Short Communication Modulation of Human Serum Glutathione S-Transferase A1/2 Concentration by Cruciferous Vegetables in a Controlled Feeding Study Is Influenced by GSTM1 and GSTT1 Genotypes

Glutathione S-transferases (GST) detoxify a wide range of carcinogens. Isothiocyanates (ITC), from cru-ciferous vegetables, are substrates for and inducers of GST. GST variants may alter ITC clearance such that response to crucifers varies by genotype. In a ran-domized cross-over trial, we tested the hypothesis that changes in serum GSTA1/2 concentration in re-sponse to cruciferous vegetable feeding depends on GSTM1/GSTT1 genotype. Thirty-three men and 34 women (age 20-40 years) ate four 14-day controlled diets—basal (vegetable-free), basal supplemented with two different doses of crucifers (“single dose” and “double dose”), and single-dose cruciferous-plus-apiaceous vegetables—fed per kilogram of body weight. Fasting bloods from days 0, 7, 11, and 14 of each diet period were analyzed for serum GSTA1/2 by ELISA. GSTA1/2 increased with single- and double-dose cruciferous compared with basal diet (10 % and 13%, respectively; P = 0.02 and 0.004), but cruciferous-plus-apiaceous did not differ from basal (P = 0.59). Overall, GSTA1/2 was higher in GSTM1-null/GSTT1-null than GSTM1+/GSTT1+ individuals (4,198 ± 338 and 3,372 ± 183 pg/mL; P = 0.03). The for-mal interaction of genotype-by-diet was not statisti-cally significant, but the GSTA1/2 increase during the single-dose cruciferous diet was among GSTM1-null/GSTT1-null individuals (by 28%; P = 0.008), largely explained by GSTM1-null/GSTT1-null men (by 41%; P = 0.01). GSTA1/2 increased during the double-dose cruciferous diet in both GSTM1-null/ GSTT1-null men (by 35%; P = 0.04) and GSTM1+/ GSTT1+ men (by 26%; P = 0.01) but not in women. In summary, cruciferous vegetable supplementation increased GSTA1/2, but the effect was most marked in GSTM1-null/GSTT1-null men. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2974–8