National Institute of Public Health, Prague, Czech Republic.
Neoplasma. 2010;57(5):415-21. doi: 10.4149/neo_2010_05_415.
The question of susceptibility to squamous cell carcinoma of head and neck (SCCHN) in the environmental context was addressed by analysis of functional polymorphisms in enzymes metabolizing smoke constituents and/or alcohol (CYP2A13, CYP1B1, EPHX1, NQO1, GSTM1, GSTP1, GSTT1, ADH1B and ADH1C). Case-control study of 122 age- and sex-matched pairs of subjects was performed using so far unexplored Central European Slavic population with high level of tobacco and alcohol abuse. Age-, gender-, smoking- and alcohol-adjusted logistic regression failed to demonstrate any significant association of the analyzed polymorphisms with the SCCHN risk. When interactions between potential modifiers of effect, i.e. smoking and alcohol were tested, drinkers seemed to be at lower risk than nondrinkers when carrying the heterozygous genotype Ile/Val in codon 432 of CYP1B1 (OR=0.42; 95% CI=0.21-0.83; p=0.013 vs. OR=1.02; 95% CI=0.34-2.94; p=0.977). Similarly, drinkers were at lower risk than nondrinkers when carrying the heterozygous genotype Pro/Ser in codon 187 of NQO1 (OR=0.41; 95% CI=0.19-0.88; p=0.022 vs. OR=0.96; 95% CI=0.29-3.12; p=0.948). More interestingly, drinkers carrying the rare homozygous genotype Val/Val in codon 350 of ADH1C were at significantly higher risk than nondrinkers carrying this genotype (OR=4.01; 95% CI=1.61-10.01; p=0.003 vs. OR=0.93; 95% CI=0.25-3.57; p=0.919). This result confirmed findings of previously published studies. Smoking did not significantly modify the effect of genotypes. Our data thus demonstrate that genetic susceptibility to SCCHN shall be further followed on populations with different genetic background and lifestyle.
本研究分析了代谢烟雾成分和/或酒精的酶的功能多态性,探讨了环境背景下头颈部鳞状细胞癌(SCCHN)易感性的问题。采用迄今尚未在烟草和酒精滥用水平较高的中欧斯拉夫人群中探索过的病例对照研究,对 122 对年龄和性别匹配的研究对象进行了研究。在调整年龄、性别、吸烟和饮酒因素后,逻辑回归分析未能显示分析的多态性与 SCCHN 风险之间存在任何显著关联。当测试潜在效应修饰因子(即吸烟和饮酒)之间的相互作用时,携带 CYP1B1 密码子 432 处异亮氨酸/缬氨酸杂合基因型的饮酒者似乎比不饮酒者的风险更低(OR=0.42;95%CI=0.21-0.83;p=0.013 与 OR=1.02;95%CI=0.34-2.94;p=0.977)。同样,携带 NQO1 密码子 187 处脯氨酸/丝氨酸杂合基因型的饮酒者比不饮酒者的风险更低(OR=0.41;95%CI=0.19-0.88;p=0.022 与 OR=0.96;95%CI=0.29-3.12;p=0.948)。更有趣的是,携带 ADH1C 密码子 350 处罕见纯合基因型缬氨酸/缬氨酸的饮酒者比携带该基因型的不饮酒者的风险显著更高(OR=4.01;95%CI=1.61-10.01;p=0.003 与 OR=0.93;95%CI=0.25-3.57;p=0.919)。该结果证实了先前发表研究的发现。吸烟并未显著改变基因型的作用。因此,我们的数据表明,对具有不同遗传背景和生活方式的人群应进一步研究 SCCHN 的遗传易感性。