Circulating 25-hydroxyvitamin D and risk of epithelial ovarian cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers

Abstract

A role for vitamin D in ovarian cancer etiology is supported by ecologic studies of sunlight exposure, experimental mechanism studies, and some studies of dietary vitamin D intake and genetic polymorphisms in the vitamin D receptor. However, few studies have examined the association of circulating 25-hydroxyvitamin D (25(OH)D), an integrated measure of vitamin D status, with ovarian cancer risk. A nested case-control study was conducted among 7 prospective studies to evaluate the circulating 25(OH)D concentration in relation to epithelial ovarian cancer risk. Logistic regression models were used to estimate odds ratios and 95% confidence intervals among 516 cases and 770 matched controls. Compared with 25(OH)D concentrations of 50-<75 nmol/L, no statistically significant associations were observed for <37.5 (odds ratio (OR) = 1.21, 95% confidence interval (CI): 0.87, 1.70), 37.5-<50 (OR = 1.03, 95% CI: 0.75, 1.41), or > or =75 (OR = 1.11, 95% CI: 0.79, 1.55) nmol/L. Analyses stratified by tumor subtype, age, body mass index, and other variables were generally null but suggested an inverse association between 25(OH)D and ovarian cancer risk among women with a body mass index of > or =25 kg/m(2) (P(interaction) < 0.01). In conclusion, this large pooled analysis did not support an overall association between circulating 25(OH)D and ovarian cancer risk, except possibly among overweight women.

Figure 1.

Forest plots for the meta-analysis of the association between circulating 25-hydroxyvitamin D (25(OH)D) and risk of ovarian cancer within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Risk estimates, by cohort, for subjects with circulating 25(OH)D concentrations <25 nmol/L (A) and ≥75 nmol/L (B) are compared with the referent group (50–<75 nmol/L). Odds ratios and 95% confidence intervals were derived from conditional logistic regression models adjusted for duration of oral contraceptive use and number of pregnancies. Cases and controls were matched on age (±1 year), race/ethnicity (white, black, Asian, other), date of blood draw (±30 days), and study cohort, except for the Nurses’ Health Study, which was matched on age (±1 year), month of blood collection (±1 month), time of day of blood draw (±2 hours), fasting status, menopausal status, and postmenopausal hormone use at blood draw. The black squares show the odds ratios, the bars show the 95% confidence intervals, and the size of each square is inversely proportional to the variance of the log odds ratio estimate in each cohort. The overall estimates (diamonds) come from a meta-analysis using random-effects modeling. CPS-II and SWHS data are not included in the highest versus referent category forest plot (B) because of unstable risk estimates due to small numbers. CI, confidence interval; CPS-II, Cancer Prevention Study II Nutrition Cohort; MEC, Multiethnic Cohort Study; NHS, Nurses’ Health Study; NYU-WHS, New York University Women's Health Study; OR, odds ratio; PLCO, Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; SWHS, Shanghai Women's Health Study; WHS, Women's Health Study.