Yang Xi, Zhang Chi, Zhu Hong-Cheng, Qin Qin, Zhao Lian-Jun, Liu Jia, Xu Li-Ping, Zhang Qu, Cai Jing, Ma Jian-Xin, Cheng Hong-Yan, Sun Xin-Chen
Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing, 210029, China.
Tumour Biol. 2014 Mar;35(3):2825-30. doi: 10.1007/s13277-013-1375-x. Epub 2013 Nov 30.
Hypoxia-inducible factor-1 (HIF-1) influences cancer progression and metastasis through various mechanisms, and HIF-1α polymorphisms are reportedly associated with many cancers; however, the associations of HIF-1α P582S and A588T polymorphisms with the risk of digestive system cancer remain inconclusive. To understand the role of HIF-1α P582S and A588T genotypes in digestive cancer development, we conducted a comprehensive meta-analysis involving 1,517 cases and 3,740 controls. Overall, the P582S polymorphism was not significantly associated with digestive system cancers in all genotypes. By contrast, the A588T polymorphism was significantly associated with digestive system cancers in the dominant model (TT/AT vs. AA: OR = 3.17, 95% CI: 1.21, 8.25; P heterogeneity < 0.001). In subgroup analysis for cancer types, the two polymorphisms were only associated with increased risk of pancreatic cancer (P582S: SS vs. PP: OR = 2.51, 95% CI: 1.31, 4.81; SS vs.
PP/PS: OR = 8.73, 95% CI: 1.33, 57.1; A588T: TT vs. AA: OR = 9.30, 95% CI: 1.12, 77.6; P heterogeneity = 0.478; TT vs.
AA/AT: OR = 3.14, 95% CI: 1.99, 4.97; P heterogeneity = 0.098; TT/AT vs. AA: OR = 8.65, 95% CI: 1.05, 71.6; P heterogeneity = 0.418). According to the source of ethnicity, the P582S and the A588T polymorphisms are both significantly associated with an increased risk of cancer among Caucasians in the homozygote model (SS vs. PP: OR = 2.41, 95% CI: 1.24, 4.691; P heterogeneity = 0.010; TT vs. AA: OR = 98.6, 95% CI: 4.37, 2,224; P heterogeneity = 0.040) and the recessive model (SS vs.
PP/PS: OR = 9.48, 95% CI: 1.12, 80.3; P heterogeneity < 0.001; TT vs.
AA/AT: OR = 82.7, 95% CI: 3.79, 1,802; P heterogeneity = 0.041). Our findings suggest that the HIF-1α A588T polymorphism is significantly associated with higher cancer risk and the P582S polymorphism is significantly associated with pancreatic cancer risk. Furthermore, the effect of both polymorphisms on digestive system cancer is more pronounced among Caucasians than that among Asians.
缺氧诱导因子-1（HIF-1）通过多种机制影响癌症进展和转移，据报道HIF-1α基因多态性与多种癌症相关；然而，HIF-1α P582S和A588T基因多态性与消化系统癌症风险的关联仍无定论。为了解HIF-1α P582S和A588T基因型在消化系统癌症发生中的作用，我们进行了一项综合荟萃分析，纳入1517例病例和3740例对照。总体而言，P582S基因多态性在所有基因型中与消化系统癌症均无显著关联。相比之下，A588T基因多态性在显性模型中与消化系统癌症显著相关（TT/AT与AA相比：OR = 3.17，95% CI：1.21，8.25；P异质性<0.001）。在癌症类型的亚组分析中，这两种基因多态性仅与胰腺癌风险增加相关（P582S：SS与PP相比：OR = 2.51，95% CI：1.31，4.81；SS与PP/PS相比：OR = 8.73，95% CI：1.33，57.1；A588T：TT与AA相比：OR = 9.30，95% CI：1.12，77.6；P异质性 = 0.478；TT与AA/AT相比：OR = 3.14，95% CI：1.99，4.97；P异质性 = 0.098；TT/AT与AA相比：OR = 8.65，95% CI：1.05，71.6；P异质性 = 0.418）。根据种族来源，P582S和A588T基因多态性在纯合子模型（SS与PP相比：OR = 2.41，95% CI：1.24，4.691；P异质性 = 0.010；TT与AA相比：OR = 98.6，95% CI：4.37，2224；P异质性 = 0.040）和隐性模型（SS与PP/PS相比：OR = 9.48，95% CI：1.12，80.3；P异质性<0.001；TT与AA/AT相比：OR = 82.7，95% CI：3.79，1802；P异质性 = 0.041）中均与高加索人患癌风险增加显著相关。我们的研究结果表明，HIF-1α A588T基因多态性与较高的癌症风险显著相关，P582S基因多态性与胰腺癌风险显著相关。此外，这两种基因多态性对消化系统癌症的影响在高加索人中比在亚洲人中更明显。
