Candidate gene approach evaluates association between innate immunity genes and breast cancer risk in Korean women

Objectives: This study was conducted to investigate the role of common variation in innate immunity-related genes as susceptibility factors to breast cancer risk in Korean women. Methods: Total 1536 single-nucleotide polymorphisms (SNPs) in 203 genes were analyzed by Illumina GoldenGate assay in 209 cases and the same numbers of controls. Both SNP and gene-based tests were used to evaluate the association with breast cancer risk. The robustness of results was further evaluated with permutation method, false discovery rate and haplotype analyses. Results: Both SNP and gene-based analyses showed promising associations with breast cancer risk for 17 genes: OR10J3, FCER1A, NCF4, CNTNAP1, CTNNB1, KLKB1, ITGB2, ALOX12B, KLK2, IRAK3, KLK4, STAT6, NCF2, CCL1, C1QR1, MBP and NOS1. The most significant association with breast cancer risk was observed for the OR10J3 SNP (rs2494251, P-value = 1.2 x 10(-4)) and FCER1A SNP (rs7548864, P-value = 7.7 x 10(-4)). Gene-based permutation and false discovery rate P-values for OR10J3 SNP (rs2494251) with breast cancer risk were also significant (P = 4 x 10(-5) and 0.008, respectively). Haplotype analyses supported these findings that OR10J3 and FCER1A were most significantly associated with risk for breast cancer (P = 2 x 10(-4) and 0.004, respectively). Conclusion: This study suggests that common genetic variants in the OR10J3 and FCER1A be strongly associated with breast cancer risk among Korean women.Weidinger S, 2008, PLOS GENET, V4, DOI 10.1371/journal.pgen.1000166Han SH, 2008, BREAST CANCER RES TR, V110, P387, DOI 10.1007/s10549-007-9730-5Lee KM, 2007, BREAST CANCER RES TR, V106, P433, DOI 10.1007/s10549-007-9506-ySigurdson AJ, 2007, CANCER EPIDEM BIOMAR, V16, P2000, DOI 10.1158/1055-9965.EPI-07-0282Lee JH, 2007, J KOREAN MED SCI, V22, pS11Potaczek DP, 2007, ALLERGY, V62, P1095, DOI 10.1111/j.1398-9995.2007.01446.xBernig T, 2007, CARCINOGENESIS, V28, P828, DOI 10.1093/carcin/bgl198Garcia-Closas M, 2007, PLOS GENET, V3, P287, DOI 10.1371/journal.pgen.0030029Shaffer JP, 2007, BIOMETRICAL J, V49, P136, DOI 10.1002/bimj.200610297Potaczek DP, 2006, ALLERGY, V61, P1230, DOI 10.1111/j.1398-9995.2006.01195.xLee KM, 2006, BREAST CANCER RES TR, V96, P197, DOI 10.1007/s10549-005-9079-6Packer BR, 2006, NUCLEIC ACIDS RES, V34, pD617, DOI 10.1093/nar/gkj151Hefler LA, 2005, CLIN CANCER RES, V11, P5718, DOI 10.1158/1078-0432.CCR-05-0001Parkin DM, 2005, CA-CANCER J CLIN, V55, P74Mori K, 2004, CANCER RES, V64, P7464Thompson D, 2004, J MAMMARY GLAND BIOL, V9, P221Lin EY, 2004, BRIT J CANCER, V90, P2053, DOI 10.1038/sj.bjc.6601705Hasegawa M, 2003, J IMMUNOL, V171, P1927Ellies LG, 2003, INT J CANCER, V106, P1, DOI 10.1002/ijc.11178Sfondrini L, 2003, ENDOCR-RELAT CANCER, V10, P301Coussens LM, 2002, NATURE, V420, P860, DOI 10.1038/nature01322Curran JE, 2002, CANCER LETT, V188, P103Goode EL, 2002, CANCER EPIDEM BIOMAR, V11, P1513Shikanai T, 2002, J APPL PHYSIOL, V93, P37, DOI 10.1152/japplphysiol.00993.2001Shacter E, 2002, ONCOLOGY-NY, V16, P217KEY TJ, 2001, LANCET ONCOL, V2, P133LEWIS CE, 1995, J LEUKOCYTE BIOL, V57, P747DOMBROWICZ D, 1993, CELL, V75, P969