Genetic variation in calcium-sensing receptor and risk for colon cancer.
Genetic variation in calcium-sensing receptor and risk for colon cancer.
复制标题
DOI：
10.1158/1055-9965.epi-08-0388
复制
发表时间：
2008-10
影响因子：
3.8
通讯作者：
Peters, Ulrike
中科院分区：
文献类型：
--
作者：
Dong, Linda M.;Ulrich, Cornelia M.;Hsu, Li;Duggan, David J.;Benitez, Debbie S.;White, Emily;Slattery, Martha L.;Caan, Bette J.;Potter, John D.;Peters, Ulrike
实验和流行病学研究表明，高钙摄入量与结肠癌风险降低有关。然而，关于钙/维生素D途径中的候选基因和结肠癌风险的数据非常有限。为了解决这个问题，我们评估了钙敏感受体（CASR）单核苷酸多态性（SNP）是否与结肠癌风险相关。我们还研究了CASR与钙和维生素D摄入量之间的相互作用，以及先前对维生素D相关基因进行的基因分型。我们对1,600例病例和1,949例对照进行了一项大型多中心基于人群的病例对照研究。基于重测序数据，从常见SNPs（次要等位基因频率≥5%）中选择17个CASR标签SNPs。使用HaploStats估计和评价单倍型。我们没有观察到任何CASR基因型或单倍型与结肠癌风险之间的关联。然而，当按解剖部位分层时，发现与近端结肠癌风险有统计学显著相关性（rs10934578 TT：OR 1.35，95%CI 1.01-1.81; rs12485716 AG/AA：OR 0.84，95%CI 0.71-1.00; rs4678174 CT/CC：OR 0.83，95%CI 0.70-0.98; rs2270916 CC：OR 0.43，95%CI 0.19-0.97）。一致地，我们观察到CASR单倍型（rs 4678174，rs 2270916）与近端结肠癌风险的相关性（总体p值=0.08）。我们没有观察到任何有意义的基因-环境（钙和维生素D）或基因-基因（CYP 24 A1，CYP 27 B1和VDR）相互作用与CASR基因型和结肠癌风险。我们的研究没有提供CASR SNP与结肠癌之间总体关联的证据;然而，结果表明CASR对近端结肠癌的可能作用和亚位点差异与已知的钙生物学一致。然而，这些调查结果需要确认。
Experimental and epidemiologic studies have suggested that high calcium intake is associated with decreased colon cancer risk. Yet very limited data are available for candidate genes in the calcium/vitamin D pathway and colon cancer risk. To address this, we evaluated whether calcium sensing receptor(CASR) single nucleotide polymorphisms(SNP) are associated with colon cancer risk. We also examined interactions between CASR and calcium and vitamin D intake, and previously genotyped vitamin D-related genes. We conducted a large multi-center population-based case-control study of 1,600 cases and 1,949 controls. Seventeen tagging SNPs for CASR were selected from common SNPs (minor allele frequency ≥5%) based on resequencing data. Haplotypes were estimated and evaluated using HaploStats. We did not observe an association between any CASR genotypes or haplotypes and colon cancer risk overall. However, when stratified by anatomic site, statistically significant associations were seen with risk of proximal colon cancer (rs10934578 TT: OR 1.35, 95%CI 1.01-1.81; rs12485716 AG/AA: OR 0.84, 95%CI 0.71-1.00; rs4678174 CT/CC: OR 0.83, 95%CI 0.70-0.98; rs2270916 CC: OR 0.43, 95%CI 0.19-0.97). Concordantly, we observed a suggested association for a CASR haplotype (rs4678174, rs2270916) with risk of proximal colon cancer (global p-value=0.08). We did not observe any meaningful gene-environment (calcium and vitamin D) or gene-gene (CYP24A1, CYP27B1, and VDR) interactions with CASR genotypes and colon cancer risk. Our study does not provide evidence for an overall association between CASR SNPs and colon cancer; however, results suggest a possible role of CASR on proximal colon cancer and subsite differences are consistent with known calcium biology. Nonetheless, these findings require confirmation.