Singh Seram Anil, Choudhury Javed Hussain, Kapfo Wetetsho, Kundu Sharbadeb, Dhar Bishal, Laskar Shaheen, Das Raima, Kumar Manish, Ghosh Sankar Kumar
Molecular Medicine Laboratory, Department of Biotechnology, Assam University, Silchar, Assam, India E-mail :
Asian Pac J Cancer Prev. 2015;16(16):6953-61. doi: 10.7314/apjcp.2015.16.16.6953.
Tobacco and alcohol contain or may generate carcinogenic compounds related to cancers. CYP1A1 enzymes act upon these carcinogens before elimination from the body. The aim of this study was to investigate whether CYP1A1 T3801C polymorphism modulates the relationship between tobacco and alcohol- associated head and neck cancer (HNC) susceptibility among the northeast Indian population.
One hundred and seventy histologically confirmed HNC cases and 230 controls were included within the study. The CYP1A1 T3801C polymorphism was determined using PCR-RFLP, and the results were confirmed by DNA sequencing. Logistic regression (LR) and multifactor dimensionality reduction (MDR) approaches were applied for statistical analysis.
The CYP1A1 CC genotype was significantly associated with HNC risk (P=0.045). A significantly increased risk of HNC (OR=6.09; P<0.0001) was observed in individuals with combined habits of smoking, alcohol drinking and tobacco-betel quid chewing. Further, gene-environment interactions revealed enhanced risks of HNC among smokers, alcohol drinkers and tobacco-betel quid chewers carrying CYP1A1 TC or CC genotypes. The highest risk of HNC was observed among smokers (OR=7.55; P=0.009) and chewers (OR=10.8; P<0.0001) carrying the CYP1A1 CC genotype. In MDR analysis, the best model for HNC risk was the three-factor model combination of smoking, tobacco-betel quid chewing and the CYP1A1 variant genotype (CVC=99/100; TBA=0.605; P<0.0001); whereas interaction entropy graphs showed synergistic interaction between tobacco habits and CYP1A1.
Our results confirm that the CYP1A1 T3801C polymorphism modifies the risk of HNC and further demonstrated importance of gene-environment interaction.
烟草和酒精含有或可能产生与癌症相关的致癌化合物。CYP1A1酶在这些致癌物从体内消除之前对其起作用。本研究的目的是调查CYP1A1 T3801C多态性是否调节印度东北部人群中烟草和酒精相关的头颈癌（HNC）易感性之间的关系。
本研究纳入了170例经组织学确诊的HNC病例和230例对照。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）确定CYP1A1 T3801C多态性，并通过DNA测序确认结果。应用逻辑回归（LR）和多因素降维（MDR）方法进行统计分析。
CYP1A1 CC基因型与HNC风险显著相关（P=0.045）。在有吸烟、饮酒和嚼烟草-槟榔习惯的个体中，观察到HNC风险显著增加（优势比[OR]=6.09；P<0.0001）。此外，基因-环境相互作用显示，携带CYP1A1 TC或CC基因型的吸烟者、饮酒者和嚼烟草-槟榔者患HNC的风险增加。在携带CYP1A1 CC基因型的吸烟者（OR=7.55；P=0.009）和嚼槟榔者（OR=10.8；P<0.0001）中观察到最高的HNC风险。在MDR分析中，HNC风险的最佳模型是吸烟、嚼烟草-槟榔和CYP1A1变异基因型的三因素模型组合（交叉验证一致性[CVC]=99/100；训练平衡准确率[TBA]=0.605；P<0.0001）；而相互作用熵图显示烟草习惯与CYP1A1之间存在协同相互作用。
我们的结果证实，CYP1A1 T3801C多态性改变了HNC的风险，并进一步证明了基因-环境相互作用的重要性。
