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

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.

Association between 8q24 rs6983267 polymorphism and cancer susceptibility: a meta-analysis involving 170,737 subjects

“…[ 61 ] was carried out in Caucasians, while it was incorporated into the Asian subgroup in a previous meta-analysis [ 17 ]; 2) we included 7 case-control studies in Asians, instead of only 4 studies in a meta-analysis by Haerian et al . [ 18 ], and therefore, results of our meta-analysis were more credible; 3) lack of further research in different stratified analyses prevented comprehensive understanding in a recent meta-analysis [ 21 ]; 4) our results were based on sufficient evidence, which was proved by FPRP for the first time.…”

“…Besides, such contradictions also existed in some other meta-analyses [ 17 – 19 ]. Of note, lack of further evaluation in different stratified analyses prevented comprehensive understanding in some recent meta-analyses [ 20 , 21 ]. To better understand the precise relationship, we performed a comprehensive meta-analysis with increased statistical power.…”

Japanese genome‐wide association study identifies a significant colorectal cancer susceptibility locus at chromosome 10p14

“…These independent whole genome‐wide association studies both found loci on 10p14 to be commonly associated with CRC. We consider this 10p14 locus to be a significant region of CRC susceptibility because it was identified in multiple studies in more than one race, including European and Japanese populations . Recently, a significant interaction between an SNP at 10p14 (rs4143094) and processed meat consumption was also reported in CRC patients …”

“…We consider this 10p14 locus to be a significant region of CRC susceptibility because it was identified in multiple studies in more than one race, including European and Japanese populations. (29,30) Recently, a significant interaction between an SNP at 10p14 (rs4143094) and processed meat consumption was also reported in CRC patients. (31) We performed data mining for genes that exist in this susceptibility locus in order to investigate the mechanism by which these SNP are connected to the causes of CRC.…”

SMAD7 rs4939827 variant contributes to colorectal cancer risk in Chinese population

“…If there is no significant heterogeneity, the pooled OR is calculated by a fixed effect model; otherwise by a random-effect model [15–17, 28–30, 35–41]. Z test is used to determine the significance of pooled OR [28–30].…”