Recent molecular epidemiology has indicated that activation of brominated trihalomethanes by the enzyme GSTT1 and the lack of metabolism of haloacetic acids by a variant of enzyme GSTZ1 are likely causative mechanisms for bladder cancer associated with exposure to chlorinated water.
Bladder cancer risk overall was associated with GSTO2 Asn142Asp (homozygous; OR=1.4; 95% CI: 1.0-1.9; P for trend=0.06) and GSTZ1Glu32Lys (homozygous; OR=1.3; 95% CI: 0.9-1.8; P for trend=0.06).
Associations between THMs and bladder cancer were stronger among subjects who were GSTT1 +/+ or +/- versus GSTT1 null (P(interaction) = 0.021), GSTZ1rs1046428 CT/TT versus CC (P(interaction) = 0.018), or CYP2E1 rs2031920 CC versus CT/TT (P(interaction) = 0.035).