Glutathione S-transferase M1, T1, and P1 polymorphisms and prostate cancer risk in middle-aged men.
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.
Agalliu
Ilir
I
Epidemiology Program, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Langeberg
Wendy J
WJ
Lampe
Johanna W
JW
Salinas
Claudia A
CA
Stanford
Janet L
JL
D000328:Adult; D000367:Age Factors; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000235:genetics; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics* / Q000502:physiology; D005982:Glutathione Transferase / Q000235:genetics* / Q000502:physiology; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking; D044465:White People / Q000235:genetics
D004273:DNA, Neoplasm; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human