Abbasi Rashda, Ramroth Heribert, Becher Heiko, Dietz Andreas, Schmezer Peter, Popanda Odilia
Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center, Heidelberg, Germany.
Int J Cancer. 2009 Sep 15;125(6):1431-9. doi: 10.1002/ijc.24442.
Laryngeal cancer is known to be associated with smoking and high alcohol consumption. Nucleotide excision repair (NER) plays a key role in repairing DNA damage induced by these exposures and might affect laryngeal cancer susceptibility. In a population-based case-control study including 248 cases and 647 controls, the association of laryngeal cancer with 14 single nucleotide polymorphisms (SNPs) in 8 NER genes (XPC, XPA, ERCC1, ERCC2, ERCC4, ERCC5, ERCC6 and RAD23B) was analyzed with respect to smoking and alcohol exposure. For genotyping, sequence specific hybridization probes were used. Data were evaluated by conditional logistic regression analysis, stratified for age and gender, and adjusted for smoking, alcohol consumption and education. Pro-carriers of ERCC6 Arg1230Pro showed a decreased risk for laryngeal cancer (OR = 0.53, 95% CI 0.34-0.85), strongest in heavy smokers and high alcohol consumers. ERCC5 Asp1104His was associated with risk in heavy smokers (OR = 1.70, 95% CI 1.1-2.5). Val-carriers of RAD23B Ala249Val had an increased cancer risk in heavy smokers (OR = 1.6, 95% CI 1.1-2.5) and high alcohol consumers (OR = 2.0, 95% CI 1.1-3.4). The combined effect of smoking and alcohol intake affected risk, at high exposure level, for ERCC6 1230Pro carriers (OR = 0.47, 95% CI 0.22-0.98) and RAD23B 249Val carriers (OR = 2.6, 95% CI 1.3-4.9). When tested for gene-gene interaction, presence of 3 risk alleles in the XPC-RAD23B complex increased the risk 2.1-fold. SNPs in the other genes did not show a significant association with laryngeal cancer risk. We conclude that common genetic variations in NER genes can significantly modify laryngeal cancer risk.
已知喉癌与吸烟和大量饮酒有关。核苷酸切除修复（NER）在修复由这些暴露诱导的DNA损伤中起关键作用，并且可能影响喉癌易感性。在一项基于人群的病例对照研究中，该研究包括248例病例和647例对照，分析了喉癌与8个NER基因（XPC、XPA、ERCC1、ERCC2、ERCC4、ERCC5、ERCC6和RAD23B）中的14个单核苷酸多态性（SNP）与吸烟和酒精暴露的相关性。对于基因分型，使用了序列特异性杂交探针。数据通过条件逻辑回归分析进行评估，按年龄和性别分层，并对吸烟、饮酒和教育进行调整。ERCC6 Arg1230Pro的前体携带者患喉癌的风险降低（OR = 0.53，95% CI 0.34 - 0.85），在重度吸烟者和大量饮酒者中最为明显。ERCC5 Asp1104His与重度吸烟者的风险相关（OR = 1.70，95% CI 1.1 - 2.5）。RAD23B Ala249Val的缬氨酸携带者在重度吸烟者（OR = 1.6，95% CI 1.1 - 2.5）和大量饮酒者（OR = 2.0，95% CI 1.1 - 3.4）中患癌风险增加。吸烟和饮酒摄入的联合作用影响了ERCC6 1230Pro携带者（OR = 0.47，95% CI 0.22 - 0.98）和RAD23B 249Val携带者（OR = 2.6，95% CI 1.3 - 4.9）在高暴露水平下的风险。当测试基因 -基因相互作用时，XPC - RAD23B复合物中3个风险等位基因的存在使风险增加2.1倍。其他基因中的SNP与喉癌风险没有显著关联。我们得出结论，NER基因中的常见遗传变异可显著改变喉癌风险。
