Bau Da-Tian, Tsai Ming-Hsui, Huang Chih-Yang, Lee Cheng-Chun, Tseng Hsien-Chang, Lo Yen-Li, Tsai Yuhsin, Tsai Fuu-Jen
Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, ROC.
Chin J Physiol. 2007 Dec 31;50(6):294-300.
Inherited polymorphisms in DNA repair genes may be associated with differences in the repair capacity and contribute to individual's susceptibility to smoking-related cancers. Both XPA and XPD encode proteins that are part of the nucleotide excision repair (NER) pathway. In a hospital-based case-control study, we have investigated the influence of XPA A-23G and XPD Lys751Gln polymorphisms on oral cancer risk in a Taiwanese population. In total, 154 patients with oral cancer, and 105 age-matched controls recruited from the Chinese Medical Hospital in Central Taiwan were genotyped. No significant association was found between the heterozygous variant allele (AG), the homozygous variant allele (AA) at XPA A-23G, the heterozygous variant allele (AC), the homozygous variant allele (CC) at XPD Lys751Gln, and oral cancer risk. There was no significant joint effect of XPA A-23G and XPD Lys751Gln on oral cancer risk either. Since XPA and XPD are both NER genes, which are very important in removing tobacco-induced DNA adducts, further stratified analyses of both genotype and smoking habit were performed. We found a synergistic effect of variant genotypes of both XPA and XPD, and smoking status on oral cancer risk. Our results suggest that the genetic polymorphisms are modified by environmental carcinogen exposure status, and combined analyses of both genotype and personal habit record are a better access to know the development of oral cancer and useful for primary prevention and early intervention.
DNA修复基因中的遗传多态性可能与修复能力的差异有关，并导致个体对吸烟相关癌症的易感性。XPA和XPD都编码作为核苷酸切除修复（NER）途径一部分的蛋白质。在一项基于医院的病例对照研究中，我们调查了XPA A-23G和XPD Lys751Gln多态性对台湾人群口腔癌风险的影响。总共对154例口腔癌患者和从台湾中部中国医药大学招募的105名年龄匹配的对照进行了基因分型。在XPA A-23G的杂合变异等位基因（AG）、纯合变异等位基因（AA）、XPD Lys751Gln的杂合变异等位基因（AC）、纯合变异等位基因（CC）与口腔癌风险之间未发现显著关联。XPA A-23G和XPD Lys751Gln对口腔癌风险也没有显著的联合作用。由于XPA和XPD都是NER基因，在去除烟草诱导的DNA加合物方面非常重要，因此对基因型和吸烟习惯进行了进一步的分层分析。我们发现XPA和XPD的变异基因型与吸烟状况对口腔癌风险有协同作用。我们的结果表明，基因多态性受环境致癌物暴露状况的影响，基因型和个人习惯记录的综合分析是了解口腔癌发展的更好途径，对一级预防和早期干预有用。
