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.

Keyword

body mass index; breast neoplasms; DNA repair enzymes; ERCC4 protein
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