title: Obesity and genetic polymorphism of ERCC2 and ERCC4 as modifiers of risk of breast cancer.
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 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 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/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.
authors.affiliation: Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 110-749, Korea.
authors.forename: Sang-Ah
authors.initials: SA
authors.lastname: Lee
authors.forename: Kyoung-Mu
authors.initials: KM
authors.lastname: Lee
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
authors.forename: Bongcheol
authors.initials: B
authors.lastname: Kim
authors.forename: Jinwu
authors.initials: J
authors.lastname: Nam
authors.forename: Keun-Young
authors.initials: KY
authors.lastname: Yoo
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
authors.forename: Sei-Hyun
authors.initials: SH
authors.lastname: Ahn
authors.forename: Ari
authors.initials: A
authors.lastname: Hirvonen
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007723:Korea; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D011110:Polymorphism, Genetic; D014157:Transcription Factors / Q000235:genetics*; D051759:Xeroderma Pigmentosum Group D Protein
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; C095888:xeroderma pigmentosum group F protein; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human