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

Thean, LF and Li, HH and Teo, YY and Koh, WP and Yuan, JM and Teoh, ML and Koh, PK and Tang, CL and Cheah, PY (2012) Association of Caucasian-identified variants with colorectal cancer risk in Singapore Chinese. PLoS ONE, 7 (8).

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Abstract

Background: Genome-wide association studies (GWAS) in Caucasians have identified fourteen index single nucleotide polymorphisms (iSNPs) that influence colorectal cancer (CRC) risk. Methods: 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. Results: 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. Conclusions: 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. © 2012 Thean et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Thean, LF
Li, HH
Teo, YY
Koh, WP
Yuan, JMyuanj@pitt.eduYUANJ
Teoh, ML
Koh, PK
Tang, CL
Cheah, PY
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorEwart Toland, AmandaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, or Units > Pittsburgh Cancer Institute
Date: 3 August 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 8
DOI or Unique Handle: 10.1371/journal.pone.0042407
Schools and Programs: Graduate School of Public Health > Epidemiology
Refereed: Yes
Other ID: NLM PMC3411754
PubMed Central ID: PMC3411754
PubMed ID: 22879968
Date Deposited: 18 Oct 2012 16:47
Last Modified: 16 Mar 2019 14:55
URI: http://d-scholarship.pitt.edu/id/eprint/15881

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