The XRCC1 399 glutamine allele is a risk factor for adenocarcinoma of the lung

Citation
Kk. Divine et al., The XRCC1 399 glutamine allele is a risk factor for adenocarcinoma of the lung, MUT R-DNA R, 461(4), 2001, pp. 273-278
Citations number
28
Categorie Soggetti
Molecular Biology & Genetics
Journal title
MUTATION RESEARCH-DNA REPAIR
ISSN journal
09218777 → ACNP
Volume
461
Issue
4
Year of publication
2001
Pages
273 - 278
Database
ISI
SICI code
0921-8777(20010105)461:4<273:TX3GAI>2.0.ZU;2-I
Abstract
Defects in the repair and maintenance of DNA increase risk for cancer. X-ra y cross-complementing group 1 protein (XRCC1) is involved with the repair o f DNA single-strand breaks. A nucleotide substitution of guanine to adenine leading to a non-conservative amino acid change was identified in the XRCC 1 gene at codon 399 (Arg/Gln), This change is associated with higher levels of aflatoxin Bl-adducts and glycophorin A somatic mutations. A case-contro l study was conducted to test the hypothesis that the 399Gln allele is posi tively associated with risk for adenocarcinoma of the lung. XRCC1 genotypes were assessed at codon 399 in 172 cases of lung adenocarcinoma and 143 can cer-free controls. Two ethnic populations were represented, non-Hispanic Wh ite and Hispanic. The distribution of XRCC1 genotypes differed between case s and controls. Among cases, 47.7% were Arg/Arg, 35.5% were Arg/Gln. and 16 .9% were Gln/Gln. Among controls, XRCC1 allele frequencies were 45.5% for A rg/Arg, 44.8% for Arg/Gln, and 9.8% for Gln/Gln. Logistic regression analys is was used to assess the association between lung adenocarcinoma and the G /G genotype relative to the A/A or A/G genotypes. In non-Hispanic White par ticipants, the lung cancer risk associated with the G/G genotype increased significantly after adjustment for age (OR = 2.81; 95% CI, 1.2-7.9; P = 0.0 3) and increased further after adjustment for smoking (OR = 3.25;95% CI, 1. 2-10.7; P = 0.03). Among all groups, a significant association was found be tween the G/G homozygote and lung cancer(OR = 2.45; 95% CI, 1.1-5.8: P = 0. 03) after adjustment for age, ethnicity, and smoking. This study links a fu nctional polymorphism in the critical repair gene XRCC1 to risk for adenoca rcinoma of the lung. (C) 2001 Elsevier Science B.V, All rights reserved.