DNA repair gene XRCC2 and XRCC3 polymorphisms and susceptibility to cancers of the upper aerodigestive tract.
Cigarette smoke can generate reactive oxygen species, which are capable of inducing double-strand breaks (DSBs) in DNA. Polymorphisms in XRCC2 and XRCC3 genes, involved in DSBs repair pathways, may alter an individual's susceptibility to smoking-related cancers. We investigated the effect of XRCC2 Arg(188)His and XRCC3 Thr(241)Met polymorphisms in cancer proneness in 121 oral/pharynx cancer cases, 129 larynx cancer cases and 172 noncancer controls, all Caucasian smokers. The XRCC2 His-allele was associated with a significantly increased risk of pharyngeal cancer (OR=2.9, 95% CI: 1.3-6.2). No significant associations were observed between the XRCC3 Thr(241)Met polymorphism and overall risk of developing UADT cancers. However, quite opposite to the expectations, a reduced risk of supraglottic cancer was found for carriers of the XRCC3 Met variant allele (OR=0.3, 95% CI: 0.2-0.7). These findings provide evidence for the view that polymorphisms in DNA repair genes may modify individual susceptibility to smoking-related cancers.
Benhamou
Simone
S
INSERM and Evry University, EMI 00-06, Statistical Methods and Genetic Epidemiology of Multifactorial Diseases, Evry, France. benhamou@evry.inserm.fr
Tuimala
Jarno
J
Bouchardy
Christine
C
Dayer
Pierre
P
Sarasin
Alain
A
Hirvonen
Ari
A
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000209:etiology*; D010610:Pharyngeal Neoplasms / Q000209:etiology*; D011110:Polymorphism, Genetic; D017382:Reactive Oxygen Species; D012907:Smoking / Q000009:adverse effects*
D004268:DNA-Binding Proteins; D017382:Reactive Oxygen Species; C110901:X-ray repair cross complementing protein 3; C113187:XRCC2 protein, human