Dataset Information

The association of a genetic variant in CDKN2A/B gene and the risk of colorectal cancer.

ABSTRACT: Colorectal cancer is among the most aggressive tumors, and its development involves an interplay between various genetic and environmental familial risk factors. Several genetic polymorphisms have been reported to be associated with colorectal cancer in recent studies. In this current study, we aimed to evaluate the possible relationship between a CDKN2A/B, single nucleotide polymorphisms (SNP) (rs10811661), with the risk of colorectal cancer. A total of 541 individuals with, or without cancer were recruited. DNA was extracted, and genotyped using a Taq-Man based real-time PCR method. The rs10811661 SNP was associated with an increased risk of colorectal cancer (additive model: OR=3.46, CI= 1.79-6.69, p<0.0001 and recessive model: 5.72, CI= 3.12-10.49, p<0.0001). The distribution of minor alleles in the total population for homozygote allele was 9.2 %, while this was 20.1 % for heterozygotes. In summary, our findings indicate that the rs10811661 polymorphism of the CDKN2A/B gene was strongly related to the occurrence of colorectal cancer suggesting its potential role as a prognostic biomarker for the management of colorectal cancer.

SUBMITTER: Rahmani F

PROVIDER: S-EPMC7588726 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The association of a genetic variant in CDKN2A/B gene and the risk of colorectal cancer.

Rahmani Farzad F Avan Amir A Amerizadeh Forouzan F Ferns Gordon A GA Talebian Sahar S Shahidsales Soodabeh S

EXCLI journal 20200914

Colorectal cancer is among the most aggressive tumors, and its development involves an interplay between various genetic and environmental familial risk factors. Several genetic polymorphisms have been reported to be associated with colorectal cancer in recent studies. In this current study, we aimed to evaluate the possible relationship between a CDKN2A/B, single nucleotide polymorphisms (SNP) (rs10811661), with the risk of colorectal cancer. A total of 541 individuals with, or without cancer w ...[more]

PMID: 33122978

Similar Datasets

Project description:Genome-wide association studies have reported 56 independently associated colorectal cancer (CRC) risk variants, most of which are non-coding and believed to exert their effects by modulating gene expression. The computational method PrediXcan uses cis-regulatory variant predictors to impute expression and perform gene-level association tests in GWAS without directly measured transcriptomes. In this study, we used reference datasets from colon (n?=?169) and whole blood (n?=?922) transcriptomes to test CRC association with genetically determined expression levels in a genome-wide analysis of 12,186 cases and 14,718 controls. Three novel associations were discovered from colon transverse models at FDR???0.2 and further evaluated in an independent replication including 32,825 cases and 39,933 controls. After adjusting for multiple comparisons, we found statistically significant associations using colon transcriptome models with TRIM4 (discovery P?=?2.2?×?10-?4, replication P?=?0.01), and PYGL (discovery P?=?2.3?×?10-?4, replication P?=?6.7?×?10-?4). Interestingly, both genes encode proteins that influence redox homeostasis and are related to cellular metabolic reprogramming in tumors, implicating a novel CRC pathway linked to cell growth and proliferation. Defining CRC risk regions as one megabase up- and downstream of one of the 56 independent risk variants, we defined 44 non-overlapping CRC-risk regions. Among these risk regions, we identified genes associated with CRC (P?<?0.05) in 34/44 CRC-risk regions. Importantly, CRC association was found for two genes in the previously reported 2q25 locus, CXCR1 and CXCR2, which are potential cancer therapeutic targets. These findings provide strong candidate genes to prioritize for subsequent laboratory follow-up of GWAS loci. This study is the first to implement PrediXcan in a large colorectal cancer study and findings highlight the utility of integrating transcriptome data in GWAS for discovery of, and biological insight into, risk loci.

Dataset Information

The association of a genetic variant in CDKN2A/B gene and the risk of colorectal cancer.

Publications

The association of a genetic variant in CDKN2A/B gene and the risk of colorectal cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets