Polymorphisms of cell cycle regulator genes CCND1 G870A and TP53 C215G: Association with colorectal cancer susceptibility risk in a Malaysian population

Abstract

Abstract. Colorectal cancer (CRC) occurs as a more common sporadic form and a less common familial form. Our earlier analysis of germline mutations of mismatch repair genes confirmed only 32% of familial CRC cases as Lynch syndrome cases. It was hypothesized that the remaining familial aggregation may be 'polygenic' due to single nucleotide polymorphisms (SNPs) of low penetrance genes involved in cancer predisposition pathways, such as cell cycle regulation and apoptosis pathways. The current case-control study involving 104 CRC patients (52 sporadic and 52 familial) and 104 normal healthy controls investigated the contribution of the SNPs cyclin D1 (CCND1) G870A and tumor protein p53 (TP53) C215G in modulating familial and sporadic CRC susceptibility risk. DNA was extracted from peripheral blood and the polymorphisms were genotyped by employing a polymerase chain reaction-restriction fragment length polymorphism method. The association between these polymorphisms and CRC susceptibility risk was calculated using a binary logistic regression analysis and deriving odds ratios (ORs

Investigation of <em>cyclin D1</em> rs9344 G&gt;A polymorphism in colorectal cancer: a meta-analysis involving 13,642 subjects

“…High activity of CCND1 is common in a lot of human tumors 47,48. Several case–control studies have reported a positive signal of the CCND1 rs9344 G>A polymorphism with the risk of CRC;10–16 however, others have reported negative signal 17,18. Because of conflicting results and the insufficient sample size of individual studies, the final decision was far from certain.…”

“…Results of prior studies showed that the A allele of CCND1 rs9344 G>A resulted in an increasing level of mRNA (transcript-b) encoding CCND1 protein with an altered C-terminal domain 8,9. Results of some epidemiologic studies demonstrated that CCND1 rs9344 G>A polymorphism might confer CRC risk 10–18. Several meta-analyses showed that CCND1 rs9344 G>A polymorphism might be a risk factor for CRC, especially in the subgroups of sCRC and Caucasians 19–21.…”

TP53 Polymorphisms and Colorectal Cancer Risk in Patients with Lynch Syndrome in Taiwan: A Retrospective Cohort Study

“…Studies have reported an association of people with a Pro allele in their TP53 Arg72Pro (rs1042522) polymorphism with a decreased risk of sporadic CRC [31, 32, 33]. However, a case–control study reported no association of the TP53 polymorphism with CRC in patients with Lynch syndrome [34].…”