Genetic Polymorphisms in Cytochrome P450 2E1 and Methylenetetrahydrofolate Reductase and Risk of Hepatocellular Carcinoma-- A Nested Case-Control Study

• Main Authors: Huang, Chiao-Ting, 黃喬婷
• Other Authors: Chen Chien-Jen
• Format: Others
• Language: zh-TW
• Published: 1998
• Online Access: http://ndltd.ncl.edu.tw/handle/53562651881304941955

碩士 === 國立臺灣大學 === 流行病學研究所 === 86 === Objectives. The relationship between genetic polymorphisms in enzymes involved in nutrient/carcinogen metabolism and risk of cancer has recently received attention. This study was carried out to investigate whether cytochrome P450 2E1 (CYP2E1) and methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms were related to susceptibility to hepatocellular carcinoma (HCC). Methods. Genotyping of CYP2E1 was performed using polymerase chain reaction-based restriction fragment length polymorphism on peripheral leukocyte DNA from 80 HCC cases and 437 controls nested within a cohort study of 7342 men. A total of 76 HBsAg-positive HCC cases and 163 HBsAg-positive controls were also tested for MTHFR genetic polymorphism. Results. The adjusted odds ratio (OR) for the CYP2E1 predominant homozygous c1/c1 genotype detected by RsaI digestion was 2.0 (95% confidence interval [CI]1.1-3.5). There was no notable interaction between CYP2E1 polymorphism and cigarette smoking or alcohol drinking in HCC risk compared with individuals having the heterozygous genotype c1/c2 or rare genotype c2/c2; however, significantly elevated HCC risk was found only among homozygotes of c1/c1 genotype who had habits of smoking and drinking. A synergistic effect on HCC risk was observed for the susceptible genotype of CYP2E1 with chronic liver disease and a family history of HCC in first degree relatives. No overall association between MTHFR genetic polymorphism and HCC was observed, but MTHFR val/val genotype interacts with the history of liver diseases and CYP2E1 genotype. The most striking OR for HCC was obverved among chronic hepatitis B carriers with the variant homozygous val/val genotype of MTHFR and past history of liver diseases (OR=10.3, 95%CI 1.1-95.6). Conclusions. Homozygosity for the c1/c1 genotype of CYP2E1 was associated with increased risk of HCC. This study suggested that further evaluation of MTHFR genetic polymorphism as a susceptibility factor for HCC is warranted.