Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 135, Issue 4, Pages 948-955Publisher
WILEY
DOI: 10.1002/ijc.28733
Keywords
Genome-wide association study; GWAS; colorectal cancer; SMAD7; genetic susceptibility; single-nucleotide polymorphisms; epidemiology
Categories
Funding
- US National Institutes of Health [R37CA070867, R01CA082729, R01CA124558, R01CA148667, R01CA122364]
- Vanderbilt University School of Medicine
- Shanghai Women's Health Study [R37CA070867]
- Shanghai Men's Health Study [R01CA082729]
- Shanghai Breast and Endometrial Cancer Studies [R01CA064277, R01CA092585]
- Guangzhou Colorectal Cancer Study (National Key Scientific and Technological Project) [2011ZX09307-001-04]
- National Basic Research Program [2011CB504303]
- Natural Science Foundation of China [81072383]
- Aichi Colorectal Cancer Study
- Grant for the Third Term Comprehensive Control Research for Cancer
- Japanese Ministry of Education, Culture, Sports, Science and Technology [17015018, 221S0001]
- Korea-NCC Colorectal Cancer Study (Basic Science Research Program through the National Research Foundation of Korea) [2010-0010276]
- Korea-NCC Colorectal Cancer Study (National Cancer Center Korea) [0910220]
- Japan-BioBank Colorectal Cancer Study (Ministry of Education, Culture, Sports, Science and Technology of the Japanese government)
- KCPS-II colorectal cancer study (National R&D Program for cancer control) [0920330]
- KCPS-II colorectal cancer study (Seoul RD Program) [10526]
- Korea-Seoul Colorectal Cancer Study
- Singapore Chinese Study [NMRC/1193/2008]
- Korea Health Promotion Institute [0910220] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- Grants-in-Aid for Scientific Research [221S0001] Funding Source: KAKEN
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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 x 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)
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