CYP1A1 is a susceptibility gene for lung cancer among non-smoking Asian women and this association can be influenced by ETS exposure and genetic variation at GST genes.
It has been suggested that polymorphisms in the GST genes are risk factors for lung cancer, but a large number of studies have reported apparently conflicting results.
It catalyzes the reduction of glutathione to its thioester; thus, deficiency in GST activity due to homozygous deletion of the GSTT1 gene (null genotype) may play a role in the induction of lung cancer by smoking.
Then, co-immunoprecipitation (Co-IP) and GST-pull down assays indicated that the candidate protein-SLC27A4 directly interacts with ATG4B in lung cancer cell lines.
The relationships between smoking and the expression of glutathione S-transferase (GST*) isozymes GSTM1-1, GSTM3-3, GSTP1-1 and GSTA1-1/2-2 (GSTA1/2), or between smoking and activities of epoxide hydrolase (EH) and aryl hydrocarbon hydroxylase (AHH) were investigated in lung samples from 27 patients with lung cancer and 11 control patients by immunoblot analysis and enzyme assays.
The results showed that the frequencies of glutathione S-transferase (GST) M1-null (GSTM1-) or GSTT1-null (GSTT1-) genotype alone, or combined form of both in lung cancer patients were significantly higher than those of the controls.
Frequent intake of quercetin-rich foods was inversely associated with lung cancer risk (OR = 0.49; 95% CI: 0.37-0.67; P-trend < 0.001) and did not differ by P450 or GST genotypes, gender or histological subtypes.
Particularly, genetic polymorphisms in NAD(P)H-quinone oxidoreductase (NQO1), cytochrome P450 (CYP)1A1, myeloperoxidase (MPO), glutathione-S-transferase (GST)P1, GSTT1, and GSTM1, and have been suspected to affect lung cancer risk.
Previous studies have suggested that GST genotypes may play a role in determining susceptibility to lung cancer, though the data are often conflicting.
GST pi was also variably expressed in human tumors, with the lowest relative levels occurring in lymphoma and breast cancer and the highest levels found in lung cancer and head and neck tumors.
The association between ITC and cancer, and its modification by GST status, is most consistent for lung cancer and appears to be strongest among current smokers.
Conjugation and elimination of ITCs is enhanced in GST-non-null relative to -null individuals, such that the GST metabolic genotype modifies the protective effect of ITCs on lung cancer development.