Yongchao Lu1, Mingfeng Cao2, Kejian Gao3, Jinjiao Jiang4, Xuewen Shi5. 1. Department of Traditional Chinese Medicine, Shandong Provincial Hospital Affiliated to Shandong University Jinan 250021, China. 2. Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University Jinan 250021, China. 3. Department of Anorectal Surgery, Central Hospital of Jinan City Jinan 250014, China. 4. Department of Intensive Care Unit, Shandong Provincial Hospital Affiliated to Shandong University Jinan 250021, China. 5. Department of Anorectal Surgery, Hospital Affiiated to Shandong University of Traditional Chinese Medicine Jinan, China.
Abstract
OBJECTIVE: O(6)-methylguanine DNA methyl-transferase gene (MGMT) is a central DNA repair mechanism with a significant role in removing DNA damage caused by alkylating agents and inhibiting human oncogenesis. Two single polymorphisms in the MGMT gene, Leu84Phe and Ile143Val, have been reported to affect DNA repair capability and enzymic activity, thereby leading to formation of different cancers. In this work, we quantitatively assess the associations between MGMT polymorphisms and risk of colorectal cancer (CRC), as previous studies has implicated inconsistencies in their results. METHODS: Analysis was performed on all usable data collected from the eligible studies that were searched in multiple bibliographical databases (PubMed, SCOPUS, and Embase). RESULTS: We obtained studies on Leu84Phe and Ile143Val, providing 6,154 and 7,371 samples, respectively. In the analysis on Leu84Phe, the SNP presented no global association with CRC at both the genotypic and the allelic level, but a trend towards an increased or decreased risk was shown in the models examined. Stratification by ethnicity revealed a significant increase in risk of CRC related to the Phe/Phe genotype in Caucasian samples (homozygote genetic model: OR=1.70, 95% CI=1.06-2.72; recessive genetic model: OR=1.80, 95% CI=1.12-2.87). CONCLUSIONS: Based on the statistical data, our meta-analysis indicates that Leu84Phe polymorphism in the MGMT gene may predispose Caucasians to CRC.
OBJECTIVE:O(6)-methylguanine DNA methyl-transferase gene (MGMT) is a central DNA repair mechanism with a significant role in removing DNA damage caused by alkylating agents and inhibiting human oncogenesis. Two single polymorphisms in the MGMT gene, Leu84Phe and Ile143Val, have been reported to affect DNA repair capability and enzymic activity, thereby leading to formation of different cancers. In this work, we quantitatively assess the associations between MGMT polymorphisms and risk of colorectal cancer (CRC), as previous studies has implicated inconsistencies in their results. METHODS: Analysis was performed on all usable data collected from the eligible studies that were searched in multiple bibliographical databases (PubMed, SCOPUS, and Embase). RESULTS: We obtained studies on Leu84Phe and Ile143Val, providing 6,154 and 7,371 samples, respectively. In the analysis on Leu84Phe, the SNP presented no global association with CRC at both the genotypic and the allelic level, but a trend towards an increased or decreased risk was shown in the models examined. Stratification by ethnicity revealed a significant increase in risk of CRC related to the Phe/Phe genotype in Caucasian samples (homozygote genetic model: OR=1.70, 95% CI=1.06-2.72; recessive genetic model: OR=1.80, 95% CI=1.12-2.87). CONCLUSIONS: Based on the statistical data, our meta-analysis indicates that Leu84Phe polymorphism in the MGMT gene may predispose Caucasians to CRC.
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