GLUTATHIONE-S-TRANSFERASE MU-GENOTYPE, DIET, AND SMOKING AS DETERMINANTS OF SISTER-CHROMATID EXCHANGE FREQUENCY IN LYMPHOCYTES

Polymorphisms in inherited metabolic traits and intake of dietary anti oxidants have been reported to be associated with risk for the develop ment of lung cancer in smokers, This increased risk of lung cancer is presumably attributable to the accumulation of DNA damage, We conducte d a study to investigate whether genetic metabolic variants and antiox idant consumption affected the sister chromatid exchange (SCE) level i n lymphocytes. Study subjects were 78 friends and spouses of cases fro m a case-control study of lung cancer designed to investigate the asso ciation of metabolic polymorphisms with lung cancer, The metabolic tra its studied included glutathione S-transferase class mu and variants o f P-450 isoenzymes CYP1A1 and CYP2D6. Intake of antioxidants including vitamins A, C, and E and selenium was determined through the administ ration of a validated, semiquantitative food frequency questionnaire, Detailed information on smoking, family history of cancer, medical his tory, and environmental and occupational exposures was also obtained i n an interviewer-administered questionnaire, Smoking status was found to be significantly associated with SCE frequency, In addition, SCE fr equency decreased with the period of time since quitting smoking, The presence of one or more glutathione S-transferase class mu alleles was associated with significantly lower SCE, Higher intake of vitamin A a nd selenium was also inversely associated with SCE level, Thus, the re sults suggest that glutathione Stransferase class mu and the intake of vitamin A and selenium may modulate the accumulation of chromosomal d amage in lymphocytes.