Exp Mol Med.
2005 Apr;37(2):86-90.
Obesity and genetic polymorphism of ERCC2 and ERCC4 as modifiers of risk of breast cancer
- Affiliations
-
- 1Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea. dhkang@snu.ac.kr
- 2Department of Biochemistry, Seoul National University College of Medicine, Seoul, Korea.
- 3Department of General Surgery, Seoul National University College of Medicine, Seoul, Korea.
- 4Pan Genomics Co., Ltd., Seoul, Korea.
- 5Department of Surgery, Ulsan University College of Medicine, Seoul, Korea.
- 6Department of Industrial Hygiene and Toxicology, Institute of Occupational Health 00250 Helsinki, Finland.
Abstract
- To evaluate the relationship of genetic polymorphisms of ERCC2 and ERCC4 genes, both involved in nucleotide excision repair (NER), and the risk of breast cancer, a hospital-based case-control study was conducted in Korea. Histologically confirmed breast cancer cases (n=574) and controls (n=502) with no present or previous history of cancer were recruited from three teaching hospitals in Seoul during 1995-2001. Information on selected characteristics was collected by interviewed questionnaire. ERCC2 Asp312Asn (G>A) was genotyped by single-base extension assay and ERCC4 Ser835Ser (T>C) by dynamic allele-specific hybridization system. Although no significant association was observed between the genetic polymorphisms and the risk of breast cancer, women with both ERCC2 A allele- and ERCC4 C allele-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 increased 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/m2) with a borderline significance. Our finding suggests that the combined effect of ERCC2 Asp312Asn and ERCC4 Ser835Ser genotypes might be associated with breast cancer risk in Korean women.
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