Glutathione S-transferases (GSTs), a superfamily of multifunctional enzymes that include, amongst others, the glutathione S-transferase μ1 (GSTM1), θ1 (GSTT1) and π1 (GSTP1) classes, play an important role in the detoxification of various toxic compounds such as xenobiotics, environmental pollutants and pesticides, chemotherapeutic drugs, chemical carcinogens and products of oxidative stress (i.e. α, β-unsaturated aldehydes, quinones, epoxides, and hydroperoxides). These are important phase II detoxifying enzymes that catalyse the conjugation of reduced glutathione (GSH), and convert hydrophobic, electrophilic xenobiotic substances to hydrophilic metabolites. Furthermore, recent evidence has shown that GSTs modulate the signalling pathways of cell proliferation, cell differentiation, and apoptosis.

Since GSTs are essential for phase II enzymatic detoxification and protect against cellular oxidative stress and exogenous chemicals, and because they are involved in and modulate various signalling pathways, including the biosynthesis of leukotrienes, prostaglandins, testosterone, and progesterone, variabilities in normal GST function might play particularly vital roles in slowly developing cancers.

The GSTT1 gene, located on chromosome 22q11.23, is reportedly expressed in human erythrocytes and various other tissues including the liver. The GSTT1 enzyme is said to catalyse the detoxification of ethylene oxide and methyl bromide, as well as other halogenated metabolites.

A deletion in this gene, called a null variant allele or null genotype, results in the absence of enzyme activity. If an individual is homozygous for a GSTT1 deletion, they are thought to be at an increased risk of malignancies because of their reduced capacity to detoxify potential carcinogens.

Prostate Cancer

A 2013 systematic review and meta-analysis from Liu et al., reportedly being the first to investigate the GSTT1-null genotype and prostate cancer susceptibility particularly in Asians, found a significant association. The inclusion of 15 studies (1 677 cases and 2 431 controls) revealed a significantly increased risk of prostate cancer within the Asian population. The possession of a dual null genotype for GSTM1 and GSTT1 posed a particularly higher risk in the same population.  

In 2014, Zhou et al. determined that the GSTT1 null genotype was distinctly associated with prostate cancer risk in Caucasians, but not in the overall population (9 752 cases and 10 530 controls). The authors mentioned though that no subgroup analyses were performed in Asian, African or African American populations due to the small number of studies and limited data sets included in the meta-analysis.

A meta-analysis from Gong et al. in 2012 also found that subjects with a dual null genotype for GSTM1 and GSTT1 were at increased risk for developing prostate cancer. Data from 37 studies comprising 7 187 prostate cancer cases and 8 761 controls however, indicated no association between the single GSTT1-null genotype and prostate cancer risk. This is reportedly consistent with the result of many former meta-analyses.

Cruciferous Vegetables

Cruciferous vegetables (Brassicaceae family) contain a variety of phytochemicals (such as vitamin C, carotenoids and flavonoids), many of which are thought to play a role in cancer protection. Isothiocyanates (ITCs), the metabolites of glucosinolates (which naturally occur in cruciferous vegetables), have been shown to exert cancer-protective effects through the inhibition of phase I enzymes and the enhancement of phase II enzymes, thus blocking chemical carcinogenesis. It has also been thought to inhibit angiogenesis, induce apoptosis, inhibit pro-inflammatory reactions by repressing NFκB, and arrest cell cycle progression.  Cruciferous vegetables represent the primary source of ITC exposure in humans.

Seow et al. (1998) suggested that the expression of GSTT1 is induced by dietary ITCs found in cruciferous vegetables such as cauliflower, broccoli, watercress and other Chinese varieties such as choi sum and kai choi. The authors found a strong and statistically significant association between the dietary intake of cruciferous vegetables and the urinary excretion of total ITC in Chinese subjects: urinary excretion of ITC was significantly higher among GSTT1-positive subjects when compared to GSTT1-null subjects.

Results from a more recent systematic review and meta-analysis indicated a statistically significant inverse association between cruciferous vegetable intake and colon cancer. Broccoli particularly exhibited protective benefits against colorectal cancer (CRC) / neoplasms; this is thought to be due to the higher concentration of glucosinolates found in broccoli, exposing the individual to higher levels of ITC and therefore may provide greater anticarcinogenic benefits. Interestingly, one serving of broccoli can contain up to 60 mg of glucoraphanin, a type of glucosinolate, whereas broccoli sprouts contain about 20–100 times more glucoraphanin than a full-grown broccoli head.