Genetic Polymorphisms of Cytochrome P450 1A1, Glutathion S-transferases M1, P1 and Methylenetetrahydrofolate Reductase, and Risk of Lung Cancer：A Nested Case-control Study

• Main Authors: Yi-Lin Jeng, 鄭義麟
• Other Authors: Chien-An Sun
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/88481918847313762820

碩士 === 國防醫學院 === 公共衛生學研究所 === 91 === Metabolic enzymes involved in either the activation or detoxification of chemical carcinogens in tobacco smoke and enzymes involved in folate metabolism that is thought to influence DNA methylation and nucleotide synthesis have received a great deal of attention as possible genetic susceptibility factors for a variety of cancers. Therefore, the investigator hypothesized that variant genotypes of CYP1A1, GSTM1, GSTP1, and MTHFR may play a role in the etiology of lung cancer. To test this hypothesis, we conducted a nested case-control study of 59 incident lung cancer cases diagnosed between 1991 and 2000 and 232 healthy controls selected from participants of a Community-Based Cancer Screening Project’s cohort in Taiwan. Smoking status were obtained by a structured questionnaire and genotypes of CYP1A1-m1, GSTM1, GSTP1-A313G, and MTHFR-C677T were determined by PCR-PFLP. Logistic regression analyses were used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for each relevant genotype. Study results showed that the allele frequencies of CYP1A1-m1, GSTM1 null genotype, GSTP1-A313G, and MTHFR-C677T in controls were 0.42, 0.61, 0.18, and 0.27, respectively. There was a statistically significant relationship between wt/m1 or m1/m1 genotypes of CYP1A1-m1 and decreased risk of lung cancer (wt/wt genotype as the referent group, OR=0.38, 95% CI=0.21-0.69), while no evidence was found for significant associations between genetic polymorphisms in GSTM1, GSTP1-A313G, and MTHFR-C677T and lung cancer risk. Although not providing any information about the mechanism of action, the current study results do indicate that individuals who have a variant genotype of CYP1A1 may be at decreased risk of lung cancer. By identifying specific compounds that may be metabolized by CYP1A1, novel pathways of lung carcinogenesis may be identified.