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Genome‐wide association study identifies a new SMAD7 risk variant associated with colorectal cancer risk in East Asians
Author(s) -
Zhang Ben,
Jia WeiHua,
Matsuo Keitaro,
Shin Aesun,
Xiang YongBing,
Matsuda Koichi,
Jee Sun Ha,
Kim DongHyun,
Cheah Peh Yean,
Ren Zefang,
Cai Qiuyin,
Long Jirong,
Shi Jiajun,
Wen Wanqing,
Yang Gong,
Ji BuTian,
Pan ZhiZhong,
Matsuda Fumihiko,
Gao YuTang,
Oh Jae Hwan,
Ahn YoonOk,
Kubo Michiaki,
Thean Lai Fun,
Park Eun Jung,
Li HongLan,
Park Ji Won,
Jo Jaeseong,
Jeong JinYoung,
Hosono Satoyo,
Nakamura Yusuke,
Shu XiaoOu,
Zeng YiXin,
Zheng Wei
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28733
Subject(s) - colorectal cancer , medicine , oncology , genome wide association study , cancer , genetics , biology , gene , single nucleotide polymorphism , genotype
Genome‐wide association studies (GWAS) of colorectal cancer (CRC) have been conducted primarily in European descendants. In a GWAS conducted in East Asians, we first analyzed approximately 1.7 million single‐nucleotide polymorphisms (SNPs) in four studies with 1,773 CRC cases and 2,642 controls. We then selected 66 promising SNPs for replication and genotyped them in three independent studies with 3,612 cases and 3,523 controls. Five SNPs were further evaluated using data from four additional studies including up to 3,290 cases and 4,339 controls. SNP rs7229639 in the SMAD7 gene was found to be associated with CRC risk with an odds ratio (95% confidence interval) associated with the minor allele (A) of 1.22 (1.15–1.29) in the combined analysis of all 11 studies ( p = 2.93 × 10 −11 ). SNP rs7229639 is 2,487 bp upstream from rs4939827, a risk variant identified previously in a European‐ancestry GWAS in relation to CRC risk. However, these two SNPs are not correlated in East Asians ( r 2 = 0.008) nor in Europeans ( r 2 = 0.146). The CRC association with rs7229639 remained statistically significant after adjusting for rs4939827 as well as three additional CRC risk variants (rs58920878, rs12953717 and rs4464148) reported previously in this region. SNPs rs7229639 and rs4939827 explained approximately 1% of the familial relative risk of CRC in East Asians. This study identifies a new CRC risk variant in the SMAD7 gene, further highlighting the significant role of this gene in the etiology of CRC.