Xu Hong-Li, Hsing Ann W, Koshiol Jill, Chu Lisa W, Cheng Jia-Rong, Gao Jing, Tan Yu-Ting, Wang Bing-Sheng, Shen Ming-Chang, Gao Yu-Tang
Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200032, China.
Cancer Prevention Institute of California, Fremont, CA 94538, USA ; Stanford Cancer Institute, Palo Alto, CA 94305, USA.
Meta Gene. 2014 Dec 1;2:418-426. doi: 10.1016/j.mgene.2014.04.012.
Altered motility of the gallbladder can result in gallstone and cholecystitis, which are important risk factor for biliary tract cancer. Motilin (MLN) and somatostatin (SST) are known important modulators of gallbladder motility. To determine whether genetic variants in motilin, somatostatin, and their receptor genes are associated with the risk of biliary tract cancers and stones, nine tag-SNPs were determined in 439 biliary tract cancer cases (253 gallbladder, 133 extrahepatic bile duct and 53 ampulla of Vater cancer cases), 429 biliary stone cases, and 447 population controls in a population-based case-control study in Shanghai, China. We found that subjects with the rs9568169 AA genotype and rs169068 CC genotype were significantly associated with risk of extrahepatic bile duct cancer (OR =0.49, 95% CI: 0.27-0.89; OR =2.40, 95% CI: 1.13-5.13) compared to the major genotypes. rs2281820 CT and rs3793079 AT genotypes had significantly increased risks of gallstones (OR =1.52, 95% CI: 1.06-2.18; OR =1.64, 95% CI: 1.20-2.25) compared to TT genotypes. Besides, Haplotype analysis showed that T-T-T haplotype (rs2281820-rs3793079-rs2281819) had a non-significantly elevated risk of gallstone (OR =1.30, 95% CI: 0.91-1.86) compared with C-A-A haplotype. To the best of our knowledge, this is the first study to report an association between genetic polymorphisms in , and their receptor genes and risk of biliary tract cancers and stones.
胆囊运动功能改变可导致胆结石和胆囊炎,而这是胆管癌的重要危险因素。胃动素(MLN)和生长抑素(SST)是已知的胆囊运动重要调节因子。为了确定胃动素、生长抑素及其受体基因的遗传变异是否与胆管癌和结石的风险相关,在中国上海进行的一项基于人群的病例对照研究中,对439例胆管癌病例(253例胆囊癌、133例肝外胆管癌和53例 Vater壶腹癌病例)、429例胆结石病例和447名人群对照确定了9个标签单核苷酸多态性(tag-SNP)。我们发现,与主要基因型相比,携带rs9568169 AA基因型和rs169068 CC基因型的受试者与肝外胆管癌风险显著相关(比值比[OR]=0.49,95%可信区间[CI]:0.27-0.89;OR=2.40,95%CI:1.13-5.13)。与TT基因型相比,rs2281820 CT和rs3793079 AT基因型的胆结石风险显著增加(OR=1.52,95%CI:1.06-2.18;OR=1.64,95%CI:1.20-2.25)。此外,单倍型分析显示,与C-A-A单倍型相比,T-T-T单倍型(rs2281820-rs3793079-rs2281819)的胆结石风险有非显著升高(OR=1.30,95%CI:0.91-1.86)。据我们所知,这是第一项报告胃动素、生长抑素及其受体基因的遗传多态性与胆管癌和结石风险之间关联的研究。