In this cohort of California teachers, we found little evidence that specific foods or nutrients, other than perhaps isoflavones, are associated with risk of ovarian cancer. Thus, our results extend the null findings of the pooled analysis of cohort studies, in which no association was observed between dietary factors and ovarian cancer risk (14
). The inverse association between consumption of isoflavones and risk of ovarian cancer is intriguing, because it can be explained by a cogent biologic mechanism. The preponderance of scientific evidence suggests that estrogens promote the development of ovarian cancer, possibly by stimulating the growth and proliferation of ovarian surface epithelial cells, which express estrogen and androgen receptors (44
). As a corollary, phytoestrogens may inhibit ovarian cancer development by decreasing endogenous estrogen levels through stimulation of sex-hormone binding globulin production by the liver, thereby decreasing the levels of bioavailable estrogens (46
); through competitive binding to estrogen receptors (47
); and/or through inhibition of the activity of aromatase, the enzyme responsible for conversion of androgens to estrogens (48
). Indeed, previous studies have shown that phytoestrogens inhibit the growth and proliferation of ovarian cancer cell lines (18
), although these effects may also be mediated through estrogen-independent pathways (17
). Two case-control studies found an inverse association between dietary intake of phytoestrogens (isoflavones or lignans) and ovarian cancer risk (49
). Because food frequency questionnaire assessment of dietary lignan intake was poorly correlated with measured urinary excretion of lignans in women in our cohort (29
), we did not examine the association between dietary lignan consumption and risk of ovarian cancer.
Although isothiocyanates, too, have antiestrogenic properties (20
), as well as antioxidant and detoxifying effects (19
), we did not observe any association between isothiocyanate consumption and risk of ovarian cancer. This result is consistent with the lack of association between cruciferous vegetable intake and ovarian cancer risk in previous case-control studies (2
). Moreover, we found no association between consumption of other antioxidant nutrients or indices of overall dietary antioxidant intake and risk of ovarian cancer. These results corroborate those from two other prospective cohorts in which there was no association between consumption of vitamin A, C, or E, carotenoids, or fruits and/or vegetables and risk of ovarian cancer (10
). Although findings of an inverse association between tea drinking and risk of ovarian cancer in a Swedish cohort (51
) and a Chinese case-control study (52
) were speculatively attributed to the antioxidant effects of polyphenols in tea, no such association with tea drinking—even at a comparable frequency—was observed in our study or those of others (53
). The discrepancy in results among studies may be due to cultural differences in the types of tea consumed, bias, or chance. In combination with the substantial evidence of no association between fruit and vegetable consumption and risk of ovarian cancer (10
), our findings do not substantiate a protective effect of dietary antioxidants against ovarian cancer development.
Despite the considerable strengths of our study, including its large size, prospective exposure assessment, and virtually complete case ascertainment, there are several limitations to consider. We assessed usual dietary intake only at one point in adulthood, and our study cohort has a broad age range; it could be that diet during some other age or time period or cumulative intake or change in dietary habits over time is more relevant to ovarian cancer risk. In addition, we tested many potential associations, and the observed inverse association with isoflavone intake—although hypothesized a priori—may have been due to chance. Conversely, the absence of any other significant associations with ovarian cancer risk could be due to a lack of sufficient statistical power to detect associations in our cohort.
Our study is also subject to the limitations of all observational studies of dietary intake. For instance, food frequency questionnaires have a limited capacity to capture detailed information about food and nutrient consumption (55
). However, misclassification in our cohort was likely to be nondifferential, because exposure information was collected prospectively; also, the food frequency questionnaire and nutrient database used in our study were thoroughly validated (23
). Another potential limitation is that the observed inverse association of ovarian cancer risk with intake of isoflavones, as well as the marginal positive associations with intake of antioxidant micronutrients, could be explained by other factors correlated with both dietary habits and ovarian cancer risk, such as socioeconomic status, although adjustment for a neighborhood-based measure of socioeconomic status did not impact our estimates. Similarly, the lack of other apparent associations could be due to confounding by uncontrolled or imperfectly adjusted factors.
Bearing these caveats in mind, we conclude that our study does not support a major role of diet in ovarian cancer development, at least in this predominantly (87 percent) non-Hispanic White cohort. High consumption of isoflavones may decrease ovarian cancer risk and may be partly responsible for the markedly lower incidence rates of ovarian cancer in Asian populations (including natives and migrants), among whom dietary intake of soy products is typically high, than in Western populations, whose soy intake is generally low (1
). However, international and racial/ethnic discrepancies in ovarian cancer incidence could also be explained by other environmental and genetic differences. Therefore, nondietary, potentially modifiable environmental differences must be ascertained and understood in order to identify feasible methods to prevent the development of ovarian cancer in the general population.