Among the six genes, 6 methylation sites in ARHGDIB, 3 in GSTM2, 1 in ARL14, 2 in LINC00526 and 2 in LURAP1 were meaningfully associated with BC prognosis.
The glutathione S-transferase M1-null genotype also enhanced the risk of bladder cancer among subjects exposed to solvents (OR = 6,5, 95% CI = 2.1-19.7, p = 0.001).
However, the most significant effect on bladder cancer risk was observed in smokers carrying lower activity GSTA1-AB/BB and GSTM-null genotype (OR = 3.5, P < 0.05) compared with GSTA1-AA and GSTM1-active non-smokers.
The main RF were a) age and gender (diagnosed at age 65 and over, with a 4:1 ratio of males to females); b) race, ethnicity and geographic location (predominantly in Caucasians and in Southern European countries); c) genetic (N-acetyltransferase-2 and glutathione s-transferase M1 gene mutations, which significantly increase the risk for BC); d) occupational, which represent 5%-10% of BC RF; and f) occupations with high BC risk, such as aluminium production, the manufacture of dyes, paints and colourings, the rubber industry and the extraction and industrial use of fossil fuels.
Numerous studies have shown that glutathione S-transferase M1 deficiency (GSTM1*0/0) increases the risk for lung and bladder cancer but the overall risk attributable to GSTM1*0/0 was only around 1.3 according to meta-analyses.
Multiple studies in the general population have suggested that subjects with the glutathione S-transferase M1 (GSTM1)-null genotype, who lack functional GSTM1, are at higher risk for bladder cancer.