Vitamin D receptor rs2228570 polymorphism and invasive ovarian carcinoma risk: pooled analysis in five studies within the Ovarian Cancer Association Consortium

Abstract

The association of invasive ovarian carcinoma risk with the functional polymorphism rs2228570 (aka rs10735810; FokI polymorphism) in the vitamin D receptor (VDR) gene was examined in 1820 white non-Hispanic cases and 3479 controls in a pooled analysis of five population-based case-control studies within the Ovarian Cancer Association Consortium. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Carriers of the rare T allele were at increased risk of ovarian carcinoma compared to women with the CC genotype in all studies combined; each copy of the T allele was associated with a modest 9% increased risk (OR = 1.09; 95% CI: 1.01-1.19; p = 0.04). No significant heterogeneity among studies was observed (p = 0.37) and, after excluding the dataset from the Hawaii study, the risk association for rs2228570 among replication studies was unchanged (OR = 1.09; 95% CI: 1.00-1.19; p = 0.06). A stronger association of rs2228570 with risk was observed among younger women (aged < 50 years versus 50 years or older) (p = 0.04). In all studies combined, the increased risk per copy of the T allele among younger women was 24% (OR = 1.24; 95% CI: 1.04-1.47; p = 0.02). This association remained statistically significant after excluding the Hawaii data (OR = 1.20; 95% CI: 1.01-1.43; p = 0.04). No heterogeneity of the association was observed by stage (p = 0.46), tumor histology (p = 0.98), or time between diagnosis and interview (p = 0.94). This pooled analysis provides further evidence that the VDR rs2228570 polymorphism might influence ovarian cancer susceptibility.

Figure 1

Forest plot of the ORs and 95% Cls comparing invasive ovarian carcinoma risk among women < 50 years of age associated with the VDR rs2228570 rare allele homozygotes (TT genotype) versus common allele homozygotes (CC genotype) for 4 studies included in the current pooled analysis (UKOPS study participants were excluded because all were >50 years of age). The summary OR=1.47; 95% Cl: 1.02–2.12; p=0.04.

Figure 2

Forest plot of the ORs and 95% Cls comparing ovarian carcinoma risk for the VDR rs2228570 rare allele homozygotes (TT genotype) versus common allele homozygotes (CC genotype) for 5 studies included in the current pooled analysis (HAW, MALOVA, SEARCH, GEOCS, UKOPS) and published reports by Tworoger et al. (NHS I and II, WHS, and NECC studies) and Clendenen et al. The summary OR=1.20; 95% Cl:1.05–1.38; p=0.009.