Glutathione S-transferase genotype as a susceptibility factor in smoking-related coronary heart disease

Cancer studies suggest that the null polymorphisms of glutathione S-transfe rase M1 or T1 (GSTM1/GSTT1) may affect the ability to detoxify or activate chemicals in cigarette smoke. The potential modification of the association between smoking and coronary heart disease (CHD) by GSTM1 and GSTT1 has no t been studied in humans. A case-cohort study was conducted to test the hyp otheses that specific genotypes of GSTM1 or GSTT1 affect susceptibility to smoking-related CHD. CHD cases (n = 400) accrued during 1987-1993 and a coh ort-representative sample (n = 924) were selected from a biracial cohort of 15 792 middle-aged men and women in four US communities. A significantly h igher frequency of GSTM1-0 and a lower frequency of GSTT1-0 were found in w hites (GSTM1-0 = 47.1%, GSTT1-0 = 16.4%) than in African-Americans (AAs) (G STM1-0 = 17.5%, GSTT1-0 = 25.9%). A smoking-GSTM1-0 interaction for the ris k of CHD was statistically significant on an additive scale, with ever-smok ers with GSTM1-0 at a approximate to 1.5-fold higher risk relative to ever- smokers with GSTM1-1 and a approximate to 2-fold higher risk relative to ne ver-smokers with GSTM1-0, after adjustment for other CHD risk factors. The interaction between having smoked greater than or equal to 20 pack-years an d GSTT1-1 was statistically significant on both multiplicative and additive scales. The risk of CHD given both GSTT1-1 and greater than or equal to 20 pack-years of smoking was approximate to three times greater than the risk given exposure to greater than or equal to 20 pack-years of smoking alone, and approximate to four times greater than the risk given exposure to GSTT 1-1 alone. The modification of the smoking-CHD association by GSTM1 or GSTT 1 suggests that chemicals in cigarette smoke that are substrates for glutat hione S-transferases may be involved in the etiology of CHD. (C) 2000 Elsev ier Science Ireland Ltd. All rights reserved.