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http://dx.doi.org/10.7314/APJCP.2013.14.2.619

Contribution of the MLH1 -93G>A Promoter Polymorphism in Modulating Susceptibility Risk in Malaysian Colorectal Cancer Patients  

Nizam, Zahary Mohd (Human Genome Centre, USM)
Abdul Aziz, Ahmad Aizat (Human Genome Centre, USM)
Kaur, Gurjeet (Institute for Research in Molecular Medicine (INFORMM), USM)
Abu Hassan, Muhammad Radzi (Internal Medicine Department, Hospital Sultanah Bahiyah)
Mohd Sidek, Ahmad Shanwani (Surgical Department, Hospital Raja Perempuan Zainab II)
Lee, Yeong Yeh (Department of Medicine, School of Medical Sciences, USM Health Campus)
Mazuwin, Maya (Department of Surgery, School of Medical Sciences, USM Health Campus)
Ankathil, Ravindran (Human Genome Centre, USM)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.14, no.2, 2013 , pp. 619-624 More about this Journal
Abstract
Background: Colorectal cancer (CRC) exists in a more common sporadic form and less common hereditary forms, associated with the Lynch syndrome, familial adenomatous polyposis (FAP) and other rare syndromes. Sporadic CRC is believed to arise as a result of close interaction between environmental factors, including dietary and lifestyle habits, and genetic predisposition factors. In contrast, hereditary forms such as those related to the Lynch syndrome result from inheritance of germline mutations of mismatch repair (MMR) genes. However, in certain cases, the influence of low penetrance alleles in familial colorectal cancer susceptibility is also undeniable. Aim: To investigate the genotype frequencies of MLH1 promoter polymorphism -93G>A and to determine whether it could play any role in modulating familial and sporadic CRC susceptibility risk. Methods: A case-control study comprising of 104 histopathologically confirmed CRC patients as cases (52 sporadic CRC and 52 Lynch syndrome patients) and 104 normal healthy individuals as controls was undertaken. DNA was extracted from peripheral blood and the polymorphism was genotyped employing PCR-RFLP methods. The genotypes were categorized into homozygous wild type, heterozygous and homozygous variants. The risk association between these polymorphisms and CRC susceptibility risk was calculated using binary logistic regression analysis and deriving odds ratios (ORs). Results: When risk association was investigated for all CRC patients as a single group, the heterozygous (G/A) genotype showed a significantly higher risk for CRC susceptibility with an OR of 2.273, (95%CI: 1.133-4.558 and p-value=0.021). When analyzed specifically for the 2 types of CRC, the heterozygous (G/A) genotype showed significantly higher risk for sporadic CRC susceptibility with and OR of 3.714, (95%CI: 1.416-9.740 and p-value=0.008). Despite high OR value was observed for Lynch syndrome (OR: 1.600, 95%CI: 0.715-3.581), the risk was not statistically significant (P=0.253). Conclusion: Our results suggest an influence of MLH1 promoter polymorphism -93G>A in modulating susceptibility risk in Malaysian CRC patients, especially those with sporadic disease.
Keywords
Colorectal cancer; Lynch syndrome; MLH1 -93G>A; sporadic cases; Malaysia;
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