title: The association of sequence variants in DNA repair and cell cycle genes with cancers of the upper aerodigestive tract.
abstract: 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.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Janet
authors.initials: J
authors.lastname: Hall
authors.forename: Mia
authors.initials: M
authors.lastname: Hashibe
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.forename: Valerie
authors.initials: V
authors.lastname: Gaborieau
authors.forename: Norman
authors.initials: N
authors.lastname: Moullan
authors.forename: Amelie
authors.initials: A
authors.lastname: Chabrier
authors.forename: David
authors.initials: D
authors.lastname: Zaridze
authors.forename: Oxana
authors.initials: O
authors.lastname: Shangina
authors.forename: Neonila
authors.initials: N
authors.lastname: Szeszenia-Dabrowska
authors.forename: Dana
authors.initials: D
authors.lastname: Mates
authors.forename: Vladimir
authors.initials: V
authors.lastname: Janout
authors.forename: Eleonóra
authors.initials: E
authors.lastname: Fabiánová
authors.forename: Ivana
authors.initials: I
authors.lastname: Holcatova
authors.forename: Rayjean J
authors.initials: RJ
authors.lastname: Hung
authors.forename: James
authors.initials: J
authors.lastname: McKay
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics; D005060:Europe; D005260:Female; D014644:Genetic Variation; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics; D010610:Pharyngeal Neoplasms / Q000235:genetics; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects