Polymorphisms in glutathione S-transferase genes increase risk of prostate cancer biochemical recurrence differentially by ethnicity and disease severity.
OBJECTIVE
Genetic polymorphisms that modify the detoxifying activity of glutathione S-transferases (GSTs) can affect the level of carcinogenic metabolites created by endogenous steroid hormones and exogenous chemical substances. Although the GSTM1 null genotype has been shown to increase prostate cancer mortality in Caucasians, potential associations between GST polymorphisms and prostate cancer biochemical recurrence (BCR) have not been well studied, particularly in African-Americans.


METHODS
We examined potential associations between the GSTM1 null, GSTT1 null and GSTP1 Ile105Val polymorphisms and BCR, after prostatectomy, in 168 African-American and 226 Caucasian patients treated at Henry Ford Hospital in Detroit, Michigan using Cox proportional hazards modeling.


RESULTS
We found that African-Americans with the GSTT1 null genotype had increased BCR risk compared to those having GSTT1 present (hazard ratio (HR) = 2.30; 95% CI = 1.01–5.18; p = 0.04); and African-Americans with the GSTT1 null genotype and high grade tumors had an even greater risk (HR = 7.82; 95% CI = 2.49–24.50; p < 0.001). In Caucasians, an increased risk was observed in those patients with high grade tumors and the GSTM1 null genotype (HR = 2.88; 95% CI = 1.16–7.14; p = 0.02). Similar associations were observed for advanced stage and more aggressive (high grade or advanced stage) disease.


CONCLUSIONS
Our results suggest GSTs may hold promise as therapeutic targets in more advanced prostate cancers, particularly, in African-Americans.
Nock
Nora L
NL
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA. nln@case.edu
Bock
Cathryn
C
Neslund-Dudas
Christine
C
Beebe-Dimmer
Jennifer
J
Rundle
Andrew
A
Tang
Deliang
D
Jankowski
Michelle
M
Rybicki
Benjamin A
BA
D001741:Black or African American / Q000235:genetics; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood*; D002277:Carcinoma / Q000097:blood / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D051549:Glutathione S-Transferase pi / Q000235:genetics / Q000502:physiology; D005982:Glutathione Transferase / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic / Q000502:physiology; D011471:Prostatic Neoplasms / Q000097:blood / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D012008:Recurrence; D012307:Risk Factors; D012720:Severity of Illness Index
D014408:Biomarkers, Tumor; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human