Alcohol, tobacco and genetic susceptibility in relation to cancers of the upper aerodigestive tract in northern Italy.
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.
Canova
Cristina
C
Department of Environmental Medicine and Public Health, University of Padua, Italy. cristina.canova@unipd.it
Richiardi
Lorenzo
L
Merletti
Franco
F
Pentenero
Monica
M
Gervasio
Carmine
C
Tanturri
Gabriella
G
Garzino-Demo
Paolo
P
Pecorari
Giancarlo
G
Talamini
Renato
R
Barzan
Luigi
L
Sulfaro
Sandro
S
Franchini
Giovanni
G
Muzzolini
Chiara
C
Bordin
Sandro
S
Pugliese
Gaetano Natale
GN
Macrì
Ettore
E
Simonato
Lorenzo
L
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*
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