rs1219648

Based on a study of ~2500 female patients of European ancestry with sporadic postmenopausal breast cancer, this SNP in the FGFR2 showed the greatest risk. The risk allele is rs1219648(G), with a pooled odds ratio of 1.64 (CI:1.42-1.90) for rs1219648(G;G) homozygotes, and an odds ratio of 1.20 (CI: 1.07-1.42) for rs1219648(A;G) heterozygotes, compared with rs1219648(A;A) homozygotes. rs1219648 represents the SNP in the FGFR2 gene with the strongest association with breast cancer. However, nearby SNPs are almost as predictive. In particular, the following SNP alleles all have linkage values of 0.96 or greater with the rs1219648(G) allele in European populations: *rs2981579(A) *rs2420946(T) *rs11200014(A) An experimental rationale is presented indicating that this SNP is part of a haplotype that increases risk for ER+ breast cancer by increasing FGFR2 transcription. rs1219648 is not associated with endometriosis risk. rs1219648 may account for a substantial fraction of breast cancer in Arab (12%), Ashkenazi (15%), and Sephardi Jewish (22%) populations. Based on a study of 1,049 Chinese breast cancer patients, carriers of risk alleles at three SNPs (rs2981582, rs1219648 and rs2420946) were at 1.36x increased risk for breast cancer (CI: 1.13-1.62, p = 0.001). A study of 1,173 Caucasian ovarian cancer patients did not find strong support for an association with rs1219648. A study of 1,225 Caucasian breast cancer patients found a significant association between rs1219648 but only in women with estrogen receptor positive (ER+), progesterone receptor positive (PR+) and HER2/Neu negative (HER2-) tumors. An interaction was also observed between combined hormone replacement therapy use and rs1219648 genotypes on breast cancer risk in Caucasian women (p = 0.010).