Canova Cristina, Richiardi Lorenzo, Merletti Franco, Pentenero Monica, Gervasio Carmine, Tanturri Gabriella, Garzino-Demo Paolo, Pecorari Giancarlo, Talamini Renato, Barzan Luigi, Sulfaro Sandro, Franchini Giovanni, Muzzolini Chiara, Bordin Sandro, Pugliese Gaetano Natale, Macrì Ettore, Simonato Lorenzo
Department of Environmental Medicine and Public Health, University of Padua, Italy.
Tumori. 2010 Jan-Feb;96(1):1-10. doi: 10.1177/030089161009600101.
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.
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.
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.
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.
在意大利，每年约有14000例上消化道癌症新发病例，7000人死于该疾病，上消化道癌症包括起源于口腔、咽、喉和食管的恶性肿瘤。既定的病因包括吸烟和大量饮酒。对上消化道癌症病因中单个核苷酸多态性的研究可能有助于识别高危亚组，并更好地理解导致这些癌症发生的途径。
本文展示了在10个欧洲国家开展的一项大型病例对照研究（ARCAGE）中，意大利约500例病例和500例对照的研究结果，主要目的是更新意大利北部酒精和烟草消费影响的研究结果，调查基因变异在酒精和烟草烟雾致癌物代谢方面的作用，并评估这些单核苷酸多态性与这些致癌物之间可能的相互作用。
本研究证实了吸烟和饮酒作为上消化道癌症主要危险因素的重要性，表明意大利北部人群中约68%的癌症可归因于这些危险因素的综合作用。发现代谢I期基因（CYP1A1和CYP2A6）、II期基因（GSTA2）与上消化道癌症之间存在显著关联。ADH1C的一种多态性与上消化道癌症风险增加相关，这表明酒精代谢较慢的人群对上消化道癌症风险更易感。
我们的结果表明，ADH1C等位基因改变了上消化道中酒精的致癌剂量反应，从而产生了基因-环境相互作用。基因作为生活方式风险可能的调节因子的作用似乎最为可靠。
