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We sought to identify genes and polymorphisms associated with breast cancer risk among Korean women using multiplex genotyping. The SNPs (n=1536) of 264 candidate genes were genotyped using the Illumina Golden Gate assay. These genes are involved in the pathways controlling apoptosis/anti-apoptosis, the immune and inflammatory responses, cytokines, DNA repair, cell adhesion, and cell cycle/proliferation. Breast cancer cases (n=209) were recruited from Seoul National University Hospital. Age-matched control subjects (n=209) were selected from a health examinees cohort. Gene-based and SNP-based tests were performed. The final analysis includes 117 cases and 164 controls with 1107 SNPs in 232 genes. Gene-based analyses showed that IL1A, TNFRSF10B, TNFRSF1B, ICAM, and TNFSF9 were significantly associated with breast cancer risk (p<0.01). IL1A was the most significant gene associated with breast cancer risk [p for likelihood ratio test, 1 degree of freedom (df)=6x10(-7); FDR-adjusted p-value, 1df=4x10(-4), 2df=0.0071, respectively]. Individual SNP-based analyses revealed that the rare allele of the IL1A SNP rs2856836, Ex7-592Tright curved arrow C, was strongly associated with breast cancer risk (FDR-adjusted p-value, 1df=0.0027, 2df=0.0162). This SNP was found to increase risk for breast cancer [odds ratio (OR)=2.88, 95% confidence interval (CI)=1.58-5.27 for heterozygote and OR=8.17, 95% CI=2.23-29.99 for rare homozygote]. In summary, we identified a common genetic variant in IL1A strongly associated with breast cancer risk.

Multiplex genotyping of 1107 SNPs from 232 candidate genes identified an association between IL1A polymorphism and breast cancer risk.