METHODS: To estimate individual susceptibility to
arsenic-induced UC, 764
DNA specimens from our long-term follow-up cohort in Southwestern Taiwan were used and the genetic polymorphisms in GSTM1, GSTT1, GSTP1 and
arsenic methylation
enzymes including GSTO1 and GSTO2 were genotyped.
RESULTS: The GSTT1 null was marginally associated with increased urothelial
carcinoma (UC) risk (HR, 1.91, 95% CI, 1.00-3.65), while the association was not observed for other
GSTs. Among the subjects with cumulative
arsenic exposure (CAE) ≥ 20 mg/L*year, the GSTT1 null genotype conferred a significantly increased
cancer risk (RR, 3.25, 95% CI, 1.20-8.80). The gene-environment interaction between the GSTT1 and high
arsenic exposure with respect to
cancer risk was statistically significant (multiplicative model, p = 0.0151) and etiologic fraction was as high as 0.86 (95% CI, 0.51-1.22). The genetic effects of GSTO1/GSTO2 were largely confined to high
arsenic level (CAE ≥ 20). Diplotype analysis showed that among subjects exposed to high levels of
arsenic, the AGG/AGG variant of GSTO1 Ala140Asp, GSTO2
5'UTR (-183)A/G, and GSTO2 Asn142Asp was associated with an increased
cancer risk (HRs, 4.91, 95% CI, 1.02-23.74) when compared to the all-wildtype reference, respectively.
CONCLUSIONS: