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

Mohd Nizam, Zahary and Abdul Aziz, Ahmad Aizat and Gurjeet, Kaur (2015) Polymorphisms of cell cycle regulator genes CCND1 G870A and TP53 C215G: Association with colorectal cancer susceptibility risk in a Malaysian population. Oncology Letters, 10 (5). pp. 3216-3222. ISSN 17921074

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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). The A/A variant genotype of CCND1 and G/G variant genotype of TP53 exhibited a significantly greater association with the risk of sporadic CRC [CCND1: OR, 3.471; 95% confidence interval (CI), 1.443-8.350; P=0.005. TP53: OR, 2.829; CI, 1.119-7.152; P=0.026] as well as familial CRC susceptibility (CCND1: OR, 3.086; CI, 1.270-7.497; P=0.019. TP53: OR, 3.048; CI, 1.147-8.097; P=0.030). The results suggest a potential role of the SNPs CCND1 G870A and TP53 C215G in the modulation of sporadic and familial CRC susceptibility risk.

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