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Meta-Analysis
. 2016 Nov 8;7(45):73945-73959.
doi: 10.18632/oncotarget.12154.

A comprehensive meta-analysis of genetic associations between five key SNPs and colorectal cancer risk

Yi Hong  1 , Guoying Wu  1 , Wei Li  1 , Dahai Liu  1 , Kan He  1   2
Affiliations
Meta-Analysis

A comprehensive meta-analysis of genetic associations between five key SNPs and colorectal cancer risk

Yi Hong et al. Oncotarget. .

Abstract

Genome-wide association studies (GWAS) on colorectal cancer (CRC) have identified dozens of single nucleotide polymorphisms (SNPs) in more than 19 independent loci associated with CRC. Due to the heterogeneity of the studied subjects and the contrary results, it is challenging to verify the certainty of the association between these loci and CRC.We conducted a critical review of the published studies of SNPs associated with CRC. Five most frequently reported SNPs, which are rs6983267/8q24.21, rs4939827/18q21.1, rs10795668/10p14, rs4444235/14q22.2 and rs4779584/ 15q13.3, were selected for the current study from the qualified studies. Then meta-analyses based on larger sample sizes with average of 33,000 CRC cases and 34,000 controls were performed to assess the association between SNPs and CRC risk. Heterogeneity among studies and publication bias were assessed by the χ2-based Q statistic test Begg's funnel plot or Egger's test, respectively.Our meta-analysis confirmed significant associations of the five SNPs with CRC risk under different genetic models. Two risk variants at rs6983267 {Odds Ratio (OR) 1.388, 95% Confidence Interval (CI) 1.180-1.8633} and rs10795668 (OR 1.323, 95% CI 1.062-1.648) had the highest ORs in homogeneous model. While ORs of the other three variants at rs4939827 {OR 1.298, 95% CI 1.135-1.483}, rs4779584 (OR 1.261, 95% CI 1.146-1.386) and rs4444235 (OR 1.160, 95% CI 1.106-1.216) were also statistically significant. Sensitivity analyses and publication bias assessment indicated the robust stability and reliability of the results.

Keywords: GWAS; colorectal cancer; meta-analysis; single nucleotide polymorphism.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1. Flow chart of study selection on rs6983267
Figure 2
Figure 2. Location of five SNPs selected for meta-analysis
Adopted from NCBI Variation Viewer 1.5.
Figure 3
Figure 3. Forest plots for the 5 SNPs and risk of CRC in the homogenous model
A. rs6938267, B. rs4939827, C. rs10795668, D. rs4444235, E. rs4779584.
Figure 4
Figure 4. Begg's Funnel plot of 5 SNPs for Publication bias in the homogenous model
a. rs6938267, b. rs4939827, c. rs10795668, d. rs4444235, e. rs4779584.
Figure 5
Figure 5. Sensitivity analysis of the odds ratio coefficients under dominant (a, c) and homogeneous (b, d, e) genetic models
a. rs6938267, b. rs4939827, c. rs10795668, d. rs4444235, e. rs4779584.
See this image and copyright information in PMC

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