Common variant in 6q26-q27 is associated with distal colon cancer in an Asian population.
Common variant in 6q26-q27 is associated with distal colon cancer in an Asian population.
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DOI：
10.1136/gut.2010.215947
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发表时间：
2011-06
期刊：
影响因子：
24.5
通讯作者：
Matsuda K
中科院分区：
文献类型：
--
作者：
Cui R;Okada Y;Jang SG;Ku JL;Park JG;Kamatani Y;Hosono N;Tsunoda T;Kumar V;Tanikawa C;Kamatani N;Yamada R;Kubo M;Nakamura Y;Matsuda K
结直肠癌（CRC）是一种多因素疾病，环境和遗传因素都有助于其发展。在日本，CRC的发病率逐年上升。晚期结直肠癌患者预后差，但早期发现结直肠癌可改善临床结局。因此，确定影响CRC发展的流行病学因素将有助于预防或早期发现疾病。为了确定与结直肠癌风险相关的基因座，我们对1583例日本结直肠癌病例和1898例对照者进行了结直肠癌全基因组关联研究（GWAS）和肿瘤位置亚组分析。随后，我们进行了重复分析，共4809例CRC病例和2973例对照，包括225例韩国远端结肠癌患者和377例对照。我们在6 q26-q27区域发现了一个新的基因座（SLC 22 A3中的rs7758229，p=7.92×10−9，OR为1.28），该基因座与远端结肠癌显著相关。我们还复制了CRC与8 q24上SNP之间的关联（rs6983267和rs7837328，p=1.51×10−8和7.44×10−8，OR分别为1.18和1.17）。此外，我们发现三个遗传因素（SMAD 7中的rs7758229、rs6983267和rs 4939827）和一个环境因素（饮酒）的累积效应似乎使CRC风险增加了约两倍。我们在SLC 22 A3中发现了一个新的易感基因座，该基因座与亚洲人群远端结肠癌的风险有关。这些发现将进一步扩展我们对常见遗传变异在CRC病因学中的作用的理解。
Colorectal cancer (CRC) is a multifactorial disease with both environmental and genetic factors contributing to its development. The incidence of CRC is increasing year by year in Japan. Patients with CRC in advanced stages have a poor prognosis, but detection of CRC at earlier stages can improve clinical outcome. Therefore, identification of epidemiologial factors that influence development of CRC would facilitate the prevention or early detection of disease. To identify loci associated with CRC risk, we performed a genome-wide association study (GWAS) for CRC and sub-analyses by tumour location using 1583 Japanese CRC cases and 1898 controls. Subsequently, we conducted replication analyses using a total of 4809 CRC cases and 2973 controls including 225 Korean subjects with distal colon cancer and 377 controls. We identified a novel locus on 6q26-q27 region (rs7758229 in SLC22A3, p=7.92×10−9, OR of 1.28) that was significantly associated with distal colon cancer. We also replicated the association between CRC and SNPs on 8q24 (rs6983267 and rs7837328, p=1.51×10−8 and 7.44×10−8, ORs of 1.18 and 1.17, respectively). Moreover, we found cumulative effects of three genetic factors (rs7758229, rs6983267, and rs4939827 in SMAD7) and one environmental factor (alcohol drinking) which appear to increase CRC risk approximately twofold. We found a novel susceptible locus in SLC22A3 that contributes to the risk of distal colon cancer in an Asian population. These findings would further extend our understanding of the role of common genetic variants in the aetiology of CRC.
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影响因子：
5
作者：
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通讯作者：
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