Variation in TCF7L2 and increased risk of colon cancer -: The Atherosclerosis Risk in Communities (ARIC) Study
Variation in TCF7L2 and increased risk of colon cancer -: The Atherosclerosis Risk in Communities (ARIC) Study
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DOI：
10.2337/dc07-2131
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发表时间：
2008-05-01
期刊：
影响因子：
16.2
通讯作者：
Boerwinkle, Eric
中科院分区：
文献类型：
--
作者：
Folsom, Aaron R.;Pankow, James S.;Boerwinkle, Eric
目的-这项研究的目的是确定是否在转录因子7样2（TCF 7 L2）基因的变化，影响糖尿病的风险，与cancers.Research设计和方法的发病率-我们相关的糖尿病和TCF 7 L2变异与几种常见癌症的发生在一个前瞻性队列研究13，1987-1989年，117名中年人最初没有癌症。我们评估了TCF 7 L2的5个单核苷酸多态性（SNP），包括糖尿病的推定SNP（rs7903146）。我们通过2000年的癌症登记，补充医院records.RESULTS -糖尿病与前列腺癌的发病率呈轻微负相关，但与结直肠癌、结肠癌、肺癌或乳腺癌的发病率无关。rs7903146的T等位基因（频率30%）与结直肠癌的风险增加相关，更具体地说，结肠癌，CC的校正风险比（95%CI）为1.0，CT为1.25（0.85-1.83），TT基因型为2.15（1.27-3.64）（P趋势= 0.009）。TCF 7 L2变异也与肺癌的发病率在白人，但不是黑人，但残留的混杂吸烟可能present.CONCLUSIONS -受试者最初是无癌和携带某些遗传变异的TCF 7 L2，最显着的T等位基因rs79031.46，结肠癌的风险增加。这种关联似乎是一种独立的基因效应，不能用糖尿病来解释。由于rs7903146的T等位基因很常见，如果建立了因果关系，这种变异可能会在普通人群中占相当大的比例（类似于17%）。
OBJECTIVE - The purpose of this study was to determine whether a variation in the transcription factor 7-like 2 (TCF7L2) gene, which influences diabetes risk, is associated with incidence of cancers.RESEARCH DESIGN AND METHODS - We related diabetes and TCF7L2 variation with occurrence of several common cancers in a prospective cohort study of 13,117 middle-aged adults initially free of cancer in 1987-1989. We assessed five single nucleotide polymorphisms (SNPs) in TCF7L2 including the putative SNP (rs7903146) for diabetes. We identified incident cancers through 2000 via cancer registries, supplemented by hospital records.RESULTS - Diabetes was associated marginally inversely with incidence of prostate cancer but not with incidence of colorectal, colon, lung, or breast cancer. The T allele of rs7903146 (frequency 30%) was associated with increased risk of colorectal cancer and, more specifically, colon cancer, with adjusted hazard ratios (95% CI) of 1.0 for CC, 1.25 (0.85-1.83) for CT, and 2.15 (1.27-3.64) for TT genotypes (P-trend = 0.009). TCF7L2 variation also was associated with lung cancer incidence in whites but not blacks, but residual confounding by smoking may be present.CONCLUSIONS - Subjects who were initially cancer-free and carrying certain genetic variants of TCF7L2, most notably the T allele of rs79031.46, have an increased risk of colon cancer. This association appears to be an independent gene effect not explained by diabetes. Because the T allele of rs7903146 is common, if a causal link is established, this variant could account for a sizable proportion (similar to 17% here) of cases of colon cancer in the general population.