Association of CYP2E1 polymorphisms with gastrointestinal cancer in Malaysia

• Main Author: Chong, Eric Tzvy Jiann
• Format: Thesis
• Language: English
• Published: 2013
• Subjects: RC Internal medicine
• Online Access: https://eprints.ums.edu.my/id/eprint/17641/1/Association%20of%20CYP2E1%20polymorphisms.pdf; https://eprints.ums.edu.my/id/eprint/17641/
• Institution: Universiti Malaysia Sabah

Malaysia has a high mortality rate of gastrointestinal cancer (GIC) and hence finding a biomarker for GIC is crucial. CYP2E1 polymorphisms have been associated to increase the risk of GIC in many populations but remain unclear in Malaysian. This study was aimed to investigate the association between CYP2E1C -1019T and T7678A polymorphisms, as well as other risk factors such as age, ethnics, and gender to risk of GIC in Malaysia. DNA was extracted from 520 control and 175 GIC blood samples using alkaline lysis method, subjected to polymerase chain reaction followed by restriction fragment length polymorphism( PCR-RFLP)T. he SNPs were sequenced for confirmation. Cases and controls in both polymorphisms were found to be in Hardy-Weinberg equilibrium. In C-1019T SNP, the frequencies for c2 allele and c2/c2 genotype were 18.5% and 3.9%, respectively whereas the c2 allele and carrier with at least one c2 allele were found to significantly increase the risk to GIC by 1.38- and 1.45-fold, respectively. In contrast, the T7678A SNP revealed a frequency of 22.1% for C allele and 6.2% for C/C genotype in Malaysia. The T7678A SNP and combined C-1019T and T7678A SNPs did not contribute to GIC development in this study. Besides, elderly who aged >40 years old had a highly increased risk to GIC and Chinese showed greater risk to GIC when compared with the Malays, Indians and KadazanDusun but lower with other ethnic groups in Malaysia. It is worth to note that females were predominant to GIC and further investigation revealed that female had a 2.22- and 1.58-fold greater risk of gastric and colorectal cancers, respectively, when compared with males in Malaysia. In addition, the genotype distributions for both polymorphisms between Asian and non-Asian populations were significantly different. This study suggests that c2 allele and carrier with at least one c2 allele for C-1019T polymorphism may be used as a biomarker for GIC in Malaysia but further studies with larger sample size and including different gene-gene and gene-environmental interactions are needed