title: Alcohol, tobacco and genetic susceptibility in relation to cancers of the upper aerodigestive tract in northern Italy.
abstract: OBJECTIVE
  Each year in Italy there are approximately 14,000 new cases and 7,000 deaths from cancer of the upper aerodigestive tract, which includes malignant tumors originating from the oral cavity, pharynx, larynx and esophagus. Established etiological factors include tobacco consumption and heavy alcohol drinking. The study of single nucleotide polymorphisms in upper aerodigestive tract cancer etiology may help to identify high-risk subgroups and to better understand the pathways leading to the development of these cancers.
  
  
  METHODS
  Italian results on about 500 cases and 500 controls from a large case-control study (ARCAGE) conducted in 10 European countries are presented with the major objectives of updating results on the effects of alcohol and tobacco consumptions in northern Italy, investigating the role of genetic variation with regard to the metabolism of alcohol and carcinogens from tobacco smoke, and evaluating possible interactions of these single nucleotide polymorphisms with these carcinogens.
  
  
  RESULTS
  The present study confirmed the importance of tobacco smoking and alcohol drinking as the main risk factors for upper aerodigestive tract cancers, indicating that about 68% of cancers among populations in northern Italy can be attributed to the combination of these risk factors. Significant associations between metabolizing phase I genes (CYP1A1 and CYP2A6), phase II genes (GSTA2) and upper aerodigestive tract cancers were found. A polymorphism of ADH1C has been associated with an increased risk of upper aerodigestive tract cancers, suggesting that the less rapid alcohol metabolizers are more susceptible to upper aerodigestive tract cancer risk.
  
  
  CONCLUSIONS
  Our results suggest that the ADH1C allele modifies the carcinogenic dose response for alcohol in the upper aerodigestive tract, giving rise to a gene-environment interaction. The role of genes as possible modifiers of life-style risks seems the most reliable.
authors.affiliation: Department of Environmental Medicine and Public Health, University of Padua, Italy. cristina.canova@unipd.it
authors.forename: Cristina
authors.initials: C
authors.lastname: Canova
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Richiardi
authors.forename: Franco
authors.initials: F
authors.lastname: Merletti
authors.forename: Monica
authors.initials: M
authors.lastname: Pentenero
authors.forename: Carmine
authors.initials: C
authors.lastname: Gervasio
authors.forename: Gabriella
authors.initials: G
authors.lastname: Tanturri
authors.forename: Paolo
authors.initials: P
authors.lastname: Garzino-Demo
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Pecorari
authors.forename: Renato
authors.initials: R
authors.lastname: Talamini
authors.forename: Luigi
authors.initials: L
authors.lastname: Barzan
authors.forename: Sandro
authors.initials: S
authors.lastname: Sulfaro
authors.forename: Giovanni
authors.initials: G
authors.lastname: Franchini
authors.forename: Chiara
authors.initials: C
authors.lastname: Muzzolini
authors.forename: Sandro
authors.initials: S
authors.lastname: Bordin
authors.forename: Gaetano Natale
authors.initials: GN
authors.lastname: Pugliese
authors.forename: Ettore
authors.initials: E
authors.lastname: Macrì
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Simonato
mesh_terms: D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000009:adverse effects*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D065637:Cytochrome P-450 CYP2A6; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000209:etiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000453:epidemiology* / Q000209:etiology* / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D007558:Italy / Q000453:epidemiology; D007822:Laryngeal Neoplasms / Q000453:epidemiology / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000453:epidemiology / Q000209:etiology; D016017:Odds Ratio; D010610:Pharyngeal Neoplasms / Q000453:epidemiology / Q000209:etiology; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects*
chemical_list: D007527:Isoenzymes; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D019363:Cytochrome P-450 CYP1A1; D065637:Cytochrome P-450 CYP2A6; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha