Genome-wide association study identifies a new SMAD7 risk variant associated with colorectal cancer risk in East Asians.
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.
Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN.
Ben
B
Zhang
Wei-Hua
WH
Jia
Keitaro
K
Matsuo
Aesun
A
Shin
Yong-Bing
YB
Xiang
Koichi
K
Matsuda
Sun Ha
SH
Jee
Dong-Hyun
DH
Kim
Peh Yean
PY
Cheah
Zefang
Z
Ren
Qiuyin
Q
Cai
Jirong
J
Long
Jiajun
J
Shi
Wanqing
W
Wen
Gong
G
Yang
Bu-Tian
BT
Ji
Zhi-Zhong
ZZ
Pan
Fumihiko
F
Matsuda
Yu-Tang
YT
Gao
Jae Hwan
JH
Oh
Yoon-Ok
YO
Ahn
Michiaki
M
Kubo
Lai Fun
LF
Thean
Eun Jung
EJ
Park
Hong-Lan
HL
Li
Ji Won
JW
Park
Jaeseong
J
Jo
Jin-Young
JY
Jeong
Satoyo
S
Hosono
Yusuke
Y
Nakamura
Xiao-Ou
XO
Shu
Yi-Xin
YX
Zeng
Wei
W
Zheng
D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D015179:Colorectal Neoplasms / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D056910:Republic of Korea; D012306:Risk; D012846:Singapore; D051906:Smad7 Protein / Q000235:genetics*
C497806:SMAD7 protein, human; D051906:Smad7 Protein
GWAS; Genome-wide association study; SMAD7; colorectal cancer; epidemiology; genetic susceptibility; single-nucleotide polymorphisms