ATAAA repeat upstream of glutathione S-transferase P1 and prostate cancer risk

Elizabeth A. Platz, Krishna Krithivas, Philip W. Kantoff, Meir J. Stampfer, Edward Giovannucci

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives. 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.

Original languageEnglish (US)
Pages (from-to)159-164
Number of pages6
JournalUrology
Volume59
Issue number1
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Urology

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