Association of Vitamin A and carotenoid intake with ovarian cancer risk

493 Oxidative stress and inflammation during ovulation may explain the increased ovarian cancer risk associated with nulliparity and ‘incessant ovulation’. We hypothesize that dietary components that possess antioxidant and DNA repair properties will protect the ovaries from oxidative damage and reduce the risk of ovarian cancer. While a few studies have examined the relation of antioxidant intake to the risk of ovarian cancer, the results are inconclusive. Questions still remain regarding the effects of confounding factors, such as menopause, smoking and drinking status, to the association of antioxidants with ovarian cancer development. We used data from a multiethnic, population-based case-control study, conducted between 1993-1999 in Hawaii and in Los Angeles, to examine the association of the consumption of micronutrients from foods and supplements with the risk of ovarian cancer. A structured questionnaire was administered to 558 histologically-confirmed epithelial ovarian cancer cases and 607 population controls. Overall, Vitamin A, α-and β-carotene intake was modestly associated with a reduced risk of ovarian cancer. A significant inverse gradient in ovarian cancer risk with increasing dietary intake of vitamin A or β-carotene intake was limited to never alcohol drinkers, ever smokers, and women with mucinous histological types of cancer. However, a significant positive trend in risk associated with dietary β-cryptoxanthin intake was observed for non-mucinous tumors, ever alcohol drinkers, and never smokers. The intake of other carotenoids and antioxidants, either from foods or supplements, was unrelated to ovarian cancer risk. Retinoic acid (RA) metabolic enzyme (i.e. alcohol dehydrogenase) activity and RA receptor gene profile may modulate the growth regulation function of vitamin A, which may provide a plausible link to our findings regarding the drinking and histologic-specific association, respectively. In addition, smoking exposures may induce a reactive oxygen species mediated apoptosis function of vitamin A, which could explain why high consumption of vitamin A was more beneficial for ever smokers than never smokers. Our data indirectly suggests that the apoptosis mechanism and retinoic acid metabolic pathway may play an important role in antiproliferative effects of vitamin A and β-carotene.