Genetic Polymorphisms Of Inflammation Response Genes And Their Influence On Malaysian Colorectal Cancer Patients : A Case Control Study
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Date
2012-05
Authors
Mustapha, Mohd Aminudin
Journal Title
Journal ISSN
Volume Title
Publisher
Universiti Sains Malaysia
Abstract
Sporadic colorectal cancer (CRC) is a complex and multi-factorial disease caused by the interaction of environmental and genetic predisposition factors. However the genetic susceptibility or predisposition risk of a certain individual to development of sporadic CRC remains largely undetermined. Recently chronic inflammation has been documented as a predisposing factor for CRC development. It was hypothesized that a pro-inflammatory genetic profile represented by genetic variation in inflammation response genes might be associated with increased susceptibility to CRC and a study was designed to test the hypothesis. Six polymorphisms of five genes involved in inflammation response such as IL-8 -251 T>A, TNF-α -308 G>A, ICAM-1 K469E, ICAM-1 R241G, IL-6 -174 G>C, and PPAR-γ 34 C>G were selected as candidate SNPs (Single Nucleotide Polymorphisms) to determine their influence, either singly or in combinations in mediating CRC susceptibility risk, with the final aim of identifying the at risk and/or protective genotypes. This case-control study, involved 510 study subjects with 255 histopathologically confirmed CRC patients as cases and 255 healthy normal individuals as controls. After getting informed consent, peripheral blood samples of all study subjects were collected, genomic DNA was extracted and genotyped employing Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and Allele Specific PCR, followed by sequencing. Genotypes were categorized into homozygous wild type, heterozygous and homozygous variants. Genotype frequencies and their risk associations were analyzed using statistical methods.
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Keywords
Genetic polymorphisms of inflammation response genes , their influence on Malaysian colorectal cancer patients