Du Li Chuan, Gao Ru
Department of Gastroenterology, Beijing Chaoyang Hospital, Beijing, China.
Turk J Gastroenterol. 2017 Jul;28(4):272-282. doi: 10.5152/tjg.2017.16741.
BACKGROUND/AIMS: In the Chinese population, gastric cancer (GC) is ranked as the third most common type of cancer. Although the exact etiology of GC development is unclear, several factors, including genetic and environmental, have been identified as risk factors. Variations in cytokine genes and their receptors have been related to a higher risk of GC. A single nucleotide polymorphism in the promoter region of tumor necrosis factor-α (TNF-α) (-308G>A) has been associated with a higher risk of GC and in the present study we evaluated its possible association with GC in a Chinese cohort. In addition, we performed a meta-analysis to draw a firm conclusion about the association between TNF-α gene polymorphisms and GC.
We enrolled 400 Chinese GC patients and matched healthy controls hailing from similar geographical areas. The TNF-α -308G/A polymorphism was genotyped by allele-specific polymerase chain reaction (AS-PCR). For the meta-analysis, earlier published articles were searched and eligible studies were included.
Prevalence of the heterozygous mutant (GA) and minor allele (A) were significantly higher in GC cases compared to healthy controls (GA: p<0.0001, odds ratio (OR)=4.90; A: p<0.0001, OR=2.84). A total of 36 eligible studies including the present report, encompassing of 8353 GC patients and 12099 controls, were analyzed for the meta-analysis. A significant association of the TNF-α polymorphism (-308G>A) with susceptibility to GC was only found in the Caucasian population (A vs G: p=0.001; AA vs GG: p=0.01; AG vs GG: p<0.0001; AA vs AG+GG: p=0.01; AA+AG vs p=0.003).
The results of the present case control study and meta-analysis showed that associations between TNF-a variants with susceptibility to GC development is population and ethnic specific.
背景/目的：在中国人群中，胃癌（GC）是第三大常见癌症类型。尽管胃癌发生的确切病因尚不清楚，但已确定包括遗传和环境因素在内的多种因素为危险因素。细胞因子基因及其受体的变异与胃癌风险升高有关。肿瘤坏死因子-α（TNF-α）启动子区域的单核苷酸多态性（-308G>A）与胃癌风险升高相关，在本研究中，我们评估了其在中国队列中与胃癌的可能关联。此外，我们进行了一项荟萃分析，以就TNF-α基因多态性与胃癌之间的关联得出确凿结论。
我们招募了400名中国胃癌患者以及来自相似地理区域的匹配健康对照。通过等位基因特异性聚合酶链反应（AS-PCR）对TNF-α -308G/A多态性进行基因分型。对于荟萃分析，检索了早期发表的文章并纳入符合条件的研究。
与健康对照相比，胃癌病例中杂合突变体（GA）和次要等位基因（A）的患病率显著更高（GA：p<0.0001，优势比（OR）=4.90；A：p<0.0001，OR=2.84）。对包括本报告在内的总共36项符合条件的研究进行了荟萃分析，这些研究涵盖8353名胃癌患者和12099名对照。仅在白种人群中发现TNF-α多态性（-308G>A）与胃癌易感性存在显著关联（A与G相比：p=0.001；AA与GG相比：p=0.01；AG与GG相比：p<0.0001；AA与AG+GG相比：p=0.01；AA+AG与GG相比：p=0.003）。
本病例对照研究和荟萃分析的结果表明，TNF-α变体与胃癌发生易感性之间的关联具有人群和种族特异性。
