Obesity and genetic polymorphism of ERCC2 and ERCC4 as modifiers of risk of breast cancer

초록

To evaluate the relationship of genetic polymor-phisms of ERCC2 and ERCC4 genes, both in-volved in nucleotide excision repair (NER), and the risk of breast cancer, a hospital-based case-con-trol study was conducted in Korea. Histologically confirmed breast cancer cases (n = 574) and con-trols (n = 502) with no present or previous history of cancer were recruited from three teaching hos-pitals in Seoul during 1995-2001. Information on selected characteristics was collected by inter-viewed questionnaire. ERCC2 Asp 312 Asn (G ＞A) was genotyped by single-base extension assay and ERCC4 Ser 835 Ser (T ＞C) by dynamic allele-specific hybridization system. Although no signifi-cant association was observed between the gene-tic polymorphisms and the risk of breast cancer, women with both ERCC2 A allele- and ERCC4 Callele-containing genotypes showed a 2.6-fold risk (95% CI: 1.02-6.48) of breast cancer compared to women concurrently carrying the ERCC2 GG and ERCC4 TT genotypes. The breast cancer risk in-creased as the number of “at risk” genotypes increased with a borderline significance (P for trend = 0.07). Interactive effect was also observed between ERCC4 genotype and body mass idnex (BMI) for the breast cancer risk; the ERCC4 C allele containing genotypes posed a 1.7-fold (95% CI: 0.96-2.93) breast cancer risk in obese women (BMI ＞25 kg/m 2 ) with a borderline significance. Our finding suggests that the combined effect of ERCC2 Asp 312 Asn and ERCC4 Ser 835 Ser genotypes might be associated with breast cancer risk in Korean women.

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