Carcinogenesis Advance Access originally published online on April 16, 2009
Carcinogenesis 2009 30(9):1528-1531; doi:10.1093/carcin/bgp084
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Candidate gene approach evaluates association between innate immunity genes and breast cancer risk in Korean women
1 Department of Preventive Medicine, Seoul National University College of Medicine, 103 Daehak-Ro, Jongno-Gu, Seoul 110-799, Korea
2 Department of Epidemiology and Biostatistics, School of Public Health, Seoul National University, 103 Daehak-Ro, Jongno-Gu, Seoul 110-460, Korea
3 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
4 Cancer Research Institute
5 Department of Surgery, Seoul National University College of Medicine, 103 Daehak-Ro, Jongno-Gu, Seoul 110-799, Korea
6 Department of Health and Human Services, Core Genotyping Facility at the Advanced Technology Center of the National Cancer Institute, Bethesda, MD, USA
7 Department of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology and College of Medicine, Seoul National University, Gwanak 599 Gwanak-ro, Gwanak-gu, Seoul 151–742, Korea
* To whom correspondence should be addressed. Tel: +82 2 740 8326; Fax: +82 2 747 4830; Email: dhkang{at}snu.ac.kr
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.
Abbreviations: CI, confidence interval; FDR, false discovery rate; LRT, likelihood ratio test; OR, odds ratio; SNP, single-nucleotide polymorphism
Received November 14, 2008; revised February 24, 2009; accepted April 4, 2009.