Glutathione S-transferase M1, T1, and P1 polymorphisms and prostate cancer risk in middle-aged men.

The Prostate

PubMedID: 16173036

Agalliu I, Langeberg WJ, Lampe JW, Salinas CA, Stanford JL. Glutathione S-transferase M1, T1, and P1 polymorphisms and prostate cancer risk in middle-aged men. Prostate. 2006;66(2):146-56.
BACKGROUND
The glutathione S-transferase (GST) enzymes detoxify several carcinogens. Genetic polymorphisms in GSTM1, T1, and P1 (Ile105Val) have been associated with prostate cancer, however, results have been inconsistent across studies.

METHODS
Data from a population-based case-control study in King County, Washington, were used to further evaluate the relationships between these GST polymorphisms and prostate cancer. Incident cases (n = 590) were 40-64 years old, diagnosed from 1993 through 1996, and identified via the SEER cancer registry. Controls (n = 538) were identified via random digit dialing, and frequency age-matched to cases. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI).

RESULTS
Risk of prostate cancer was moderately increased among Caucasians with the GSTM1-null genotype (OR = 1.54; 95% CI 1.19-2.01). There were no associations for either GSTT1 or P1(Ile105Val). The association between the GSTM1-null genotype and prostate cancer was not different according to cancer aggressiveness defined by stage at diagnosis and Gleason score. Among GSTM1-null Caucasians, the relative risk of prostate cancer increased linearly with increasing pack-years of smoking (P-value for trend = 0.007), with the highest ORs observed for smokers of >30 pack-years.

CONCLUSIONS
Findings suggest that the GSTM1-null genotype defines a subgroup of men at higher risk of prostate cancer, particularly if they are heavy smokers.