title: Polymorphisms in the DNA repair genes XPD, XRCC1, XRCC3, and APE/ref-1, and the risk of lung cancer among male smokers in Finland.
abstract: Associations between lung cancer risk and common polymorphisms in the DNA repair genes xeroderma pigmentosum complementation group D (XPD), X-ray repair cross-complementing group 1 (XRCC1), XRCC3 and apurinic/apyrimidinic endonuclease/redox factor 1 were examined within a randomized clinical trial designed to determine whether alpha-tocopherol, beta-carotene, or both would reduce cancer incidence among male smokers in Finland. We found no direct association between lung cancer risk and any of the DNA repair genotypes studied, however, the association between XPD codon 751 genotype and lung cancer was modified by alpha-tocopherol supplementation, and the association between XRCC1 codon 399 genotype and lung cancer was modified by the amount of smoking. Our results suggest that common alterations in single DNA repair genes are not major determinants of lung cancer susceptibility among smokers.
authors.affiliation: Cancer Prevention Studies Branch, Center for Cancer Research, National Cancer Institute, 6116 Executive Boulevard, Suite 700, Bethesda, MD 20892-7058, USA. misrar@ctep.nci.nih.gov
authors.forename: R Rita
authors.initials: RR
authors.lastname: Misra
authors.forename: Duminda
authors.initials: D
authors.lastname: Ratnasinghe
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Tangrea
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.forename: Mark R
authors.initials: MR
authors.lastname: Andersen
authors.forename: Michael
authors.initials: M
authors.lastname: Barrett
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
mesh_terms: D000368:Aged; D019757:Carbon-Oxygen Lyases / Q000235:genetics*; D016022:Case-Control Studies; D004265:DNA Helicases; D004260:DNA Repair / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004268:DNA-Binding Proteins / Q000235:genetics*; D005387:Finland / Q000453:epidemiology; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology*; D014157:Transcription Factors; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein; D024502:alpha-Tocopherol / Q000097:blood / Q000627:therapeutic use; D019207:beta Carotene / Q000097:blood / Q000627:therapeutic use
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D011506:Proteins; D014157:Transcription Factors; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; D019207:beta Carotene; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; D019757:Carbon-Oxygen Lyases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; C497292:ERCC2 protein, human; D024502:alpha-Tocopherol