Candidate gene approach evaluates associations between OR10J3, FCER1A genes and breast cancer risk

1930 Purpose: This study was conducted to evaluate of common variation in candidate genes of breast cancer risk in Korean.\u2028 Methods: An Illumina GoldenGate assay was used to genotype1,536 common variants and near 205 genes in 209 cases and 209 controls in Korea. All SNPs chosen for this platform were drawn from the innate immunity-related genes as previously evaluated in relation to cancer risk or those with evidence for functional significance. We performed gene-based and SNPs based tests evaluating the robustness of our results with FDR and Permutation methods.\u2028 Results: Gene-based and SNP-based analyses showed promising associations with breast cancer risk for 23 genes: OR10J3, FCER1A, NCF4, CNTNAP1, CTNNB1, KLKB1, ITGB2, ALOX12B, KLK2, IRAK3, KLK4, STAT6, NCF2, CCL1, C1QR1, DEFB1, DLG5, ICAM1, C6, CCR6, TNFSF9, MBP, NOS1. The most significant association with breast cancer risk according to gene-based analyses was observed for the OR10J3 gene. Gene-based analyses firstly showed a significant finding in OR10J3 (p for likelihood ratio test, 1 degrees of freedom (df) =2×10-5). The FDR-adjusted p-value for the association of OR10J3 with breast cancer risk was also significant (global p =0.008 (1 df), p =0.02 (2 df)). Secondly, individual SNP-based analyses were quite concordant with gene-based analyses. Consistent with individual SNP analyses, haplotype analyses revealed two genes (OR10J3, FCER1A) were also strongly associated with reduced risk for breast cancer (global p=2×10-4, p=0.004 respectively). These two SNPs were adjacently located in chromosome 1q23 which was yet well unknown the functional association with breast cancer risk.\u2028 Conclusion: Through the highly multiplexed technology, candidate cancer genes and SNPs of OR10J3 and FCER1A have identified the association with breast cancer risks. Further second stage studies are required to confirm these findings, as well as to examine the biological mechanisms for the associations.