopausal breat cancer (86). A decreased risk for postmenopausal breast cancer was associated with high intakes of cellulose, monosaccharides and disaccharides, vitamin C, β-caro-tene, and polyunsaturated fatty acids (PUFAs).High protein intake was a risk factor with a very high odds ratio but also very wide confidence limits. Alcohol was a risk factor for both premenopausal and postmenopausal women, but it reached significance only in the postmenopausal and postmenopausal case-patients and controls were discussed.

The role of diet in breast cancer development was evaluated in an Australian case-control study (87). Groups of 100 patients with breast cancer, benign epithelial hyperplasia, or fibrocystic disease and roughly 200 control subjects participated. Cancer patients and controls were matched by age and electoral district. Patients with fibrocystic disease were matched to those with benign epithelial hyperplasia, and these groups shared the same control. The authors hypothesized that dietary patterns of the group with fibrocystic disease (notconsidered a risk factor for cancer) would resemble dietary patterns of controls, whereas patients with benign epithelial hyperplasia (a probable precursor of malignancy) were expected to resemble cancer patients in their dietary patterns. The results supported this hypothesis. Consumption of red meat, “savory meals,” or starches increased risk of hyperplasia and neoplasia, whereas consumption of chicken and fish or fruit was protective.

A prospective case-cohort study conducted  on the island of Guernsey found plasma selenium concentration to be at most a weak indicator of breast cancer risk (88). However, only a limited and moderate range of  selenium exposures and a relatively short time span (10 years) were considered.

An epidemiological study of postmenopausal breast cancer in western New York confirmed that risk increases with a family history of breast cancer, a history of benign breast disease, high body mass (Quetelet) index, and age at first pregnancy and decreases with number of children and pregnancies (89). After adjustment for confounding factors, risk was highest among women with the lowest consumption of carotene or substances correlated with consumption of carotene. Risk was not associated with retinol ingestion or with fat intake, whether in terms of quantity or proportion of total energy intake.

In extending to 8 years the follow-up of nearly 90,000 women enrolled in a health study, Willett et al. Found no evidence to suggest a major adverse influence of total or saturated fat intake by middle-aged women on breast cancer risk (90). However, in this same study population, consumption of vitamin A (including supplements) and vitamin E showed inverse relationships with breast cancer risk(91). The association was significant for vitamin A but nonsignificant for vitamin E; both associations were slightly stronger for premenopausal than for postmenopausal women. No association was seen for vitamin C.

Death rates from breast cancer in southern Italy are low, but in northern Italy they have recently approached rates in the USA (92). Distinctive dietary patterns are found in these three areas. Southern Italy has the lowest consumption of meat, milk, and cheese and the highest consumption of fish, bread and baked goods, pastas, and vegetables. Notthern Italy has the highest consumption of cheese and fruits and the lowest consumption of  cheese and fruits and the lowest  consumption of fish. The USA has the highest consumption of meat, milk, and eggs and the lowest consumption of bread and baked goods and pastas. High consumption of olive oil characterizes southern Italy, whereas butter intake in northern Italy is three times higher than in the south and is similar to that in the USA. Vegetable oils other than olive oil were little used in Italy before 1970; since then they have come to represent more than one-third of the fats in both north and south.

In a case-control study of breast cancer in Argetina, where the mortality rate for this disease is high, information was obtained on demographic, socioeconomic, and reproductive variables, frequency of consumption of 40 food items, and methods of cooking (93). After nondietary risk factors were controlled for, weak positive associations were found between breast caner risk and intake of beef, fried foods, and > 3 eggs per week. The most likely reason for failure to find strong associations with dietary factors was lack of sufficient heterogeneity in nutritional exposures within the study population. The authors had expected to find a stronger relationship between breast cancer risk and beef consumption. Failure to find one may mean that non exists; however, beef consumption was high (generally>4 times per week) in both case and control groups.

Evidence is accumulating diet can influence survival of cancer patients as well as the initial development of their disease. However, a study of breas concer patients in Denmark found no prognostic significance for reproductive or hormonal risk factors, dietary variables, alcohol consumption, or smoking

colorectal cancer symptoms

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Colorectal cancer

The expression “colorectal cancer” refers nonspecifically to three cancers with distinctive epidemiologic and etiologic features. Failure to distinguish among these is the source of much confusion in the literature. Weisburger reviewed the epidemiology, causes, mechanisms, and prevention of cancers of the proximal and distal colon and rectum (38). He cited findings from animal studies, geographical epidemiology, studies of migrants and subpopulations that adhere to distinctive traditions, and time trend. The roles f activity, iatrogenic factors, associated diseases, sex, and genetic elements were considered. Genotoxic and nongenotoxic mechanisms of carcinogenesis were explained and protective factors were discussed.

The evolution of colorectal cancer from normal mucosa is driven multifactorially (40). In heritance and diet are critical; physical activity, alcohol consumption, and body composition are also involved. Dietary influences come into play at each stage of the multistage carcinogenic process, but their effect may depend on genetic factors. Definitive understanding of the relationships between diet, inheritance, and colorectal cancer await  the results of large prospective, randomized intervention studies such as have recently been initiated in Europe and the USA’ Giovannucci et at.Reported one of the few studies of the relationship of diet to risk of colorectal adenomas, which are early precursors of cancer (41). Using data from food-frequency questionnaires completed by 7284 male health professionals who had had a colonoscopy or sigmoidoscopy, they determined relative risk of adenoma by quintile if nutrient intake. After adjustment for total energy, risk of colorectal adenoma was positively associated with intake of saturated fat and with the ratio of red meat to fish and chicken intakes, and inversely associated with intake of all sources of dietary fiber. Because adenomatous polyps frequently appear 10 years or more before the clinical diagnosis of cancer, this study links dietary factors with events very early in the transition from normal mucosa to malignancy.

Disagreements over the relative roles of different dietary factors in development of colon cancer frequently originate in the high correlations between nutrients and the ways in which researchers try to compensate for these correlations. (42). This paper described and applied as set of diagnostic tools for assessing the magnitude of collinearity in epidemiologic data, reviewed four methods for addressingcollinearity problems in multivariate egression models, and evaluated the results from application of each method data from a case control study of diet and colon cancer. Although the study addressed only the potential collinearity problems between total fat and total caloric intake, similar difficulties would arise for total protein and total caloric intake. The fundamental problem with multicollinear nutrient data is that they contain insufficient information to discriminate the in fluence of highly correlated nutrients. Therefore the epidemiologist must impose constraints on the data to address analytical problems associated with collineariy; how to do this is a critical element of the procedures described in this paper.

Another problem in comparing case-control studies of colorectal cancer relates to the type of dietary information used-retrospective versus original (43). To evaluate the seriousness of this, participants in a cohort study who had dilled out a dietary questionnaire in 1967 (original information) were asked to fill out a similar questionnaire in 1987, with reference to their dietary habits in 1967 (retrospective information). All 50 surviving subjects who had had a diagnosis of colorectal cancer completed the questionnaire in 1987, as did 150 controls selected at random from original participants who did not have colorectal cancer. Case- subjects and controls had a similar tendency to misestimate their previous food intake, and this tendency was closely related to changes in consumption during the intervening years. Subjects whose dietary habits had not changed appreciably provided retrospective information that agreed  well with the original. However, compared with controls, case-subjects tended to underestimate their previous consumption of coffee and sweets and overestimate their consumption of eggs, fruits, and vegetables when their original estimate had been “high” When the original estimate was “low,” case-subjects more frequently overestimated previous consumption of fruits and vegetables, whereas controls overestimated previous consumption of potatoes and milk. When changes in dietary habits were analyzed, case-subjects and controls sowed similar changes.

A case-control study of the relationship of diet to occurrence of colorectal cancer in Athens, Greece, characterized a high-risk diet as high in protein, saturated fat, and cholesterol, and low in vegetables- the opposite of a low-risk diet (44). However, case-subjects had substantially and highly significantly lower serum levels of total cholesterol and high-density lipoprotein (HDL) cholesterol than controls. Thus, again, diet could not explain serum cholesterol values (see 32). Alternative explanations for this well known paradox are discussed in terms of the data from this study.

A case- control study in Sweden found a positive association between colorectal cancer and usual meat consumption during the previous five years (45). High total meat intake, frequent consumption of brown gravy, and preference for a heavily browned meat surface each independently increased the risk; and the risk was greater for rectal than for colon cancer. Surprisingly, consumption of boiled meat was associated with greater risk than consumption of meat fried lightly. Although it has been known for some time that carcinogens are formed when meat I cooked at high temperatures, this is one of the few epidemiologic studies to consider the method of cooking.

In a prospective study of nearly 90,000 women, Willett et al. found an association between intake of red meat and colon cancer (see Chapter 2, Food Safety 1991, reference 27). Numerous readers have commented on this study (46-53). It was noted that the authors failed to distinguish between cancers of the proximal and distal colon, which are thought to have different pathogenetic mechanisms and whose relative incidence in women varies with age (46). Nor was the possibility of hereditary nonpolyposis colorectal cancer considered in the data analysis. In lumping beef, pork, lamb, and processed meat products such as bacon and sausage into the category “red meat” the authors failed to account for the huge range of fat content and possible role of other constituents, especially in processed meats (47). They also did not discuss other aspects of “healthy” and “unhealthy” lifestyles that tend to be associated with healthy and unhealthy diets (48). A practitioner of family and sports medicine was concerned that active women and girls already at risk for iron deficiency might turn away from the best source of iron available to them, when the only significant risk was associated with consumption of more than a quarter of a pound of red meat daily (49). Estimates of dietary fiber used in this study may have been less than ideal and could have had a major effect on conclusions from the study (50). The possibility of a detection bias was suggested (51). High meat consumption would cause more positive tests for occult blood in the stool, and investigation of these could yield some incidental diagnoses of colon cancer. Willett et al. explained why this was unlikely in their study (54). In response to another comment (52), they explained why they did not analyze total mortality in their relatively young population. Finally, a reader looked at the 2:1 risk ration for colon cancer in meat eaters compared with fish eaters from a different perspective (53). Meat eaters had an incidence of colon cancer of 0.113 %, whereas the incidence in fish eaters was 0.059% difference in these rates is seriously worth worrying about. Willett et al. argued that it is (54), considering the young age of the study population and the short duration of follow-up.

A case-control study of diet and colon cancer was conducted in Argentina, where the usual diet is high in red meat (55). One hundred and ten casepatients were matched on age and sex with 220 neighborhood controls. Analysis of information on food consumption during the 5- year period ending 6 months before interview showed a highly protective effect of dietary fiber and some evidence for a protective effect of niacin. Total energy consumption increased relative risk by a factor of 1.84 per 1000 calories.

In a hospital- based study in northeastern Italy, subjects completed a questionnaire giving the frequency of consumption of specific food items before onset of the problem leading to the current hospitalization (56). Analysis of data for 123 cases of colon cancer, 125 cases of rectal cancer, and 699 controls revealed a protective effect for fiber- and vegetable-rich diets. Frequent consumption of refined starchy foods, eggs, cheese, or red meat was a risk factor. Some foods had differential effects on the odds ratios for colon and rectal cancer. For most subjects, a substantial proportion of dietary fiber was supplied by vegetables. Although the study could not determine whether risk was modified by fiber itself, a fiber component, a particular fiber type, or associated micronutrients, failure to find an association with fruit intake seems to argue  against a protective role for micrountrients such as vitamin C and β- carotene. Refined carbohydrate products, a risk factor in this study, comprised a larger fraction of the diet than they do in the USA. Somewhat different results were obtained from a hospitalbased case-control study in China, where the usual diet is quite unlike the usual Italian diet (57). Here, increased risk of colorectal cancer was associated with low intake of green vegetables, chives and celery, meat, eggs, grain, and soybean products. Results were similar but not identical for men and women and for colon and rectal cancer. The findings for meat were interesting in this population whose meat consumption is generally low. The greater risk associated with low meat consumption suggests that there is an optimal amount of meat, greater than zero, in a healthy diet.

A dietary study of hospitalized colorectal cancer patients in Majorca, with age-and sex-matched hospital and population controls, found that risk of colorectal cancer increases with increasing intake of total calories and cholesterol and decreases with increasing intake of pulses and folic acid (58). Of the three main components of total energy, protein (mainly animal) and carbohydrate were associated with risk; no significant effect of lipids or saturated fats was found.

Although adenomatous polyps are precursors of colorectal cancer, it is not known what proportion of colorectal cancers originate from such polyps or what proportion of polyps become cancerous. Furthermore, little is known about the etiology of adenomatous polyps beyond the fact that there is a genetic predisposition to them. An Australian case-control study tested the hypothesis  is that diet and alcohol consumption play a role in development of adenomatous colorectal polyps and that dietary risk factors are similar to those for colorectal cancer (59). Case and control groups had similar family histories of colorectal cancer. Subjects with adenomatous polyps had a significantly lower intake of fiber and vegetables than controls; men with polyps were also characterized by a higher intake of beef, milk, and beer. Results were less clear in a study of exercise, diet, and adenomatous polyps in Japanese self-defense officials (60). The men, mostly in their early 50s,were given a comprehensive retirement health examination (including a colonoscopy) and a self- administered questionnaire addressing dietary and other habits. Leisure time spent doing strenuous activities was inversely related to the risk of polyps, but dietary relationships were merely suggestive. A nonsignificant decrease in risk was associated with frequent consumption of rice, green tea, and instant coffee. No association was see for fruits, vegetables, meat, fish, or several other food items, In a Swedish study, low physical activity at work and in leisure time was associated with increased risk for colon but not rectal cancer (61). This study also found that frequent intake of meat, brown gravy, heavily browned fried meat, fish, and eggs was associated with increased colorectal cancer risk, as was high intake of fat or protein. A high intake of dietary fiber decreased risk at most colorectal sites.

A study in New York City of diet and the recurrence of colorectal adenomatous polyps found no associations for men (62).For women, however, significantly increased odds ratios were fund for high versus low quartiles of beef, cheese, total fat, and saturated fat consumption. Decreased odds ratios were associated with high fish, carbohydrate, and fiber consumption. Marginal effects were seen for total energy and vitamin A intake. Two ongoing studies are sharpening the focus on fiber’s role on the recurrence of adenomatous polyps (63). In one patients are taught a low-fat, high-fiber, high-fruit, high-vegetable dietary pattern after having polyps removed. In the other, similar subjects are given a high-fiber supplement but otherwise retain their customary dietary pattern. Together these studies should indicate whether the key is fiber or another dietary component or components. The response of men and women to modified diets may differ (64). After polypectomy, 201 subjects in Toronto were randomized to diet-counseling and control groups. After 12 months, fat consumption averaged 25% of energy in the counsel group and 33% in controls; fiber consumption was 35 and 16 g, respectively. Women who received counseling had a reduced rate of polyp recurrence, associated with reduced levels of serum cholesterol and fecal bile acids. Men, however, had an increased rate of recurrence, associated with decreased serum cholesterol but increased fecal bile acids.

Although a relationship between dietary fiber and development of cancers of the gastrointestinal tract seems fairly certain, the mechanisms and inter mediates involved are not well understood. Klurfeld reviewed carcinogenetic mechanisms mediated by dietary fiber (65). The role of fecal bile acids has been studied most extensively, but incongruities in human studies have not been resolved. Bacterial degradation of dietary fiber to short-chain fatty acids seems important, but the most readily fermentable fibers are no more protective than fibers refractive to fermentation. Promising topics for study include  physical characteristics of the feces, aqueous-phase bile acids, alterations in mucins,  mutagenicity of intestinal contents, changes in mucosal cytokinetics, enzyme activity (e.g., ornithine decarboxylase and aryl hydrocarbon hydroxylase). Neurogenic effects of bulk and short-chain fatty acids, local and systemic gut hormones and growth factors, transit time, pH , and availability of energy.

A large case-control study of dietary fiber and colorectal cancer conducted at SUNY – Buffalo added to the evidence for sex and site differences in response to fiber components (66). High intakes of total vegetable fiber, cellulose, hemicelluloses, and lignin were associated with increased risk of sigmoid colon cancer in women, but there was no association with risk at other subsites in women or at any site in men. The various fiver components appeared to have somewhat different effects in women, but strong correlations between the components made it difficult to analyze these results. This study could not draw any conclusions about cereal fiber, but a Swedish study did (67). A dietary survey of 41 colorectal cancer patients, 41 matched controls, and 801 hospital and population controls found that, per unit of energy, the habitual diet of cancer patients contained less cereal fiber (p<.001) as well as less riboflavin, calcium, and phosphorus.

Overall, cancer patients consumed more fat, protein, carbohydrate, and total energy and less cereal fiber than matched controls, but these differences were not statistically significant. High alcohol consumption was correlated with increased risk (p<.05). High intakes of calcium or cereal fiber, relative to energy, were associated with reduced risk of colon cancer; a similar association was found for intake of total fiber or cereal fiber and risk of rectal cancer.

One factor in the positive correlation between latitude and death rate from colon cancer may be intensity and duration of exposure to sunlight, with consequent effects on vitamin D and calcium metabolism. To investigate this, lavoratory, clinical, and epidemiologic studies were reviewed (68). Patterns of fat, fiber, fruit, and vegetable consumption do not readily explain the geographic pattern of colon- cancer mortality in the USA. However, at high latitudes, serum concentrations of vitamin D metabolites tend to be low and absorption of calcium may be poorer, especially in the elderly. Further, in animal studies, dietary supplementation with calcium and (or) vitamin D partly protects against colon tumors induced by a high-fat diet. All lines of evidence suggest to the authors that substantial reductions in rates of colon cancer could be achieved in many parts of the world by optimizing intake of calcium and vitamin D. The usual cautions regarding vitamin D toxicity are still warranted, and additional precautions are necessary for persons at risk for certain types of renal stones. Safe and effective ranges of calcium and vitamin D consumption for specific populations in the context of geography and culture need to be established worldwide.

A carefully reasoned review of admittedly meager data concluded that intestinal exposure to ingested iron may be an important determinant of colorectal cancer risk in humans (69). Iron has been associated with both initiation and promotion of tumors. Differences in intake of iron and promotion of tumors. Differences in intake of iron and substances such as phytate that affect its bioavailability may explain differences in colon-cancer risk between high – and low-risk countries and within the USA. The review touches on iron’s role in nutrition and metabolism; the complex system of iron absorption, transport, and storage that maintains adequate supplies while protecting against toxicity; the global nonproblem of iron deficiency if the root causes of anemia are controlled; the consequences of iron overload; and the rationale and experimental evidence for iron’s role in colorectal cancer.

The relationship between folate intake and risk of colorectal cancer was assessed  in a case –control study at SUNY – Buffalo (70). Again, a differential effect was seen according to site. While folate (controlled for total energy intake) was not consistently associated with colon cancer risk, risk of rectal cancer was reduced in the highest category of intake. For men in the highest quartile, the effect was highly significant (p<.001). The authors propose that the folate content of fruits and vegetables partly explains their protective effect. Folate has not been systematically studied in this regard, and in light of the depressed folate status in some segments of the U.S. population such investigations appear warranted.

Observations that ownership or use of a refrigerator reduces risk of gastric cancer were not initially extended to cancer at other sites. Another study form SUNY – Buffalo measured the magnitude of the “refrigerator effect” on cancers at other gastrointestinal sites (71). Case- patients were matched with age, sex-, and neighborhood-matched controls and interviewed regarding their usual diet, smoking and drinking history, and years of refrigerator ownership. No effects were found for cancer of the mouth or esophagus. For men but not women, refrigerator use was strongly protective against stomach cancer, weakly protective against colon cancer, and possibly weakly protective against real cancer.

diet and cancer

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OVERVIEW

The link between diet and cancer is firmly established in principle. Milner reviewed the information about nutrients and nonutrients whose effects on carcinogenesis have been verified, particularly those for which mechanisms of action can be explored (1). At same time he emphasized that the overall diet, not a single dietary component, is what can turn events toward or away from cancer. A corollary of this is that when cancer occurs, the dietary culprit is unlikely to be a contaminant or carcinogen taken out of the contest of  the total diet. This idea was underscored in a historical look at interest in the link between diet and cancer (2). According to traditional wisdom, malignancies arise from exposure to carcinogens, which were therefore the main target for research. But the list of chemical carcinogens grew so fast and so large that it became impossible to identify which ones pose a significant hazard, let alone to know what to do about it. Meanwhile, epidemiologists were proposing “life-style” hypotheses emphasizing dietary pattern. According to this line of thinking, the overall diet modulates the influence of a host of carcinogenic and anticarcinogenic  agents.

The proceedings of a conference on nutrition and cancer were published as a supplement to Cancer Research (3). Sessions at this conference were devoted to fats and energy, micronutrients and microconstituents, diet-associated carcinogens and mutagens, and mechanisms and risk assessment. In his keynote address, Doll spoke of the emergence of consensus among epidemiologists that diet might be responsible for 30-60% of cancers in developed countries-and that reduction of this effect would require decreasing consumption of fat, increasing require decreasing consumption of fat, increasing consumption of fruits, vegetables, fibers, and certain micronutrients, and perhaps improving methods of food preservation (4). He reviewed dietary trends and trends in cancer incidence and mortality, with examples for specific countries and cancer sites. His conclusions are encouraging : dietary changes that might reduce risk of fatal cancer by 20-60 % are practicable, and such changes have probably already contributed to recent reductions in the incidence of cancers of the stomach, colon, rectum, gallbladder, ovary, and endometrium. Participants in a panel discussion looked to future lines of inquiry that might be productive given the new perspective on diet and cancer (5).

A lively article highlighted some recent reviews of issues related o cancer and diet (6). The author rationalized the discrepant findings of a study linking meat consumption whit colon cancer in North American nurses and a case-control study in Japan that demonstrated an inverse relationship.  Other dietary and nondietary factors varied so greatly between studies that it was pointless to consider the results our of their context. Reviews of fiber,bcereals, sugar, and even hot peppers were touched on.

Another review discussed the mechanisms of neoplastic conversion and the subsequent growth and development of neplastic cells (7). Cancers of specific sites were considered in terms of mechanisms, geography, and nutritional traditions. One of a pair of complementary table summarized causes of cancer in North America: lifestyle (related to tobacco, diet, alcohol, sun, mycotoxin, and hepatitis B virus): transplacental chemicals; occupational; cryptogenic (viruses?); introgenic; multifactorial; and unspecified. The other listed specific actions that would promote health and lower risk of various chronic diseases.

In an important initative, the National Cancer Institute signed agreements with the Food and Drug Administration (FDA) and private companies and institutions to test foods for cancer prevention (8). The goal is to exploit the protective properties of natural phytochemicals by incorporating them into new fortified food products. The first studies will use fractions from citrus fruits, garlic, flaxseed, soybeans, and the parsley-carrot-celery family of vegetables. Later studies will be based on the most promising candidates from the initial groups plus cruciferous and solanaceous vegetables and combinations. Safety studies in animals will be followed by intervention trials in people at high risk for cancer. A positive outcome from these studies has been anticipated by several food companies that have already begun their own “designer food” projects. Meanwhile, epidemiologists from seven European countries have launched a prospective 5- year (or longer) dietary study in which more than 250,000 people will keep detailed food diaries and provide blood samples for analysis (9). In conjunction with this the effect of hormone replancement therapy will be studied in Great Britain.

It is important to know how the public perceive the role of dietary and other environmental factors in the causation and prevention of cancer, to maximize the impact of public health programs (10). A postal survey in South Australia revealed a relatively high degree of awareness and acceptance of lifestyle factors as determinants of cancer risk. This awareness extended with few differences to all sociodemographic groups. The roles of diet and  cigarettesmoking were widely recognized, but the importance of pollution of  the food supply was overestimated relative to nutrient imbalance. In this setting, the most effective public health efforts would most likely be ones directed at skill transfer and removal of barriers to change.

In discussing the future of nutrition research in cancer prevention, Greenwald first reviewed the role of specific dietary factors in cancer risk (11). He then described ongoing and proposed research programs, with emphasis on the extramural programs of the National Cancer Institute. Dietary guidelines developed by various organizations and government agencies were summarized. The author then identified gaps in knowledge, named some important areas for future research, and discussed changes in the food supply that have implications for health.

A volume in a series on nutrition dealt with the subject of vitamins and cancer prevention (12). The book is based on presentations at the Gladys Emerson Memorial symposium held at UCLA on 2-3 March 1989. Approaches range from basic laboratory research to clinical studies to preliminary studies of vitamin deficiency in cancer patients. Chapters address the role of specific vitamins in preventing or treating cancer and the mechanisms by which vitamins protect against  neoplasia. Of particular interest are discussions of folate, 1,25- dihydroxyvitamin D3 and coenzyme Q10 A conference at the National Institutes of Health, September 1990, was devoted to the biologic functions of ascorbic acid and its relation to cancer (13). Presentations considered vitamin C in relation to free radical scavenging, regulation of cellular and enzymatic function, the immune system, malignant transformation and growth of tumor cells, therapeutic applications, and dietary requirements.

Although a link between cancer and high consumption of red meat is frequently taken as proved, Kritchevsky’s review suggests that a cause – effect relationship is far from established (14). For example, in the USA between 1940 and 1970 per-capita meat consumption more than doubled, while cancer mortality was virtually unchanged. Further, risk of colon cancer did not show the socioeconomic gradient exhibited by meat consumption. Overall, 6 of 11 case – control studies of colon cancer found a positive association with meat consumption, 1 found a negative association, and 4 found none, Nor have epidemiologic studies of other types of cancer yielded convincing evidence that simply deleting beef (or meat) from the typical American diet would substantially reduce cancer risk. Having established this point, Kritchevskyreviewed animal and clinical studies of meat components specifically protein, fat, and cholesterol. Again, results are inconclusive and sometime surprising. Protein and fat may merely reflect the real culprit, affluence, which is manifested in excessive energy consumption and insufficient energy expenditure. Evidence for this is reviewed.

While evidence accumulates for a protective effect of wheat (15) and other fiber against cancer, the FDA has hesitated to allow health claims for fiber in nutrition labeling (16). Neverheless, they do endorse dietary guidelines recommending daily intake of 25 g of dietary fiber. While the distinction between health claims and dietary guidelines may be important in some circles, it should not obscure the message that fiber is a crucial constituent of a healthful diet.

A discussion of the “fat hypothesis” and cancer evaluated results of laboratory, clinical, and epidemiological studies (17). It concludes that although many lines of investigation converge upon fat as the main culprit in carcinogenesis, it is nearly impossible to control for the multitude of confounding factors. The authors believe that as the picture becomes more complex, more evidence points against the fat hypothesis than toward it. Further, they point out that after the key gene changes in carcinogenesis are known. Nutrition’s impact on the incidence and repair of DNA damage must still be understood.

Messina and Messina reviewed the use of soy foods and their potential role in cancer prevention (18). One of the sacred crops of ancient China, soybeans contain several substances with anticarcinogenic activity. Among these, protease inhibitors and phytic acid have traditionally been considered “antinutrients” but are beginning to be viewed in a positive light. Increasingly, the importance of nonnutrient phytochemicals is being recognized, and soybeans are rich in them.

A lead article in Science discusses possibilities for the primary prevention of cancer (19). We are at “the threshold of an era when many of the most prevalent human cancers can, to a significant extent, be prevented through lifestyle changes or medical interventions.” This bold statement is defended by a review of trends in incidence and mortality rates of major cancers and analysis of why these changes have occurred.