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5-a reductase inhibitors, benign prostatic hyperplasia, and risk of male breast cancer.

https://arctichealth.org/en/permalink/ahliterature271757
Source
Cancer Causes Control. 2015 Sep;26(9):1289-97
Publication Type
Article
Date
Sep-2015
Author
Robinson D
Garmo H
Holmberg L
Stattin P
Source
Cancer Causes Control. 2015 Sep;26(9):1289-97
Date
Sep-2015
Language
English
Publication Type
Article
Keywords
5-alpha Reductase Inhibitors - adverse effects - therapeutic use
Adrenergic alpha-Antagonists - adverse effects - therapeutic use
Aged
Aged, 80 and over
Breast Neoplasms, Male - chemically induced - pathology
Cohort Studies
Humans
Male
Middle Aged
Prostatic Hyperplasia - drug therapy - pathology
Risk
Sweden
Abstract
5-a reductase inhibitors (5-ARI) have been suggested to increase the risk of male breast cancer. The aim of this study was to study the risk of breast cancer in men on 5-ARI, in men with benign prostatic hyperplasia (BPH) not on 5-ARI, and in men without BPH.
We performed a population-based cohort study in Sweden with data from The Prescribed Drug Register, The Patient Register, and The Cancer Register. Men on 5-ARI, men on a-blockers, or men who had undergone a transurethral resection of the prostate (TUR-P) prior to or during 2006-2008 were included as exposed to BPH and a specific treatment thereof. For each exposed man, five unexposed men were selected. Risk of breast cancer was calculated in Cox proportional hazard models.
There were 124,183 exposed men and 545,293 unexposed men, and during follow-up (median 6 years), 99 men with breast cancer were diagnosed. Compared to unexposed men, men on 5-ARI had a hazard ratio (HR) of breast cancer of 0.74 (95% confidence interval (CI) 0.27-2.03), men on a-blockers had HR 1.47 (95% CI 0.73-2.95), and men with a TUR-P had HR 1.99 (95% CI 1.05-3.75).
No increased risk of breast cancer was observed for men on 5-ARI. However, the increased risk of breast cancer among men who had undergone a TUR-P, a strong indicator of BPH, suggests that the endocrine milieu conducive to BPH is associated with male breast cancer.
Notes
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PubMed ID
26109464 View in PubMed
Less detail

-160C/A polymorphism in the E-cadherin gene promoter and risk of hereditary, familial and sporadic prostate cancer.

https://arctichealth.org/en/permalink/ahliterature17926
Source
Int J Cancer. 2004 Apr 10;109(3):348-52
Publication Type
Article
Date
Apr-10-2004
Author
Jonsson B-A
Adami H-O
Hägglund M
Bergh A
Göransson I
Stattin P
Wiklund F
Grönberg H
Author Affiliation
Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
Source
Int J Cancer. 2004 Apr 10;109(3):348-52
Date
Apr-10-2004
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Cadherins - genetics
Case-Control Studies
Comparative Study
Gene Frequency
Genetic Predisposition to Disease
Genotype
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Promoter Regions (Genetics)
Prostate
Prostatic Neoplasms - epidemiology - genetics
Research Support, Non-U.S. Gov't
Risk factors
Sweden - epidemiology
Abstract
The E-cadherin (CDH1) gene has been associated with prostate carcinogenesis. The C/A polymorphism--160 base pairs relative to the transcription start site has been shown to decrease gene transcription. We analyzed the association between this polymorphism and the risk of sporadic, familial (2 close relatives) and hereditary (3 or more close relatives) prostate cancer. We combined data from 3 population-based epidemiologic studies in Sweden encompassing altogether 1,036 prostate cancer cases and 669 controls that were genotyped for the short nucleotide polymorphism. Odds ratios with 95% confidence intervals were estimated through unconditional logistic regression. We found no significant association between the A-allele and sporadic (OR = 1.0; 95% CI = 0.8-1.2) or familial (OR = 1.4; 95% CI = 0.9-2.2) prostate cancer. In contrast, risk of hereditary cancer was increased among heterozygote CA carriers (OR = 1.7; 95% CI = 1.0-2.7) and particularly among homozygote AA carriers (OR = 2.6; 95% CI = 1.4-4.9). Our data indicate that the -160 single nucleotide polymorphism in CDH1 is a low-penetrant prostate cancer susceptibility gene that might explain a proportion of familial and notably hereditary prostate cancer.
PubMed ID
14961571 View in PubMed
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Anti-androgen prescribing patterns, patient treatment adherence and influencing factors; results from the nationwide PCBaSe Sweden.

https://arctichealth.org/en/permalink/ahliterature124635
Source
Eur J Clin Pharmacol. 2012 Dec;68(12):1619-30
Publication Type
Article
Date
Dec-2012
Author
Grundmark B
Garmo H
Zethelius B
Stattin P
Lambe M
Holmberg L
Author Affiliation
Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. birgitta.grundmark@surgsci.uu.se
Source
Eur J Clin Pharmacol. 2012 Dec;68(12):1619-30
Date
Dec-2012
Language
English
Publication Type
Article
Keywords
Aged
Androgen Antagonists - therapeutic use
Anilides - therapeutic use
Databases, Factual
Humans
Male
Medication Adherence - statistics & numerical data
Nitriles - therapeutic use
Physician's Practice Patterns - statistics & numerical data
Prostatic Neoplasms - drug therapy - epidemiology
Sweden - epidemiology
Tosyl Compounds - therapeutic use
Abstract
Adherence has not been studied in male oncology populations. The aim of this study on both the prescriber and user perspectives in prostate cancer treatment was to analyse real-life prescribing patterns of anti-androgens (AA), primarily bicalutamide, and factors influencing the patients' adherence to treatment.
A nationwide clinical cohort of incident prostate cancer, PCBaSe, was linked to the Swedish Prescribed Drug Register. Men with a planned first line monotherapy AA treatment were identified; dosages and extent of off-label treatment were investigated. Cumulative incidence proportions for reasons for drug discontinuation were calculated. Factors potentially influencing adherence were explored using the medical possession ratio based on the individual prescribed daily dose.
First line monotherapy AA was planned in 4.4 % of all incident cases and in 2.1 % of low risk disease cases. Among 1,406 men prescribed bicalutamide, 1,109 (79 %) received the approved daily dose of 150 mg. Discontinuation reasons differed with disease severity. Off-label, low-dose prescription associated with age above 75 years and disease categorised as low risk was noted in 297 men (21 %). Sixty percent of the men adhered well, i.e. to =80 %. Age above 75 years and less severe disease were both negatively associated with adherence.
Patient age and tumour risk group influenced the prescriber's choice of dose, pointing to important issues for critical reflection. Possible over-treatment was noted in low risk disease. Interventions to increase adherence in older men and in men with less severe disease are worth considering after critically reviewing the appropriateness of the treatment indication, especially in the latter case.
PubMed ID
22562608 View in PubMed
Less detail

Association between duration and type of androgen deprivation therapy and risk of diabetes in men with prostate cancer.

https://arctichealth.org/en/permalink/ahliterature282301
Source
Int J Cancer. 2016 Dec 15;139(12):2698-2704
Publication Type
Article
Date
Dec-15-2016
Author
Crawley D
Garmo H
Rudman S
Stattin P
Häggström C
Zethelius B
Holmberg L
Adolfsson J
Hemelrijck MV
Source
Int J Cancer. 2016 Dec 15;139(12):2698-2704
Date
Dec-15-2016
Language
English
Publication Type
Article
Keywords
Aged
Aged, 80 and over
Androgen Antagonists - adverse effects - therapeutic use
Antineoplastic Agents, Hormonal - adverse effects - therapeutic use
Biomarkers, Tumor
Diabetes Mellitus, Type 2 - epidemiology - etiology
Humans
Incidence
Male
Middle Aged
Neoplasm Grading
Neoplasm Staging
Orchiectomy - adverse effects
Proportional Hazards Models
Prostatic Neoplasms - complications - diagnosis - therapy
Registries
Risk
Sweden - epidemiology
Abstract
Androgen deprivation therapy (ADT) for prostate cancer (PCa) increases risk of type 2 diabetes (T2DM); however the association between types and duration of ADT has not been fully elucidated. We examined how type and duration of ADT affects risk of T2DM. Using data from Prostate Cancer database Sweden (PCBaSe) we investigated risk of T2DM in a cohort of 34,031 men with PCa on ADT; i.e., anti-androgens (AA), orchiectomy, or gonadotropin-releasing hormone (GnRH) agonists compared to an age-matched, PCa-free comparison cohort (n?=?167,205) using multivariate Cox proportional hazard regression. T2DM was defined as a newly filled prescription for metformin, sulphonylurea, or insulin in the Prescribed Drug Register. A total of 21,874 men with PCa received GnRH agonists, 9,143 AA and 3,014 underwent orchiectomy. Risk of T2DM was increased in men in the GnRH agonists/orchiectomy group during the first 3 years of ADT [i.e., 1?-?1.5 years HR: 1.61 (95%CI: 1.36?-?1.91)], compared to PCa-free men. The risk decreased thereafter (e.g., 3?-?4 years HR: 1.17 (95% CI: 0.98?-?1.40)). Conversely, no increased risk was seen in men on AA (HR: 0.74 (95%CI: 0.65?-?0.84). The incidence of T2DM per 1,000 person-years was 10 for PCa-free men, 8 for men on AA, and 13 for men on GnRH agonists/orchiectomy. Duration of ADT has a significant impact on risk of T2DM. With the peak after three years of treatment, our data indicates that men on ADT, even for a limited period of time, such as adjuvant to radiotherapy, are at increased risk of T2DM.
Notes
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PubMed ID
27557616 View in PubMed
Less detail

Risk and timing of cardiovascular disease after androgen-deprivation therapy in men with prostate cancer.

https://arctichealth.org/en/permalink/ahliterature263530
Source
J Clin Oncol. 2015 Apr 10;33(11):1243-51
Publication Type
Article
Date
Apr-10-2015
Author
O'Farrell S
Garmo H
Holmberg L
Adolfsson J
Stattin P
Van Hemelrijck M
Source
J Clin Oncol. 2015 Apr 10;33(11):1243-51
Date
Apr-10-2015
Language
English
Publication Type
Article
Keywords
Aged
Aged, 80 and over
Androgen Antagonists - adverse effects
Antineoplastic Agents, Hormonal - adverse effects
Cardiovascular Diseases - chemically induced - diagnosis - epidemiology
Case-Control Studies
Humans
Incidence
Male
Middle Aged
Multivariate Analysis
Orchiectomy - adverse effects
Patient Selection
Proportional Hazards Models
Prostatic Neoplasms - therapy
Registries
Risk assessment
Risk factors
Sweden - epidemiology
Time Factors
Treatment Outcome
Abstract
Findings on the association between risk of cardiovascular disease (CVD) and the duration and type of androgen-deprivation therapy (ADT) in men with prostate cancer (PCa) are inconsistent.
By using data on filled drug prescriptions in Swedish national health care registers, we investigated the risk of CVD in a cohort of 41,362 men with PCa on ADT compared with an age-matched, PCa-free comparison cohort (n = 187,785) by use of multivariable Cox proportional hazards regression models.
From 2006 to 2012, 10,656 men were on antiandrogens (AA), 26,959 were on gonadotropin-releasing hormone (GnRH) agonists, and 3,747 underwent surgical orchiectomy. CVD risk was increased in men on GnRH agonists compared with the comparison cohort (hazard ratio [HR] of incident CVD, 1.21; 95% CI, 1.18 to 1.25; and orchiectomy: HR, 1.16; 95% CI, 1.08 to 1.25). Men with PCa on AA were at decreased risk (HR of incident CVD, 0.87; 95% CI, 0.82 to 0.91). CVD risk was highest during the first 6 months of ADT in men who experienced two or more cardiovascular events before therapy, with an HR of CVD during the first 6 months of GnRH agonist therapy of 1.91 (95% CI, 1.66 to 2.20), an HR of CVD with AA of 1.60 (95% CI, 1.24 to 2.06), and an HR of CVD with orchiectomy of 1.79 (95% CI, 1.16 to 2.76) versus the comparison cohort.
Our results support that there should be a solid indication for ADT in men with PCa so that benefit outweighs potential harm; this is of particular importance among men with a recent history of CVD.
Notes
Comment In: J Clin Oncol. 2015 Apr 10;33(11):1232-425753444
PubMed ID
25732167 View in PubMed
Less detail