Potentially functional single nucleotide polymorphisms in the core nucleotide excision repair genes and risk of squamous cell carcinoma of the head and neck.
Susceptibility to cancer has been associated with DNA repair capacity, a global reflection of all functional variants, most of which are relatively rare. Among the 1,098 single nucleotide polymorphisms (SNP) identified in the eight core nucleotide excision repair genes, only a few are common nonsynonymous or regulatory SNPs that are potentially functional. We tested the hypothesis that seven selected common nonsynonymous and regulatory variants in the nucleotide excision repair core genes are associated with risk of squamous cell carcinoma of the head and neck (SCCHN) in a hospital-based, case-control study of 829 SCCHN cases and 854 cancer-free controls. Assuming a recessive genetic model, we found that only carriers of the XPC 499Val/Val genotype had a significantly increased SCCHN risk (adjusted odds ratio, 1.65; 95% confidence interval, 1.16-2.36). In analysis of the joint effects, the number of observed risk genotypes was associated with SCCHN risk in a dose-response manner (P for trend = 0.017) and those who carried four or more risk genotypes exhibited a borderline significant 1.23-fold increased SCCHN risk (adjusted odds ratio, 1.23; 95% confidence interval, 0.99-1.53). In the stratified analysis, the dichotomized combined effect of the seven SNPs was slightly more evident among older subjects, women, and laryngeal cancer. These findings suggest that these potentially functional SNPs may collectively contribute to susceptibility to SCCHN. These findings need to be validated in larger, independent studies.
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Unit 1365, 1155 Pressler, Houston, TX 77030, USA.
Jiaze
J
An
Zhensheng
Z
Liu
Zhibin
Z
Hu
Guojun
G
Li
Li-E
LE
Wang
Erich M
EM
Sturgis
Adel K
AK
El-Naggar
Margaret R
MR
Spitz
Qingyi
Q
Wei
D000367:Age Factors; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012737:Sex Factors; D011503:Transglutaminases / Q000235:genetics; D014633:Valine / Q000235:genetics
D004268:DNA-Binding Proteins; C086984:XPC protein, human; D011503:Transglutaminases; D014633:Valine