A GENETIC POLYMORPHISM OF THE OSTEOPROTEGERIN GENE IS ASSOCIATED WITH AN INCREASED RISK OF ADVANCED PROSTATE CANCER

2009 ◽  
Vol 181 (4S) ◽  
pp. 168-168
Author(s):  
Naofumi Narita ◽  
Takeshi Yuasa ◽  
Norihiko Tsuchiya ◽  
Teruaki Kumazawa ◽  
Shintaro Narita ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Genetic Polymorphism ◽  
Advanced Prostate Cancer ◽  
Increased Risk ◽  
Osteoprotegerin Gene

scholarly journals A genetic polymorphism of the osteoprotegerin gene is associated with an increased risk of advanced prostate cancer

BMC Cancer ◽  
2008 ◽  
Vol 8 (1) ◽  
Author(s):  
Naofumi Narita ◽  
Takeshi Yuasa ◽  
Norihiko Tsuchiya ◽  
Teruaki Kumazawa ◽  
Shintaro Narita ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Genetic Polymorphism ◽  
Advanced Prostate Cancer ◽  
Increased Risk ◽  
Osteoprotegerin Gene

Prostate Cancer

2018 ◽  
Author(s):  
Kathryn M. Wilson ◽  
Lorelei Mucci
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Family History ◽  
Prostate Specific Antigen ◽  
Advanced Prostate Cancer ◽  
Advanced Disease ◽  
African Ancestry ◽  
Specific Antigen ◽  
Dietary Factors ◽  
Increased Risk

Prostate cancer is among the most commonly diagnosed cancers among men, ranking second in cancer globally and first in Western countries. There are marked variations in incidence globally, and its incidence must be interpreted in the context of diagnostic intensity and screening. The uptake of prostate-specific antigen screening since the 1990s has led to dramatic increases in incidence in many countries, resulting in an increased proportion of indolent cancers that would never have come to light clinically in the absence of screening. Risk factors differ when studying prostate cancer overall versus advanced disease. Older age, African ancestry, and family history are established risk factors for prostate cancer. Obesity and smoking are not associated with risk overall, but are associated with increased risk of advanced prostate cancer. Several additional lifestyle factors, medications, and dietary factors are now emerging as risk factors for advanced disease.

Increased risk of advanced prostate cancer associated with MnSOD Ala-9-Val gene polymorphism

2011 ◽  
Vol 39 (1) ◽  
pp. 193-198 ◽  
Author(s):  
Canan Kucukgergin ◽  
Oner Sanli ◽  
Tzevat Tefik ◽  
Makbule Aydın ◽  
Faruk Ozcan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gene Polymorphism ◽  
Advanced Prostate Cancer ◽  
Increased Risk

scholarly journals trans-Fatty acid intake and increased risk of advanced prostate cancer: modification by RNASEL R462Q variant

2007 ◽  
Vol 28 (6) ◽  
pp. 1232-1236 ◽  
Author(s):  
X. Liu ◽  
F. R. Schumacher ◽  
S. J. Plummer ◽  
E. Jorgenson ◽  
G. Casey ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Trans Fatty Acid ◽  
Advanced Prostate Cancer ◽  
Fatty Acid Intake ◽  
Acid Intake ◽  
Trans Fatty Acid Intake ◽  
Increased Risk

scholarly journals The modern role of androgen deprivation therapy in the management of localised and locally advanced prostate cancer

2016 ◽  
Vol 9 (2_suppl) ◽  
pp. 24-29 ◽  
Author(s):  
Charlotte Gunner ◽  
Aziz Gulamhusein ◽  
Derek J Rosario
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Advanced Prostate Cancer ◽  
Locally Advanced ◽  
Androgen Deprivation ◽  
Locally Advanced Prostate Cancer ◽  
Curative Intent ◽  
Cardiovascular Morbidity And Mortality ◽  
Increased Risk

Introduction: Approximately 50% of men diagnosed with prostate cancer will be exposed to androgen deprivation therapy (ADT) at some stage. The role of ADT in the management of metastatic disease has long been recognised, and its place in the management of localised and locally advanced disease has become clearer in the past few years. Nevertheless, concerns remain that some men might not benefit from ADT in earlier-stage disease. The purpose of the current article is to provide a brief narrative review of the role of ADT as part of a strategy of treatment with curative intent, concentrating mainly on key recent developments in the area. Methods: Narrative literature review of key publications in the English language relating to ADT in the management of localised and locally advanced prostate cancer. Results: In locally advanced and high-risk localised prostate cancer, the use of ADT in combination with radiotherapy improves disease-specific and overall survival. There is no evidence to support the use of ADT in the treatment of low-risk localised prostate cancer. There appears to be an increased risk of cardiovascular morbidity and mortality associated with luteinizing hormone-releasing hormone agonists, particularly in men with pre-existing cardiovascular disease, but the relevance of this in the adjuvant/neoadjuvant setting is currently unclear. Conclusions: Future studies should focus on identification of men who are at risk from cardiovascular complications associated with ADT and on the comparison of radiotherapy with ADT versus surgery in the management of localised and locally advanced prostate cancer, particularly with regards to men with pre-existing comorbidities.

Circadian dysrhythm and advanced prostate cancer.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 199-199
Author(s):  
Lorelei A. Mucci ◽  
Sarah Markt ◽  
Lara Sigurdardottir ◽  
Steven W. Lockley ◽  
Katja Fall ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Circadian Rhythm ◽  
Advanced Prostate Cancer ◽  
Clock Genes ◽  
Sleep Problems ◽  
P Value ◽  
Relative Risks ◽  
Increased Risk ◽  
Falling Asleep

199 Background: The circadian rhythm regulates diverse biologic pathways including tumor oncogenes, metabolism, and cell proliferation. Dysregulation of the circadian rhythm arises from faulty input signals such as exposure to light at night, variability in core circadian rhythm genes, and variation in outputs that regulate circadian behavior including melatonin. There is compelling biologic rationale, but little human data, on circadian dysrhythm and advanced prostate cancer. Methods: We undertook an integrative molecular epidemiology study of circadian dysrhythm and advanced prostate cancer among men in the Icelandic AGES-Reykjavik cohort and the U.S. Health Professionals Follow-up Study, which allowed integration of questionnaire data, biorepositories, and long-term follow-up. We characterized circadian dysrhythm using complimentary approaches: information on sleep problems from questionnaires, prediagnostic melatonin (6-sulfatoxymelatonin) measured on first morning void urine samples, and genetic variation across twelve circadian clock genes. We used multivariable regression models to estimate relative risks (RR) and 95% confidence intervals (CI) of associations with advanced prostate cancer, adjusted for potential confounders. Results: Twenty percent of men reported sleep problems. Men who had trouble falling asleep (RR = 2.1; 95% CI 0.7-6.2) and staying asleep (RR=3.2, 95% CI 1.1-9.7) had an increased risk of developing advanced prostate cancer. Men with sleep problems had significantly lower melatonin levels compared to those without. Low melatonin levels were associated with a statistically significant 4-fold higher risk of advanced prostate cancer compared to those with high levels (95% CI: 1.25-10.0). Variant alleles in two SNPs in cryptochrome (CRY1), involved in generating and maintaining circadian rhythms, were significantly associated with risk of advanced prostate cancer in both cohorts, with a gene-level p-value<0.01. Conclusions: Our results suggest there are multiple nodes in the circadian rhythm that are associated with an increased risk of advanced prostate cancer. As such, there is the potential for complimentary strategies to target circadian disruption and reduce the risk of advanced prostate cancer.

scholarly journals Mendelian randomization does not support serum calcium in prostate cancer risk

2018 ◽  
Author(s):  
James Yarmolinsky ◽  
Katie Berryman ◽  
Ryan Langdon ◽  
Carolina Bonilla ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Causal Inference ◽  
Serum Calcium ◽  
Observational Studies ◽  
Advanced Prostate Cancer ◽  
Mendelian Randomization ◽  
Prostate Cancer Risk ◽  
A Genome ◽  
Increased Risk

AbstractBackground: Observational studies suggest that dietary and serum calcium are risk factors for prostate cancer. However, such studies suffer from residual confounding (due to unmeasured or imprecisely measured confounders), undermining causal inference. Mendelian randomization uses randomly assigned (hence unconfounded and pre-disease onset) germline genetic variation to proxy for phenotypes and strengthen causal inference in observational studies.Objective: We tested the hypothesis that serum calcium is associated with an increased risk of overall and advanced prostate cancer.Design: A genetic instrument was constructed using 5 single nucleotide polymorphisms robustly associated with serum calcium in a genome-wide association study (N ≤ 61,079). This instrument was then used to test the effect of a 0.5 mg/dL increase (1 standard deviation, SD) in serum calcium on risk of prostate cancer in 72,729 men in the PRACTICAL (Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome) Consortium (44,825 cases, 27,904 controls) and risk of advanced prostate cancer in 33,498 men (6,263 cases, 27,235 controls).Results: We found weak evidence for a protective effect of serum calcium on prostate cancer risk (odds ratio [OR] per 0.5 mg/dL increase in calcium: 0.83, 95% CI: 0.63-1.08; P=0.12). We did not find strong evidence for an effect of serum calcium on advanced prostate cancer (OR per 0.5 mg/dL increase in calcium: 0.98, 95% CI: 0.57-1.70; P=0.93).Conclusions: Our Mendelian randomization analysis does not support the hypothesis that serum calcium increases risk of overall or advanced prostate cancer.

Serum IGF-1 levels in men with advanced prostate cancer treated with the ERα agonist, GTx-758.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 171-171
Author(s):  
Evan Y. Yu ◽  
Marc Gittelman ◽  
Thomas E. Keane ◽  
Ronald Tutrone ◽  
Laurence Belkoff ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Advanced Prostate Cancer ◽  
Active Form ◽  
Total Testosterone ◽  
Reference Laboratory ◽  
Insulin Metabolism ◽  
Increased Risk ◽  
Venous Thromboembolic Events

171 Background: The insulin pathway and, in particular, insulin-like growth factor-1 (IGF-1), has been implicated in the development of prostate cancer, and serum IGF-1 levels have been associated with advanced disease. GTx-758, an ERα agonist that is being evaluated for the treatment of advanced prostate cancer, reduces serum total testosterone (T) and free T and increases SHBG. Herein, we compare the effects of GTx-758 and leuprolide on serum IGF-1 levels in men with advanced prostate cancer treated with ADT. Methods: In a Phase II study (G200705), men with advanced prostate cancer (n=159) received 1000 mg or 2000 mg of GTx-758 daily or leuprolide. Serum samples were collected from all of the men in the study and serum IGF-1 levels (ng/ml) were analyzed by a reference laboratory. All p values describe the comparison of GTx-758 treatment groups to the leuprolide treated men. Results: Through day 90, in men receiving the 1000 mg and 2000 mg doses of GTx-758 , serum IGF-1 levels were decreased by more than 70 ng/ml (greater than 50%), while levels stayed constant or increased slightly in men on leuprolide (p<0.001). As a result of an increased risk of venous thromboembolic events (VTEs) at these higher doses of GTx-758, the trial was stopped prior to its completion, and not all of the men in the study reached the 90 day treatment date (92 men reached that date). Conclusions: In men with advanced prostate cancer, the ERα agonist, GTx-758, can decrease the active form of testosterone, serum free T, to significantly lower levels than leuprolide. Patients receiving GTx-758 experienced a significant decrease in serum IGF-1. Since changes in insulin metabolism are involved in regulating prostate cancer as well as bone and systemic metabolism, the observed decreases in IGF-1 could be significant. A Phase II clinical trial utilizing lower doses of GTx-758 (G200712) is currently ongoing to determine if similar effects can be observed with a lower rate of VTEs. Clinical trial information: NCT01326312.

Rate of hot flashes in patients with advanced prostate cancer treated with GTx-758.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 129-129
Author(s):  
Evan Y. Yu ◽  
Marc Gittelman ◽  
Thomas E. Keane ◽  
Ronald Tutrone ◽  
Laurence Belkoff ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Advanced Prostate Cancer ◽  
Hot Flashes ◽  
Lower Percentage ◽  
Total Testosterone ◽  
Treatment Groups ◽  
Increased Risk ◽  
Venous Thromboembolic Events

129 Background: When androgen deprivation therapy (ADT) for prostate cancer was first developed, life expectancy for men with advanced disease was short and the systemic effects were of limited relevance. GTx-758 is a selective ERα agonist that effects serum total testosterone (T), free T, SHBG and PSA. Herein we compare the effects of GTx-758 and leuprolide on hot flashes, one of the common side effects in men on ADT. Methods: In a Phase II study (G200705), men with advanced prostate cancer (n=159) received 1000 mg or 2000 mg of GTx-758 daily or leuprolide. Utilizing a standardized instrument to measure the frequency and severity of hot flashes, data was compiled at baseline, day 28 and day 90. The number of men experiencing hot flashes were those reporting any in the period between the respective time point and the prior patient visit. All p values describe the comparison of both GTx-758 treatment groups to the leuprolide treated men. Results: At the baseline, there were no significant differences in the number of men reporting hot flashes in any of the treatment groups (p=0.065). The percentage of men who experienced a hot flash while receiving leuprolide increased significantly to 60.4% (p<0.0001) by Day 28 and increased further to 80.9% (p<0.0001) by Day 90. Although some subjects experienced hot flashes while receiving GTx-758, these men were a significantly lower percentage, 18.8 and 5.6% at the 1000 mg and 2000 mg doses of GTx-758 respectively at day 90. As a result of an increased risk of venous thromboembolic events (VTEs) at these higher doses of GTx-758, the trial was stopped prior to its completion and not all of the men on the study reached the 90 day treatment date (99 evaluable). Conclusions: Men with advanced prostate cancer, receiving GTx-758 experienced a greater than 4-fold reduction in their reported hot flashes at day 90. Since hot flashes are a major side effect that impacts the quality of life in men on ADT, the ability to significantly decrease their likelihood would seem to be of great benefit. A Phase II clinical trial utilizing lower doses of GTx-758 (G200712) is currently being performed that will determine if similar effects on serum free testosterone, PSA and hot flashes can be shown with a lower rate of VTEs. Clinical trial information: NCT01326312.

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