Multiplex genotyping of 1107 SNPs from 232 candidate genes identified an association between IL1A polymorphism and breast cancer risk.
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.
Han
Wonshik
W
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Kang
So Young
SY
Kang
Daehee
D
Park
Sue K
SK
Lee
Ji-Young
JY
Kim
Ho
H
Park
Ae Kyung
AK
Noh
Dong-Young
DY
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D053582:Interleukin-1alpha / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D053582:Interleukin-1alpha; D018799:Intercellular Adhesion Molecule-1