肿瘤坏死因子基因多态性与结直肠癌易感性的相关性

Association of TNF gene polymorphisms with colorectal cancer risk

目的探讨肿瘤坏死因子(tumor necrosis factor,TNF)基因单核苷酸多态(single nucleotide polymorphisms,SNP)(TNF-αG-308A、TNF-αG-238A和TNF-βC804A)与结直肠癌(colorectal cancer,CRC)遗传易感性的关系。方法采用TaqMan方法,检测345例CRC患者与670例对照各SNP的基因型分布及差异。单体型分析采用Phase(2.1版)软件进行。结果TNF-α基因G-308A和G-238A基因型及等位基因分布在CRC、对照两组人群间差异均无统计学意义(P>0.05)。TNF-βC804A在两组人群中的等位基因分布差异有统计学意义(P=0.019)。与CC基因型相比,CA、AA基因型的CRC发病风险分别增加至1.29倍(95%CI=0.95～1.76,P= 0.107)和1.55倍(95%CI=1.07～2.25,P=0.021)。单体型分析结果显示,TNF单体型分布在CRC组和对照组间存在显著性差异(P=0.037)。与C^(804)G^(-308)G^(-238)单体型相比,A^(804)G^(-308)G^(-238)单体型增加CRC的发病风险(OR=1.20,95%CI=0.99～1.46,P=0.069)。结论TNF-α基因G-308A和G-238A多态与CRC发病风险无关;而携带TNF-β804A等位基因可增加CRC的发病风险。

Objective To study the possible association between the single nucleotide polymorphisms （SNP） （TNF-α G-308A,TNF-α G-238A and TNF-β C804A） in tumor necrosis factor （TNF） gene and susceptibility to colorectal cancer （CRC） in a Chinese population. Methods The genotypes of each SNP in TNF gene were determined by TaqMan assays in 345 CRC cases and 670 controls. Haplotype analysis was performed by using the Phase （2. 1 ） software. Results No significant association of G-308A or G-238A polymorphism in TNF-α gene with CRC risk was observed （ P 〉 0. 05 ）. The allele of TNF-β C804A polymorphism was significantly associated with CRC （P = 0. 019）. Compared to CC genotype, CA genotype had a 1.29-fold increased risk （95% CI = 0.95 -1.76, P = 0. 107）, whereas AA genotype had a significant 1.55-fold increased risk （95% CI = 1.07 -2.25, P = 0. 021 ） of CRC. The haplotype distribution of TNF gene in CRC cases was significantly different from that in the controls （ P = 0.037 ）. Compared with the most common C^804G^-308G^-238 haplotype, A^804G^-308G^-238 haplotype had an increased CRC risk （ OR = 1.20, 95 % CI = 0.99 -1.46, P = 0. 069 ）. Conclusion TNF-α G-308A and G-238A polymorphisms may be not associated with CRC risk. The allele of TNF-β C804A polymorphism may contribute to the etiology of CRC in the Chinese population.