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.