Dataset Information

Inherited variations in AR, ESR1, and ESR2 genes are not associated with prostate cancer aggressiveness or with efficacy of androgen deprivation therapy.

ABSTRACT: Sex steroid hormone receptors mediate essential processes in normal prostate growth and contribute to prostate cancer development.In this study, we investigated the association between common inherited variation of the AR, ESR1, and ESR2 genes and two clinically relevant traits: the risk of developing aggressive prostate cancer and the response to androgen deprivation therapy (ADT) in a hospital-based cohort. A total of 43 tagging single nucleotide polymorphisms covering the loci of AR (n = 4), ESR1 (n = 32), and ESR2 (n = 7) were successfully genotyped in 4,073 prostate cancer cases.None of these single nucleotide polymorphisms were significantly associated with disease aggressiveness as assessed by the D'Amico risk classification, pathologic stage, or the response to ADT.Our results suggest that common genetic variations in AR, ESR1, or ESR2 are not strongly associated with prostate cancer aggressiveness or response to ADT.Our study did not find convincing evidence of inherited variations in the major receptors for androgens and estrogens and their associations with prostate cancer traits.

SUBMITTER: Sun T

PROVIDER: S-EPMC3755451 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Inherited variations in AR, ESR1, and ESR2 genes are not associated with prostate cancer aggressiveness or with efficacy of androgen deprivation therapy.

Sun Tong T Lee Gwo-Shu Mary GS Werner Lillian L Pomerantz Mark M Oh William K WK Kantoff Philip W PW Freedman Matthew L ML

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20100701 7

<h4>Background</h4>Sex steroid hormone receptors mediate essential processes in normal prostate growth and contribute to prostate cancer development.<h4>Method</h4>In this study, we investigated the association between common inherited variation of the AR, ESR1, and ESR2 genes and two clinically relevant traits: the risk of developing aggressive prostate cancer and the response to androgen deprivation therapy (ADT) in a hospital-based cohort. A total of 43 tagging single nucleotide polymorphisms ...[more]

PMID: 20615892

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Project description:BackgroundCastration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving androgen-deprivation therapy. Replacing androgens before progression of the disease is hypothesized to prolong androgen dependence.MethodsMen with newly diagnosed, metastatic, hormone-sensitive prostate cancer, a performance status of 0 to 2, and a prostate-specific antigen (PSA) level of 5 ng per milliliter or higher received a luteinizing hormone-releasing hormone analogue and an antiandrogen agent for 7 months. We then randomly assigned patients in whom the PSA level fell to 4 ng per milliliter or lower to continuous or intermittent androgen deprivation, with patients stratified according to prior or no prior hormonal therapy, performance status, and extent of disease (minimal or extensive). The coprimary objectives were to assess whether intermittent therapy was noninferior to continuous therapy with respect to survival, with a one-sided test with an upper boundary of the hazard ratio of 1.20, and whether quality of life differed between the groups 3 months after randomization.ResultsA total of 3040 patients were enrolled, of whom 1535 were included in the analysis: 765 randomly assigned to continuous androgen deprivation and 770 assigned to intermittent androgen deprivation. The median follow-up period was 9.8 years. Median survival was 5.8 years in the continuous-therapy group and 5.1 years in the intermittent-therapy group (hazard ratio for death with intermittent therapy, 1.10; 90% confidence interval, 0.99 to 1.23). Intermittent therapy was associated with better erectile function and mental health (P<0.001 and P=0.003, respectively) at month 3 but not thereafter. There were no significant differences between the groups in the number of treatment-related high-grade adverse events.ConclusionsOur findings were statistically inconclusive. In patients with metastatic hormone-sensitive prostate cancer, the confidence interval for survival exceeded the upper boundary for noninferiority, suggesting that we cannot rule out a 20% greater risk of death with intermittent therapy than with continuous therapy, but too few events occurred to rule out significant inferiority of intermittent therapy. Intermittent therapy resulted in small improvements in quality of life. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00002651.).

Dataset Information

Inherited variations in AR, ESR1, and ESR2 genes are not associated with prostate cancer aggressiveness or with efficacy of androgen deprivation therapy.

Publications

Inherited variations in AR, ESR1, and ESR2 genes are not associated with prostate cancer aggressiveness or with efficacy of androgen deprivation therapy.

Similar Datasets

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