Abstract
BackgroundAlthough mounting non-hereditary colorectal cancer (NHCRC) associated single nucleotide polymorphisms (SNPs) have been observed, no field synopsis and meta-analysis has been conducted through systematically assessing cumulative evidence, during the past 5 years.MethodsWe retrieved the database via the PubMed, Web of Science and Embase gateways to identify publications concerning the associations between SNPs and risk of NHCRC, up to May 1st, 2017. To assess the finding credibility, cumulative evidence was graded based on the Venice criteria. Meta-analysis was also performed for three subgroups including ethnicity (Asian vs Caucasian), primary cancer site (colon vs rectum) and TNM stage (I II vs III IV). Then, we arranged those high quality SNPs into different regions according to their locations on genes to evaluate their functional roles on CRC development.Results5114 publications were collected and 1001 of them met our inclusion criteria, which totally included 1788 SNPs in 793 genes or distinct chromosomal loci. Totally, we performed 359 primary and subgroup meta-analyses for 160 SNPs in 96 distinct genes. By utilizing the Venice criteria, we identified 15 high quality SNPs with 25 high credibility significant associations. Furthermore, we artificially divided the high quality SNPs into different groups, based on their SNP loci (exon region, intron region, promoter region, downstream region, non-coding region and intergenic region).ConclusionWe have identified 15 high quality SNPs which may act as promising genetic biomarkers for clinical NHCRC susceptibility screening and explored their functional roles on the NHCRC development based on their locations on genes.
Highlights
Mounting non-hereditary colorectal cancer (NHCRC) associated single nucleotide polymorphisms (SNPs) have been observed, no field synopsis and meta-analysis has been conducted through systematically assessing cumulative evidence, during the past 5 years
In the present systematic review and meta-analysis, we focus on the high quality Single nucleotide polymorphism (SNP) in the field of genetic predisposition to NHCRC, involving the correlations of SNPs with ethnicity, primary cancer site and TNM stage (I II or III IV)
In this article, we systematically reviewed the associations between 160 SNPs in 96 distinct genes or chromosomal loci and predisposition to NHCRC or to subgroups identified by ethnicity (Asian vs Caucasian), primary cancer site, TNM stage (I II vs III IV) and SNP locations on genes, with the quality assessment of cumulative evidence, and 15 high quality SNPs were confirmed
Summary
Mounting non-hereditary colorectal cancer (NHCRC) associated single nucleotide polymorphisms (SNPs) have been observed, no field synopsis and meta-analysis has been conducted through systematically assessing cumulative evidence, during the past 5 years. It’s worth noting that, there have existed two comprehensive field meta-analyses which demonstrated all CRC risk associated variants, up to 2012, providing directions for future investigators [3, 4]. Inspired by these two articles, we noticed that SNP plays an essential role in the genetic predisposition of CRC, constituting nearly 80% of he significant genetic variants which include the insertion/deletion polymorphism and variable number of tandem repeat (VNTR). What’s more, no studies mentioned the role of the whole associated SNPs on CRC development, based on their locations on genes
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