Interaction of methylenetetrahydrofolate reductase genotype and smoking habit in Taiwanese lung cancer patients.

摘要: The aim of this study was to evaluate the association and interaction genotypic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) environmental factors with lung cancer Taiwan. Two well- known polymorphic variants MTHFR, C677T (rs1801133) A1298C (rs1801131), were analyzed susceptibility, discussed their joint effects individual habits on risk. Patients Methods: In total, 358 patients 716 healthy controls recruited from China Medical Hospital central Taiwan genotyped. Results: MTHFR genotype, but not A1298C, differently distributed between control groups. T allele significantly more frequently found than patients. As for polymorphism, there no difference distribution Gene interactions smoking significant polymorphism. CT TT genotypes conferred a decreased risk 0.706 (95% confidence interval=0.531-0.939) cancer. Conclusion: Our results provide first evidence that C may be associated development novel useful marker primary prevention anticancer intervention. All over world, has become one most common malignancies (1, 2). Taiwan, is important its high incidence, mortality, low 5- year survival rate, especially female adenocarcinoma cases (3). Among well-known lifestyle-related causes cancer, considered (4-6). recent years, genomic susceptibilities among them used evaluation Primary candidates gene-environment studies are those encoding enzymes related metabolism established carcinogens. Methylenetetrahydrofolate key enzyme folate catalyzes 5, 10-methylene-tetrahydrofolate 5-methyltetra- hydrofolate. importance susceptibility arises involvement two pathways metabolism: leads numerous methylation processes dependent S-adenosyl-methionine (SAM), while other, via thymidylate synthesis, contributes DNA replication cell division. Reduced activity decrease homocysteine methionine turn level SAM, resulting hypomethylation. On other hand, reduced substrate, required synthesis could lead uracil misincorporation into DNA, diminished repair increased frequency chromosomal breaks damage. Malignancies derived rapidly proliferating tissues, which have higher requirement should susceptible deficiency resultant causing leukemia, lymphoma colorectal carcinoma. mechanism proposed explain these associations shunt versus thymidine purine would slow incorporation protect cells against carcinogenesis (7). Previous investigations genetic variations focused catalytic domain