Risk of eighteen genome-wide association study-identified genetic variants for colorectal cancer and colorectal adenoma in Han Chinese

Abstract

BackgroundRecent genome-wide association studies (GWAS) identified eighteen single-nucleotide polymorphisms (SNPs) to be significantly associated with the risk of colorectal cancer (CRC). However, overall results of the following replications are inconsistent and little is known about whether these associations also exit in colorectal adenomas (CRA).MethodsThe SNP genotyping was performed using a Sequenom MassARRAY to investigate the association of these eighteen SNPs with colorectal neoplasm in a case-control study consisted of 1049 colorectal cancers, 283 adenomas, and 1030 controls.ResultsTwo of these SNPs, rs10505477 and rs719725, showed evidence of an association in both CRC and CRA in our study population. Besides, seven SNPs (rs10808555, rs7014346, rs7837328, rs704017, rs11196172, rs4779584, and rs7229639) were significantly associated with CRC, and another one SNP rs11903757 was over-represented in CRA compared with controls. The strongest association was provided by rs11196172 (OR = 2.02, 95% CI = 1.66 - 2.46, P < 0.0001) and rs11903757 (OR = 1.96, 95% CI = 1.28 - 3.00, P = 0.0026).ConclusionThese results suggest that some previously reported SNP associations also have impact on CRC and CRA predispositions in the Han Chinese population. A part of genetic risk to CRC is possibly mediated by susceptibility to adenomas.

Genetic Risk Score Is Associated With Prevalence of Advanced Neoplasms in a Colorectal Cancer Screening Population

“…So far, two studies examined this association and they found significant associations of GRS with risk for advanced adenomas indeed 28, 29 , but both studies included only a subset of the currently known common genetic variants. Other researchers found meaningful associations between single SNPs and the risk for AA in different study populations 30–32 . Nevertheless, one of those previous studies already found a stronger association of GRS with proximal neoplasms than distal neoplasms and hypothesized that – equivalent to germline mutations causing Lynch syndrome – many common genetic variants are also more closely related to neoplasms in the proximal colon compared to the distal colon 28 , a finding fully in line with our results.…”

Association between lncRNA CASC8 polymorphisms and the risk of cancer: a meta-analysis

“…Rs7837328 – another polymorphism in CASC8 – was associated with pCa and CRC susceptibility. 7 , 15 Although the above studies have reported the association between polymorphisms in the CASC8 gene and risks of cancer, the results were not consistent. Thus, the effect of polymorphisms in the CASC8 gene on cancer is still unclear.…”

“…The single-nucleotide polymorphism (SNP) of rs10505477 – located in the intron of the lncRNA of CASC8 gene – had an intimate correlation with CRC susceptibility,11–13 the risk of lung cancer, the prognosis for gastric cancer,14,6 and so on. Rs7837328 – another polymorphism in CASC8 – was associated with pCa and CRC susceptibility 7,15. Although the above studies have reported the association between polymorphisms in the CASC8 gene and risks of cancer, the results were not consistent.…”

SMAD7 rs4939827 variant contributes to colorectal cancer risk in Chinese population

“…Until recently, at least 6 independent case-control association studies have been conducted to investigate the association between rs4939827 and CRC risk in Chinese population. Three studies reported positive association results [ 15 , 19 – 20 ], and another three studies reported negative association results [ 21 – 23 ]. Until recently, three meta-analysis studies have been conducted [ 15 – 17 ].…”