Carcinogenesis Advance Access originally published online on October 13, 2006
Carcinogenesis 2007 28(3):665-671; doi:10.1093/carcin/bgl160
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The association of sequence variants in DNA repair and cell cycle genes with cancers of the upper aerodigestive tract
1 International Agency for Research on Cancer Lyon, France
2 Cancer Research Centre Moscow, Russia
3 Institute of Occupational Medicine Lodz, Poland
4 Institute of Hygiene, Public Health, Health Services and Management Bucharest, Romania
5 Faculty of Medicine, Palacky University Olomouc, Czech Republic
6 Specialized State Health Institute, Banská Bystrica Slovakia
7 Institute of Hygiene and Epidemiology, Prague, Czech Republic CA, USA
8 School of Public Health, University of California at Berkeley CA, USA
9 German Cancer Research Center (DKFZ), Heidelberg Germany
10 Institut Curie, Centre de Recherche, Orsay France
*To whom correspondence should be addressed at: Genetic Epidemiology Group, International Agency for Research on Cancer, 150, cours Albert Thomas, 69372 Lyon, France. Tel: +33 4 72 73 8391; Fax: +33 4 72 73 84 32; Email: brennan{at}iarc.fr
Cancers of the upper aerodigestive tract (UADT), comprising the oral cavity, pharynx, larynx and oesophagus, account for 5.2% of all cancers cases worldwide. The major risk factors, tobacco and alcohol can directly or indirectly generate DNA damage, which if unrepaired can give rise to mutations, unregulated cell growth and apoptosis induction. To clarify the role of DNA repair and cell cycle control proteins in UADT cancer susceptibility, we studied the risk in relation to 28 SNPs in 18 DNA repair enzymes and 9 SNPs in 7 cell cycle control genes. A case-control study was conducted from 2000 to 2002 in six centers from Romania, Poland, Russia, Slovakia and the Czech Republic. Patients diagnosed with squamous cell carcinoma of the UADT (n = 811) and controls with a recent diagnosis of diseases unrelated to tobacco and alcohol (n = 1083) were recruited. For UADT cancer risk, associations were observed for the homozygous carriers of the variant alleles of MGMT L84F [odds ratio (OR) 2.35, 95% confidence interval (CI) 1.32–4.20], MGMT 171C > T (OR 2.24, 95% CI 1.20–4.17) and OGG1 S326C (OR 2.07, 95% CI 1.15–3.73) whilst three variants were associated with a protective effect (XPA 23G > A, P for trend 0.022, APEX Q51H, P for trend 0.036, CHEK2 intron 9-200T > C, P for trend 0.009). Several other sequence variants showed associations with specific cancers without an overall association with UADT cancer. While some of these associations are consistent with previous studies, we cannot rule out the possibility of false-positive associations. The positive findings should be explored in another large-scale study on UADT cancers.
Abbreviations: UADT, upper aerodigestive tract; BER, base excision repair; FPRP, false-positive report probability; OR, odds ratio; CI, confidence interval
Received May 22, 2006; revised August 3, 2006; accepted August 25, 2006.
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