Serum testosterone and prostate cancer in men with germline BRCA1/2 pathogenic variants

The relation of serum androgens and the development of prostate cancer (PCa) is subject of debate. Lower total testosterone (TT) levels have been associated with increased PCa detection and worse pathological features after treatment. However, data from the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) and Prostate Cancer Prevention (PCPT) trial groups indicate no association. The aim of this study is to investigate the association of serum androgen levels and PCa detection in a prospective screening study of men at higher genetic risk of aggressive PCa due to BRCA1/2 pathogenic variants (PVs), the IMPACT study.

[1]  R. Eeles,et al.  Prostate Cancer Risks for Male BRCA1 and BRCA2 Mutation Carriers: A Prospective Cohort Study☆ , 2020, European urology.

[2]  L. Kiemeney,et al.  Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers , 2019, European urology.

[3]  J. Jeter,et al.  The association of BRCA1 and BRCA2 mutations with prostate cancer risk, frequency, and mortality: A meta‐analysis , 2022 .

[4]  D. Margel,et al.  Is there a difference in testosterone levels and its regulators in men carrying BRCA mutations? , 2017, Oncotarget.

[5]  J. Wright,et al.  Stable Intraprostatic Dihydrotestosterone in Healthy Medically Castrate Men Treated With Exogenous Testosterone. , 2016, The Journal of clinical endocrinology and metabolism.

[6]  K. Knudsen,et al.  Linking DNA Damage and Hormone Signaling Pathways in Cancer , 2016, Trends in Endocrinology & Metabolism.

[7]  I. Thompson,et al.  Serum androgens and prostate cancer risk: results from the placebo arm of the Prostate Cancer Prevention Trial , 2016, Cancer Causes & Control.

[8]  Hui Hu,et al.  Current opinion on the role of testosterone in the development of prostate cancer: a dynamic model , 2015, BMC Cancer.

[9]  R. Eeles,et al.  Effect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival After Radical Treatment for Localised Prostate Cancer. , 2015, European urology.

[10]  S. Byun,et al.  Preoperative Serum Sex Hormone-Binding Globulin Level Is an Independent Predictor of Biochemical Outcome After Radical Prostatectomy , 2015, Medicine.

[11]  A. Bauman,et al.  Age-specific changes in BMI and BMI distribution among Australian adults using cross-sectional surveys from 1980 to 2008 , 2014, International Journal of Obesity.

[12]  A. Hayes,et al.  Age specific changes in BMI and BMI distribution among Australian adults using cross-sectional surveys from 1980 to 2008 , 2014 .

[13]  L. Kiemeney,et al.  Targeted Prostate Cancer Screening in BRCA1 and BRCA2 Mutation Carriers: Results from the Initial Screening Round of the IMPACT Study , 2014, European urology.

[14]  F. Feng,et al.  A hormone-DNA repair circuit governs the response to genotoxic insult. , 2013, Cancer discovery.

[15]  H. Hieronymus,et al.  Androgen receptor signaling regulates DNA repair in prostate cancers. , 2013, Cancer discovery.

[16]  H. Scher,et al.  Serum androgens as prognostic biomarkers in castration-resistant prostate cancer: results from an analysis of a randomized phase III trial. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  J. Nesland,et al.  SHBG Is an Important Factor in Stemness Induction of Cells by DHT In Vitro and Associated with Poor Clinical Features of Prostate Carcinomas , 2013, PloS one.

[18]  A. Sallent,et al.  Higher sex hormone-binding globulin and lower bioavailable testosterone are related to prostate cancer detection on prostate biopsy , 2013, Scandinavian journal of urology.

[19]  F. Migliorini,et al.  Serum Total Testosterone Is a Significant Preoperative Variable Independently Contributing to Separating the Prostate Cancer Population into Prostatectomy Gleason Score Groups , 2013, Urologia Internationalis.

[20]  R. Eeles,et al.  Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  S. Glina,et al.  Study of testosterone as a predictor of tumor aggressiveness in patients with prostate cancer. , 2013, International braz j urol : official journal of the Brazilian Society of Urology.

[22]  E. Yang,et al.  BRCA1-Ku80 Protein Interaction Enhances End-joining Fidelity of Chromosomal Double-strand Breaks in the G1 Phase of the Cell Cycle* , 2013, The Journal of Biological Chemistry.

[23]  U. Capitanio,et al.  Preoperative sex steroids are significant predictors of early biochemical recurrence after radical prostatectomy , 2013, World Journal of Urology.

[24]  X. Yao,et al.  Low pretreatment serum total testosterone is associated with a high incidence of Gleason score 8–10 disease in prostatectomy specimens: data from ethnic Chinese patients with localized prostate cancer , 2012, BJU international.

[25]  G. Andriole,et al.  Serum testosterone and dihydrotestosterone and prostate cancer risk in the placebo arm of the Reduction by Dutasteride of Prostate Cancer Events trial. , 2012, European urology.

[26]  R. Eeles,et al.  The role of BRCA1 and BRCA2 in prostate cancer. , 2012, Asian journal of andrology.

[27]  D. Easton,et al.  BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients , 2011, British Journal of Cancer.

[28]  A. Araujo,et al.  The effect of diurnal variation on clinical measurement of serum testosterone and other sex hormone levels in men. , 2009, The Journal of clinical endocrinology and metabolism.

[29]  A. Traish,et al.  Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. , 2009, European urology.

[30]  J. Kaufman,et al.  Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. , 2009, European urology.

[31]  I. Thompson,et al.  Investigation, treatment and monitoring of late-onset hypogonadism in males , 2008, European journal of endocrinology.

[32]  P Ghadirian,et al.  Rapid progression of prostate cancer in men with a BRCA2 mutation , 2008, British Journal of Cancer.

[33]  J. Mckinlay,et al.  Intraindividual variation in levels of serum testosterone and other reproductive and adrenal hormones in men , 2007, Clinical endocrinology.

[34]  A. Morgentaler.  Testosterone replacement therapy and prostate cancer. , 2007, The Urologic clinics of North America.

[35]  Y. Ishikawa,et al.  Preoperative serum testosterone level as an independent predictor of treatment failure following radical prostatectomy. , 2007, European urology.

[36]  R. Eeles,et al.  A review of targeted screening for prostate cancer: introducing the IMPACT Study , 2007, BJU international.

[37]  A. Ashworth,et al.  The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability , 2006, Oncogene.

[38]  R. Gómez-Pérez,et al.  RELATIONSHIP BETWEEN BMI, TOTAL TESTOSTERONE, SEX HORMONE-BINDING-GLOBULIN, LEPTIN, INSULIN AND INSULIN RESISTANCE IN OBESE MEN , 2006, Archives of andrology.

[39]  M. Kattan,et al.  Testosterone as a predictor of pathological stage in clinically localized prostate cancer. , 2005, The Journal of urology.

[40]  I. Verma,et al.  BRCA2 cooperates with histone acetyltransferases in androgen receptor-mediated transcription , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[41]  Ashok R Venkitaraman,et al.  Cancer Susceptibility and the Functions of BRCA1 and BRCA2 , 2002, Cell.

[42]  R. Dahiya,et al.  DNA mismatch repair enzyme activity and gene expression in prostate cancer. , 2001, Biochemical and biophysical research communications.

[43]  W. DeWolf,et al.  Is low serum free testosterone a marker for high grade prostate cancer? , 2000, The Journal of urology.

[44]  A. Vermeulen,et al.  A critical evaluation of simple methods for the estimation of free testosterone in serum. , 1999, The Journal of clinical endocrinology and metabolism.

[45]  H. Olsson.  Cancer risks in BRCA2 mutation carriers. , 1999, Journal of the National Cancer Institute.

[46]  C. Huggins,et al.  Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate , 1941, CA: a cancer journal for clinicians.