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

ABSTRACT: Recent 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).The 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.Two 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).These 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.

SUBMITTER: Tan C

PROVIDER: S-EPMC5363611 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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

Tan Chunwen C Hu Wangxiong W Huang Yanqin Y Zhou Jiaojiao J Zheng Shu S

Oncotarget 20161101 47

<h4>Background</h4>Recent 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).<h4>Methods</h4>The SNP genotyping was performed using a Sequenom MassARRAY to investigate the association of these eighteen SNPs with colo ...[more]

PMID: 27769063

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Project description:BackgroundSeveral genome-wide association studies (GWAS) involving European populations have successfully identified risk genetic variants associated with type 2 diabetes mellitus (T2DM). However, the effects conferred by these variants in Han Chinese population have not yet been fully elucidated.MethodsWe analyzed the effects of 24 risk genetic variants with reported associations from European GWAS in 3,040 Han Chinese subjects in Taiwan (including 1,520 T2DM cases and 1,520 controls). The discriminative power of the prediction models with and without genotype scores was compared. We further meta-analyzed the association of these variants with T2DM by pooling all candidate-gene association studies conducted in Han Chinese.ResultsFive risk variants in IGF2BP2 (rs4402960, rs1470579), CDKAL1 (rs10946398), SLC30A8 (rs13266634), and HHEX (rs1111875) genes were nominally associated with T2DM in our samples. The odds ratio was 2.22 (95% confidence interval, 1.81-2.73, P<0.0001) for subjects with the highest genetic score quartile (score>34) as compared with subjects with the lowest quartile (score<29). The incoporation of genotype score into the predictive model increased the C-statistics from 0.627 to 0.657 (P<0.0001). These estimates are very close to those observed in European populations. Gene-environment interaction analysis showed a significant interaction between rs13266634 in SLC30A8 gene and age on T2DM risk (P<0.0001). Further meta-analysis pooling 20 studies in Han Chinese confirmed the association of 10 genetic variants in IGF2BP2, CDKAL1, JAZF1, SCL30A8, HHEX, TCF7L2, EXT2, and FTO genes with T2DM. The effect sizes conferred by these risk variants in Han Chinese were similar to those observed in Europeans but the allele frequencies differ substantially between two populations.ConclusionWe confirmed the association of 10 variants identified by European GWAS with T2DM in Han Chinese population. The incorporation of genotype scores into the prediction model led to a small but significant improvement in T2DM prediction.

Dataset Information

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

Publications

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

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