TNF-α308位点的基因多态性与环境因素对新疆哈萨克族食管癌家族发病的交互作用分析

Interaction between TNF-α 308 Polymorphisms and Environmental Factors in Xinjiang Kazakh Esophageal Cancer Families

目的：探讨肿瘤坏死因子-α（tumor necrosis factor alpha,TNF-α）的基因多态性及环境因素在新疆哈萨克族食管癌家族聚集中的交互作用。方法：在新疆北部食管癌高发区选取43例新疆哈萨克族食管癌家族成员及40例对照家族成员为研究对象,采用PCR-RFLP方法检测两组研究对象的外周血TNF-α308位点的基因型,对研究对象进行环境因素调查。结果：在新疆哈萨克族食管癌家族和非食管癌家族成员中TNF-α308位点的不同基因型分布差异有统计学意义（P=0.004,OR=8.786,95%CI：1.824～12.748）,在食管癌家族成员中TNF-α308位点基因携带突变基因AA型和GA型频率明显增高,是非食管癌家族成员的8.786倍;在食管癌患者与非患者之间TNF-α308位点的GG、GA、AA基因型分布差异有统计学意义（P=0.031,OR=2.821,95%CI为1.722～11.016）,与GG型相比,突变型基因可显著增加新疆哈萨克族食管癌的发病风险。分析TNF-α308位点的不同基因型与环境因素的交互作用,提示TNF-α308位点的基因多态性与饮酒（P=0.016,OR=1.531,95%CI：0.143～1.897）、暴饮暴食（P=0.021,OR=1.340,95%CI：0.266～3.789）在新疆哈萨克族食管癌家族发病可能起到交互作用。结论：TNF-α308位点基因多态性在新疆哈萨克族食管癌家族聚集中起一定作用。TNF-α308位点的基因多态性与饮酒、暴饮暴食在新疆哈萨克族食管癌家族发病中起到共同作用,可能与新疆哈萨克族食管癌高发有关。

Objective： To investigate the interaction of polymorphisms of TNF-α and environmental factors in pathogenesis of esophageal cancer families in Kazak in Xinjiang Province. Methods： In the northern part of Xinjiang,blood samples of 43 family members from esophageal cancer families in Kazak and 40 members from control families were collected. Genotype of TNF-α308 were determined by PCR-RFLP technology. Environmental factors were inquired by questionnaire. Results： There was significant statistic difference between Kazakh esophageal family and control family in the distribution frequency of the different gene type of TNF-α308（ P = 0. 004,OR = 8. 786,95% CI： 1. 824 ～ 12. 748）. The genotype frequencies of AA and GA of TNF-α308 were 8. 786 times higher in the Xinjiang Kazakh esophageal families than those of the control families with significant difference. Genotypes frequencies of GG、GA and AA at TNF-α308 were significantly different（ P = 0. 031,OR = 2. 821,95% CI： 1. 722 ～ 11. 016） between esophageal cancer patients and non-esophageal cancer patients. Mutant gene significantly increased the risk of developing esophageal cancer comparing with GG genotype. Analysis of interaction between the polymorphism of TNF-α308 and environmental factors revealed that alcohol,overeating and TNF-α 308 gene polymorphism had a multiplicative interaction in Kazakh esophageal cancer families. Conclusion： The polymorphism of TNF-α308 gene plays a role in the family aggregation of esophageal cancer in Xinjiang Kazakh. Alcohol,overeating and the polymorphism genotype of TNF-α308are likely to play a multiplicative interaction in esophageal families and may be related to the high incidence of esophageal cancer in Xinjiang Kazakh.