Modulation of human serum glutathione S‐transferase‐α concentration by cruciferous vegetable supplementation in a randomized, controlled feeding study is influenced by GSTM1 and GSTT1 genotypes

Glutathione S‐transferases (GST) detoxify a range of carcinogens. Isothiocyanates (ITC), from cruciferous vegetables (CF), are substrates for and inducers of GST. GST variants may alter ITC clearance such that response to CF varies by genotype. In a randomized cross‐over trial, we tested the hypothesis that changes in serum GST‐α concentration in response to CF feeding depend on GSTM1/GSTT1 genotype. 33 men and 34 women (age 20–40 yr), ate four 14‐day controlled diets: basal (vegetable‐free), and basal supplemented with 2 doses of CF, (1C and 2C) and CF plus apiaceous vegetables (1C+A), fed per kg BW. Fasting bloods from days 0, 7, 11 and 14 of each diet period, were analyzed for serum GST‐α by ELISA. GST‐α increased with 1C and 2C compared to basal diet (10% and 13%, respectively; P=0.02 and 0.004), but 1C+A did not differ from basal (P=0.59). Overall, GST‐α was higher in GSTM1‐null/T1‐null ( null/null ) than GSTM1 +/ T1 + (+/+) (4197 ± 338 and 3375 ± 183 pg/ml; P=0.03). The formal interaction of genotype‐by‐diet was not statistically significant, but the GST‐α increase during the 1C diet was among null/nulls (by 28%; P=0.008), and mainly null/null men (by 41%; P=0.01). GST‐α increased during the 2C diet in both null/null men (by 35%; P=0.04) and +/+ men (by 25%; P=0.01), but not in women. In summary, crucifer supplementation increased GST‐α, but the effect was most marked in GSTM1‐null/GSTT1‐null men. Supported by R01CA070913.