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.
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.
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.
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.
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).