TY - JOUR
T1 - Selected genetic polymorphisms in MGMT, XRCC1, XPD, and XRCC3 and risk of head and neck cancer
T2 - A pooled analysis
AU - Huang, Wen Yi
AU - Olshan, Andrew F.
AU - Schwartz, Stephen M.
AU - Berndt, Sonja I.
AU - Chen, Chu
AU - Llaca, Victor
AU - Chanock, Stephen J.
AU - Fraumeni, Joseph F.
AU - Hayes, Richard B.
PY - 2005/7
Y1 - 2005/7
N2 - Tobacco and alcohol consumption are the major risk factors for head and neck cancer, likely due to DNA-damaging processes. Genetic variations in DNA repair genes may affect an individual's susceptibility to head and neck cancer. Pooling data and DNA specimens from three case-control studies in western Washington State, North Carolina, and Puerto Rico, totaling 555 cases (430 whites) and 792 controls (695 whites), we studied the risk of head and neck cancer in relation to common nonsynonymous single-nucleotide polymorphisms in four DNA repair genes: MGMT (Leu84Phe and Ile143Val), XRCC1 (Arg399Gln), XPD (Lys751Gln), and XRCC3 (Thr 241Met). All single-nucleotide polymorphisms were assayed in a single laboratory. Among whites, carriage of the MGMT PHe84 [odds ratio (OR), 0.71; 95% confidence interval (95% CI), 0.51-0.98] or Val143 (OR, 0.66; 95% CI, 0.47-0.92) allele was associated with a decreased risk of head and neck cancer; the haplotype distribution for MGMT differed significantly between cases and controls (covariate-adjusted global permutation test, P = 0.012). The XRCC1 GlnGln399 genotype was also associated with decreased risk among whites (OR, 0.56; 95% CI, 0.32-0.94), whereas XPD 751 and XRCCS241 were not associated with risk. Alcohol-related risks tended to vary with DNA repair genotypes, especially for MGMT variants, whereas no effect modification was noted with tobacco use. Consistent findings from three case-control studies suggest that selected DNA repair enzymes may play a role in head and neck carcinogenesis.
AB - Tobacco and alcohol consumption are the major risk factors for head and neck cancer, likely due to DNA-damaging processes. Genetic variations in DNA repair genes may affect an individual's susceptibility to head and neck cancer. Pooling data and DNA specimens from three case-control studies in western Washington State, North Carolina, and Puerto Rico, totaling 555 cases (430 whites) and 792 controls (695 whites), we studied the risk of head and neck cancer in relation to common nonsynonymous single-nucleotide polymorphisms in four DNA repair genes: MGMT (Leu84Phe and Ile143Val), XRCC1 (Arg399Gln), XPD (Lys751Gln), and XRCC3 (Thr 241Met). All single-nucleotide polymorphisms were assayed in a single laboratory. Among whites, carriage of the MGMT PHe84 [odds ratio (OR), 0.71; 95% confidence interval (95% CI), 0.51-0.98] or Val143 (OR, 0.66; 95% CI, 0.47-0.92) allele was associated with a decreased risk of head and neck cancer; the haplotype distribution for MGMT differed significantly between cases and controls (covariate-adjusted global permutation test, P = 0.012). The XRCC1 GlnGln399 genotype was also associated with decreased risk among whites (OR, 0.56; 95% CI, 0.32-0.94), whereas XPD 751 and XRCCS241 were not associated with risk. Alcohol-related risks tended to vary with DNA repair genotypes, especially for MGMT variants, whereas no effect modification was noted with tobacco use. Consistent findings from three case-control studies suggest that selected DNA repair enzymes may play a role in head and neck carcinogenesis.
UR - http://www.scopus.com/inward/record.url?scp=22244454052&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=22244454052&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-05-0162
DO - 10.1158/1055-9965.EPI-05-0162
M3 - Article
C2 - 16030112
AN - SCOPUS:22244454052
SN - 1055-9965
VL - 14
SP - 1747
EP - 1753
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 7
ER -