Breast cancer susceptibility alleles and ovarian cancer risk in two study populations

B81

Recent whole genome association studies have identified several novel risk alleles for breast cancer, including variants of the FGFR2, TNRC9, MAP3K1, and LSP1 genes. Given the role of hormones in the etiology of both breast and ovarian cancer and the shared association of these cancers with certain genetic variants, most notably mutations of the BRCA1 and BRCA2 genes, we examined the association between these novel breast cancer susceptibility alleles and ovarian cancer risk in two large study populations. Our analysis included 1,173 cases and 1,201 controls from a New England-based case-control study of ovarian cancer and 210 cases and 603 controls from the prospective Nurses’ Health Study. We genotyped six single nucleotide polymorphisms that were identified as breast cancer risk factors in two whole genome scans: rs1219648, rs2981582, rs3803662, rs889312, rs3817198, and rs13281615. We used logistic regression to estimate the relative risk (RR) of ovarian cancer for individuals heterozygous or homozygous for the minor allele at each locus, compared to individuals with the wild-type genotype. We also tested for heterogeneity in the results and pooled the estimates from the two study populations using a random effects model. There was no clear association between these six polymorphisms and ovarian cancer risk in either study population or in the pooled analysis. In analyses adjusted for the matching factors only, the pooled RRs for individuals heterozygous or homozygous for the minor allele were 1.12 (95% confidence interval [CI] 0.96-1.31) for rs1219648 (FGFR2), 1.13 (95% CI 0.97-1.32) for rs2981582 (FGFR2), 0.95 (95% CI 0.82-1.10) for rs3803662 (TNRC9), 1.01 (95% CI 0.87-1.17) for rs889312 (MAP3K1), 0.95 (95% CI 0.82-1.10) for rs3817198 (LSP1), and 1.02 (95% CI 0.87-1.19) for rs13281615 (chromosome 8q). Individuals heterozygous for the rs2981582 minor allele had a borderline significant increase in ovarian cancer risk in the pooled analysis (RR=1.17, 95% CI 0.99-1.38), but there was no evidence of a trend with increasing number of minor alleles (p-trend=0.52). There was also no clear evidence of an association between these polymorphisms and risk of the major histologic subtypes of ovarian cancer. These results do not provide strong support for an association between these six breast cancer susceptibility alleles and ovarian cancer risk.