Carcinogenesis Advance Access published online on October 13, 2006
Carcinogenesis, doi:10.1093/carcin/bgl160
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1 International Agency for Research on Cancer, Lyon, France; Institut Curie, Paris, France
* To whom correspondence should be addressed. Cancers of the upper aerodigestive tract (UADT), comprising the oral cavity, pharynx, larynx and esophagus, 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 6 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 (OR 2.35, 95% 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 23 G>A, P for trend 0.022, APEX Q51H, P for trend 0.036, CHEK2 intron9-200T>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.
Received May 22, 2006
Revised August 3, 2006
Accepted August 25, 2006
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
The association of sequence variants in DNA repair and cell cycle genes with cancers of the upper aerodigestive tract
Janet Hall 1, Mia Hashibe 2, Paolo Boffetta 2, Valerie Gaborieau 2, Norman Moullan 2, Amelie Chabrier 2, David Zaridze 3, Oxana Shangina 3, Neonila Szeszenia-Dabrowska 4, Dana Mates 5, Vladimir Janout 6, Eleonóra Fabiánová 7, Ivana Holcatova 8, Rayjean J. Hung 9, James McKay 2, Federico Canzian 10, and Paul Brennan 2 *
2 International Agency for Research on Cancer, Lyon, France
3 Cancer Research Centre, Moscow, Russia
4 Institute of Occupational Medicine, Lodz, Poland
5 Institute of Hygiene, Public Health, Health Services and Management, Bucharest, Romania
6 Faculty of Medicine, Palacky University, Olomouc, Czech Republic
7 Specialized State Health Institute, Banská Bystrica, Slovakia
8 Institute of Hygiene and Epidemiology, Prague, Czech Republic
9 International Agency for Research on Cancer, Lyon, France; School of Public Health, University of California at Berkeley, CA, USA
10 International Agency for Research on Cancer, Lyon, France; German Cancer Research Center (DKFZ), Heidelberg, Germany
Paul Brennan, E-mail: brennan{at}iarc.fr
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