Sex Steroid Hormones and the Androgen Receptor Gene CAG Repeat and Subsequent Risk of Prostate Cancer in the Prostate-Specific Antigen Era

Platz, Elizabeth A.; Leitzmann, Michael F.; Rifai, Nader; Kantoff, Philip W.; Chen, Yen‐Ching; Stampfer, Meir J.; Willett, Walter C.; Giovannucci, Edward

doi:10.1158/1055-9965.epi-04-0371

Cited by 214 publications

(187 citation statements)

References 31 publications

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“…17 Moreover, in multiple studies higher insulin levels among men with prostate cancer have been linked with prostate cancer death. 18,19 In addition, obese men have lower androgen levels, which may promote more aggressive cancers, 20 though this remains a controversial hypothesis. Moreover, obesity is associated with a highcalorie, high-fat, high-refined carbohydrate diet, which may promote prostate cancer growth.…”

Section: Discussionmentioning

confidence: 99%

Obese men have higher-grade and larger tumors: an analysis of the duke prostate center database

Freedland

Bañez

Sun

et al. 2009

Prostate Cancer Prostatic Dis

126

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Obesity is associated with increased risk of positive surgical margins and prostate specific antigen (PSA) recurrence among men undergoing radical prostatectomy. To what degree positive margins contribute to poorer outcome is unclear. Thus, we sought to examine the association between body mass index (BMI) and more objective measures of tumor aggressiveness, tumor grade and size. We carried out a retrospective analysis of 2302 patients treated with radical prostatectomy at the Duke Prostate Center from 1988-2007. Tumor volume was calculated by multiplying prostate weight by percent of specimen involved with cancer. Associations between BMI and tumor volume and highgrade disease (GleasonX4 þ 3) independent of pre-operative clinical characteristics of age, race, PSA, clinical stage, biopsy Gleason sum, and year of surgery were assessed using linear and logistic regression, respectively. Mean and median BMI among all subjects was 28.1 and 27.6 kg m -2 , respectively. Increased BMI was significantly associated with younger age (Po0.001), black race (Po0.001), more recent year of surgery (Po0.001), and positive surgical margins (Po0.001). After adjusting for multiple clinical pre-operative characteristics, higher BMI was associated with a greater percent of the prostate involved with cancer (P ¼ 0.003), increased tumor volume (Po0.001), and high-grade disease (P ¼ 0.007). Men with a BMI X35 kg m 2 had nearly 40% larger mean tumor volumes than normal weight men (5.1 versus 3.7 cc), after adjustment for multiple clinical characteristics. In this study, obese men undergoing radical prostatectomy had higher-grade and larger tumors, providing further evidence that obese men undergoing radical prostatectomy have more aggressive prostate cancers.

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Section: Discussionmentioning

confidence: 99%

Obese men have higher-grade and larger tumors: an analysis of the duke prostate center database

Freedland

Bañez

Sun

et al. 2009

Prostate Cancer Prostatic Dis

126

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“…high grade tumors. 21,22 A limitation in comparing studies is that age-specific associations were often not reported, 12,16,20,24,25,27 and age distributions and analytic age strata have differed between investigations. Also, PSA, and associated likelihood of cancer detection, may be correlated with serum androgens, 21 however, in our study testosterone and PSA levels were unrelated in either cases or controls.…”

Section: Discussionmentioning

confidence: 99%

“…36 Final models included mutual adjustment for androgens and SHBG. 21,37,38 To determine if the relationship between the measured analytes and prostate cancer risk differed by these factors, stratification was performed by age (<65 vs. 651 years), BMI (<25, 25-30 and 30 kg/m 2 ) and time between blood draw and diagnosis (1-2 vs. 3-7 years). Likelihood ratio tests were performed to test for multiplicative interactions.…”

Section: Statistical Analysesmentioning

confidence: 99%

“…[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] We conducted a large nested case-control study including 727 cases and 889 controls, using prediagnostic serum samples, in the prospective Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, to examine associations between D4-A, T, SHBG, and 3a-diolG and risk of prostate cancer.…”

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confidence: 99%

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Endogenous sex hormones and the risk of prostate cancer: A prospective study

Weiss¹,

Huang²,

Rinaldi

et al. 2008

Intl Journal of Cancer

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Sex steroid hormones influence prostate development and maintenance through their roles in prostate cellular proliferation, differentiation and apoptosis. Although suspected to be involved in prostate carcinogenesis, an association between circulating androgens and prostate cancer has not been clearly established in epidemiologic studies. We conducted a nested case-control study with prospectively collected samples in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, to examine associations of prostate cancer with androstenedione (D4-A), testosterone (T), sex hormone-binding globulin (SHBG) and 3a-androstanediol glucuronide (3a-diolG). A total of 727 incident Caucasian prostate cancer cases (age ≥ 65 years, N 5 396) and 889 matched controls were selected for this analysis. Overall, prostate cancer risks were unrelated to serum T, estimated free and bioavailable T, and SHBG; however, risks increased with increasing T:SHBG ratio (p trend 5 0.01), mostly related to risk in older men (≥65 years, p trend 5 0.001), particularly for aggressive disease [highest versus lowest quartile: odds ratio (OR) 2.76, 95% confidence interval (CI) 1. 50-5.09]. No clear patterns were noted for D4-A and 3a-diolG. In summary, our large prospective study did not show convincing evidence of a relationship between serum sex hormones and prostate cancer. T:SHBG ratio was related to risk in this older population of men, but the significance of this ratio in steroidal biology is unclear. ' 2008 Wiley-Liss, Inc.Key words: prostate; hormones; testosterone; 3a-diolG; sex hormonebinding globulin; androstenedione Prostate cancer is the most commonly diagnosed nonskin cancer and the second leading cause of cancer mortality among men in the United States. 1 Age, race and family history of prostate cancer are the only well-established risk factors for this disease (reviewed in Refs. 2, 3). Androgens are important in prostate cancer; prolonged administration of testosterone induces prostate cancer in animal models 4,5 and androgens are important modifiers of disease progression and metastases. 6,7 Testosterone (T) is derived in the testes from androstenedione (D4-A) and is converted in the prostate to its more active form, dihydrotestosterone (DHT). 8 DHT binds in a complex to the androgen receptor (AR), influencing cellular proliferation through control of numerous gene-regulating AR response elements. DHT is further metabolized to 3a-androstanediol (3a-diol) and 3a-androstanediol glucuronide (3a-diolG). In circulation, sex hormone-binding globulin (SHBG) is the major high-affinity carrier of T, while serum albumin serves as an androgen carrier of low binding affinity. 8 SHBG may also play a role directly in steroid signaling, through binding to a receptor (R SHBG ), inducing cAMP synthesis (reviewed in Ref. 9).Although androgens are important in prostate carcinogenesis, 10 epidemiologic studies relating serum hormone levels to prostate cancer risk have been inconclusive, with most prospective studies in the United States an...

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“…However, there are negative reports for relations with the number of CAG repeat and reactivity of carcinogenesis and hormonal therapy [9,10].…”

Section: Expression and Activation Of Androgen Receptor (Ar) In Prostmentioning

confidence: 99%

Primary combined androgen blockade in localized disease and its mechanism

Namiki¹,

Kitagawa²,

Mizokami³

et al. 2008

Best Practice & Research Clinical Endocrinology & Metab

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In spite of clinical practice guidelines such as NCI-PDQ in which primary androgen deprivation therapy (PADT) is not recommended as the primary treatment for localized prostate cancer, many patients have been treated with PADT. One of the reasons is that urologists themselves permit patients' desire because they knew the effectiveness of PADT for some patients in their experiences.In this review we demonstrated basic mechanisms and clinical efficacy of primary combined androgen blockade (PCAB) for localized or locally advanced prostate cancer.

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Sex Steroid Hormones and the Androgen Receptor Gene CAG Repeat and Subsequent Risk of Prostate Cancer in the Prostate-Specific Antigen Era

Cited by 214 publications

References 31 publications

Obese men have higher-grade and larger tumors: an analysis of the duke prostate center database

Obese men have higher-grade and larger tumors: an analysis of the duke prostate center database

Endogenous sex hormones and the risk of prostate cancer: A prospective study

Primary combined androgen blockade in localized disease and its mechanism

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