Epidemiologic and laboratory studies support a role for the vitamin D endocrine system in ovarian carcinogenesis. The association of ovarian cancer risk with polymorphisms in the vitamin D receptor (VDR) gene, including rs10735810 (FokI), rs11568820 (Cdx-2), rs1544410 (BsmI), rs7975232 (ApaI), rs731236 (TaqI), and BsmI-ApaI-TaqI combined genotypes, was examined among 313 women with epithelial ovarian carcinoma and 574 controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression. The associations of VDR polymorphisms with risk were generally inconsistent across ethnic groups. Among Caucasian women (72 cases, 148 controls), heterozygous and homozygous ApaI A allele carriers were at increased ovarian carcinoma risk compared with homozygous carriers of the ApaI a allele (OR 2.8, 95% CI 1.2-7.0 and OR 3.4, 95% CI 1.3-9.1; P(trend) = 0.02). Caucasian heterozygous carriers of FokI f allele were also at increased risk of ovarian carcinoma compared with homozygous carriers of the common allele (OR 2.5, 95% CI 1.3-4.8; P(trend) = 0.04). Among Japanese women (94 cases, 173 controls), ovarian cancer risk was significantly decreased (OR 0.5, 95% CI 0.3-0.9) among Cdx-2 A allele heterozygotes compared with homozygote G allele carriers (P(trend) = 0.03). Compared with the bbaaTT BsmI-ApaI-TaqI genotype, bbaATT and BBAAtt genotypes were associated with increased ovarian cancer risk in Caucasian women (OR 4.2, 95% CI 1.3-13.1 and OR 5.2, 95% CI 1.6-17.5), but not in Japanese women (OR 1.1, 95% CI 0.6-1.9 and OR 2.3, 95% CI:0.4-12.3). This investigation provides some evidence that polymorphisms in the VDR gene might influence ovarian cancer susceptibility.