Association of Caucasian-identified variants with colorectal cancer risk in Singapore Chinese

• Published in: PloS one Vol. 7; no. 8; p. e42407
• Main Authors: Thean, Lai Fun, Li, Hui Hua, Teo, Yik Ying, Koh, Woon-Puay, Yuan, Jian-Min, Teoh, Mei Lin, Koh, Poh Koon, Tang, Choong Leong, Cheah, Peh Yean
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03-08-2012; Public Library of Science (PLoS)
• Subjects: Age; Aged; Aged, 80 and over; Asian Continental Ancestry Group - genetics; Biology; Bone morphogenetic proteins; Cancer; Cancer research; Case-Control Studies; Chromosomes; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Colorectal surgery; European Continental Ancestry Group - genetics; Family medical history; Female; Gender; Genetic Predisposition to Disease; Genomes; Health aspects; Health care; Health risks; Hospitals; Humans; Linkage disequilibrium; Linkage Disequilibrium - genetics; Male; Medical screening; Medicine; Middle Aged; Polymorphism, Single Nucleotide - genetics; Population; Principal components analysis; Public health; Rectum; Risk; Risk Factors; Singapore; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Statistical analysis; White people; Singapore
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0042407

Genome-wide association studies (GWAS) in Caucasians have identified fourteen index single nucleotide polymorphisms (iSNPs) that influence colorectal cancer (CRC) risk.
We investigated the role of eleven iSNPs or surrogate SNPs (sSNPs), in high linkage disequilibrium (LD, r(2)≥ 0.8) and within 100 kb vicinity of iSNPs, in 2,000 age- and gender-matched Singapore Chinese (SCH) cases and controls.
Only iSNP rs6983267 at 8q24.21 and sSNPs rs6695584, rs11986063, rs3087967, rs2059254, and rs7226855 at 1q41, 8q23.3, 11q23.1, 16q22.1 and 18q21.1 respectively showed evidence of association with CRC risk, with odds ratios (OR) ranging from 1.13 to 1.40. sSNP rs827401 at 10p14 was associated with rectal cancer risk (OR = 0.74, 95% CI 0.63-0.88) but not disease prognosis (OR = 0.91, 95% CI 0.69-1.20). Interestingly, sSNP rs3087967 at 11q23.1 was associated with CRC risk in men (OR = 1.34, 95% CI 1.14-1.58) but not women (OR = 1.07, 95% CI: 0.88-1.29), suggesting a gender-specific role. Half of the Caucasian-identified variants, including the recently fine-mapped BMP pathway loci, BMP4, GREM1, BMP2 and LAMA 5, did not show any evidence for association with CRC in SCH (OR ~1; p-value >0.1). Comparing the results of this study with that of the Northern and Hong Kong Chinese, only variants at chromosomes 8q24.21, 10p14, 11q23.1 and 18q21.1 were replicated in at least two out of the three Chinese studies.
The contrasting results between Caucasians and Chinese could be due to different LD patterns and allelic frequencies or genetic heterogeneity. The results suggest that additional common variants contributing to CRC predisposition remained to be identified.