The Influence of Gene Polymorphisms on Tobacco and Alcohol-Induced Oral Cancer Risk

作     者：Otávio A.Curioni Marcos B.de Carvalho Rogerio A.Dedivitis Abrao Rapoport Gilka J.F.Gattas 

作者机构：Department of Head and Neck Surgery and Otorhinolaryngology of the Heliopolis HospitalSao PauloBrazil Department of Legal MedicineBioethics and Occupational HealthSchool of MedicineSao PauloBrazil Head and Neck Surgeon of Sao Jose HospitalSao PauloBrazil Department of Head and Neck SurgeryHospital das ClinicasSao Paulo School of MedicineUniversity of Sao PauloSao PauloBrazil 

出 版 物：《Journal of Cancer Therapy》 (癌症治疗（英文）)

年 卷 期：2013年第4卷第5期

页      面：978-988页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo(FAPESP)and LIM-HC-FMUSP 

主　　题：Mouth Neoplasms Head and Neck Neoplasms Polymorphism Genetic Smoking Alcohol Drinking 

摘      要：Aims: This study examined whether genetic polymorphisms of tobacco and alcohol-related metabolic genes such as GSTM1, GSTT1, GSTP1, CYP1A1, CYP2E1 and DNA repair genes (XRCC1 194Trp, XRCC1 399Gln, and XRCC3 Met) contribute to the risk of developing OSCC. Methods: Patients eligible for inclusion were over 18 years, had pathologically confirmed OSCC and were followed prospectively for at least two years or until death, from December 2000 to December 2004. Ninety-two OSCC patients were included along with 244 subjects from the same hospital, evaluated in the same period as patients without cancer, as the control group. Results: GSTM1 null and XRCC1-194Trp alone increased the risk of OSCC (OR, 2.15;95% CI, 1.2 - 3.6 and OR, 2.02;95% CI, 1.01 - 4.03, respectively). The joint effect of GSTM1 null with CYP1A1 or CYP2E1 polymorphism increased the risk two to threefold. Similar results were observed when XRCC1-194Trp was combined with GSTM1 null or the CYP2E1 polymorphism. By contrast, XRCC1- 399Gln was associated with protection against OSCC. Gene-gene and gene-environmental interactions were mainly detected for CYP1A1 and GSTP1 associated with more than 20 p/y of tobacco and XRCC1-194Trp when more than 30 g/L/d of alcohol was consumed (OR, 8.8;95% CI;1.3 - 45.7). Conclusions: The drug metabolizing and DNA repair enzyme polymorphisms may be informative for clinicians in the preventive management of patients at risk, particularly those with strong smoking and drinking habits.