title: Genotype-phenotype relationship between DNA repair gene genetic polymorphisms and DNA repair capacity.
abstract: Genotype-phenotype relationships between genetic polymorphisms of DNA repair genes and DNA repair capacity were evaluated in a case-control study of breast cancer. Selected DNA repair genes included were those involved in double-strand break repair (ATM, XRCC2, XRCC4, XRCC6, LIG4, RAD51, RAD52), base excision repair (LIG1), nucleotide excision repair (ERCC1), and mismatch repair (hMLH1). The subjects consisted of histologically confirmed breast cancer cases (n=132) and controls (n=75) with no present or previous history of cancer. Seventeen single nucleotide polymorphisms of 10 genes (ATM -5144A>T, IVS21+1049T>C, IVS33-55T>C, IVS34+60G>A, and 3393T>G, XRCC2 31479G/A, XRCC4 921G/T, XRCC6 1796G/T, LIG4 1977T/C, RAD51 135G/C, 172G/T, RAD52 2259C/T, LIG1 583A/C, ERCC1 8092A/C, 354C/T, hMLH1 5' region -93G/A, 655A/G) were determined by TaqMan assay (ATM) or MALDI-TOF (all other genes). DNA repair capacity was measured by a host cell reactivation assay of repair of ultraviolet damage. The DNA repair capacity (%) did not differ between cases (median 37.2, interquartile range: 23.6-59.6) and controls (median 32.7, interquartile range: 26.7-53.2). However, DNA repair capacity significantly differed by the genotypes of ATM and RAD51 genes among cancer-free controls. Our findings suggest that DNA repair capacity might be influenced by genetic polymorphisms of DNA damage response genes and DNA repair genes.
authors.affiliation: Division of Cancer Prevention, National Cancer Control Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do, Korea.
authors.forename: Aesun
authors.initials: A
authors.lastname: Shin
authors.forename: Kyoung-Mu
authors.initials: KM
authors.lastname: Lee
authors.forename: Byungchan
authors.initials: B
authors.lastname: Ahn
authors.forename: Chung-Gyu
authors.initials: CG
authors.lastname: Park
authors.forename: Sue-Kyung
authors.initials: SK
authors.lastname: Noh
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Park
authors.forename: Sei-Hyun
authors.initials: SH
authors.lastname: Ahn
authors.forename: Keun-Young
authors.initials: KY
authors.lastname: Yoo
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
mesh_terms: D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005838:Genotype; D006801:Humans; D015994:Incidence; D007723:Korea; D016014:Linear Models; D010641:Phenotype; D011110:Polymorphism, Genetic; D011336:Probability; D011379:Prognosis; D051135:Rad51 Recombinase / Q000235:genetics; D051721:Rad52 DNA Repair and Recombination Protein / Q000235:genetics; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D016019:Survival Analysis
chemical_list: D004268:DNA-Binding Proteins; C497194:RAD52 protein, human; D051721:Rad52 DNA Repair and Recombination Protein; C101467:XRCC4 protein, human; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D045643:DNA Repair Enzymes