ATAAA repeat upstream of glutathione S-transferase P1 and prostate cancer risk.
OBJECTIVE
Expression of glutathione S-transferase pi (GSTP1), a detoxification enzyme that also binds steroid hormones, is diminished or absent in human prostate tumors possibly because of promoter hypermethylation. Upstream of its promoter is a polymorphic ATAAA repeat of unknown functional significance. We evaluated whether this polymorphism is associated with prostate cancer.


METHODS
Incident prostate cancer cases (n = 186) and controls (n = 398) were identified among participants in the Physicians' Health Study. DNA was extracted from peripheral whole blood, and the region encompassing the repeat was amplified using fluorescent-labeled primers. The fragments were run on polyacrylamide gels and sized by Genescan software. Alleles were designated by polymerase chain reaction fragment size. We estimated the relative risk of prostate cancer for the GSTP1 gene ATAAA alleles and genotype from logistic regression models controlling for age and cigarette smoking status.


RESULTS
Fifteen GSTP1 ATAAA alleles were observed; C (19 repeats), G (21 repeats), and I (22 repeats) accounted for 80% among the controls. Compared with C, the relative risks for prostate cancer were 1.1 (95% confidence interval 0.7 to 1.7) for G and 0.8 (95% confidence interval 0.6 to 1.2) for I. The relative risks were also not statistically significantly elevated for the less common alleles. Compared with CC, the most common genotype, none of the other genotypes appeared to be associated with an increased risk of prostate cancer.


CONCLUSIONS
The results of this study do not support an important role of the ATAAA repeat polymorphism upstream from the GSTP1 promoter in prostate cancer incidence.
Platz
Elizabeth A
EA
Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.
Krithivas
Krishna
K
Kantoff
Philip W
PW
Stampfer
Meir J
MJ
Giovannucci
Edward
E
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D016001:Confidence Intervals; D005819:Genetic Markers; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000235:genetics*; D012306:Risk
D005819:Genetic Markers; D007527:Isoenzymes; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase