Polymorphisms in the CYP1B1 gene are associated with increased risk of prostate cancer

SummaryMale osteoporosis is common and results in considerable morbidity and mortality. There are distinct differences in the normal aging of bone between the genders, which result in a lower fracture rate in men. Men who suffer from osteoporosis are much more likely than women to have secondary causes. The identification and treatment of these secondary causes, wherever possible, will result in substantial improvements in BMD. There is now evidence for use of many of the existing agents to treat osteoporosis in men. In younger hypogonadal men testosterone replacement is worth considering, but in older men especially the over sixties this is less effective and there is an increased risk of adverse cardiovascular and prostatic outcomes. Prostate cancer is an increasingly common cause, which is partially the result of the success of ADT. There is now good evidence for the use of bisphosphonates and denosumab in this group of patients. HIV, whilst not being specific to men, is an increasingly recognised cause of male osteoporosis. The reasons for this are multifactorial and some may well be attributable to the anti-retroviral therapy itself. There is emerging evidence of an increased fracture risk in HIV infected individuals. The bone loss can be prevented by the use of bisphosphonates.

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Faculty Opinions recommendation of Increased risk of high-grade prostate cancer among infertile men.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.2692956.2355054 ◽

2010 ◽

Author(s):

Dolores Lamb ◽

Kathleen Hwang

Keyword(s):

Prostate Cancer ◽

High Grade ◽

Infertile Men ◽

Increased Risk

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Prostate Cancer

10.1093/oso/9780190676827.003.0020 ◽

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.

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Rare Germline Pathogenic Variants Identified by Multigene Panel Testing and the Risk of Aggressive Prostate Cancer

Cancers ◽

10.3390/cancers13071495 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1495

Author(s):

Tú Nguyen-Dumont ◽

James G. Dowty ◽

Robert J. MacInnis ◽

Jason A. Steen ◽

Moeen Riaz ◽

...

Keyword(s):

Prostate Cancer ◽

Risk Prediction ◽

Prediction Models ◽

Risk Prediction Models ◽

Aggressive Prostate Cancer ◽

Panel Testing ◽

Pathogenic Variants ◽

Increased Risk ◽

Predisposition Genes ◽

Rare Genetic Variants

While gene panel sequencing is becoming widely used for cancer risk prediction, its clinical utility with respect to predicting aggressive prostate cancer (PrCa) is limited by our current understanding of the genetic risk factors associated with predisposition to this potentially lethal disease phenotype. This study included 837 men diagnosed with aggressive PrCa and 7261 controls (unaffected men and men who did not meet criteria for aggressive PrCa). Rare germline pathogenic variants (including likely pathogenic variants) were identified by targeted sequencing of 26 known or putative cancer predisposition genes. We found that 85 (10%) men with aggressive PrCa and 265 (4%) controls carried a pathogenic variant (p < 0.0001). Aggressive PrCa odds ratios (ORs) were estimated using unconditional logistic regression. Increased risk of aggressive PrCa (OR (95% confidence interval)) was identified for pathogenic variants in BRCA2 (5.8 (2.7–12.4)), BRCA1 (5.5 (1.8–16.6)), and ATM (3.8 (1.6–9.1)). Our study provides further evidence that rare germline pathogenic variants in these genes are associated with increased risk of this aggressive, clinically relevant subset of PrCa. These rare genetic variants could be incorporated into risk prediction models to improve their precision to identify men at highest risk of aggressive prostate cancer and be used to identify men with newly diagnosed prostate cancer who require urgent treatment.

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Social Jetlag and Prostate Cancer Incidence in Alberta’s Tomorrow Project: A Prospective Cohort Study

Cancers ◽

10.3390/cancers12123873 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3873

Author(s):

Liang Hu ◽

Andrew Harper ◽

Emily Heer ◽

Jessica McNeil ◽

Chao Cao ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Risk ◽

Cancer Incidence ◽

Repeated Measures ◽

Prospective Cohort ◽

Prostate Cancer Risk ◽

Absolute Difference ◽

Prostate Cancer Incidence ◽

Social Jetlag ◽

Increased Risk

We investigated the association of social jetlag (misalignment between the internal clock and socially required timing of activities) and prostate cancer incidence in a prospective cohort in Alberta, Canada. Data were collected from 7455 cancer-free men aged 35–69 years enrolled in Alberta’s Tomorrow Project (ATP) from 2001–2007. In the 2008 survey, participants reported usual bed- and wake-times on weekdays and weekend days. Social jetlag was defined as the absolute difference in waking time between weekday and weekend days, and was categorized into three groups: 0–<1 h (from 0 to anything smaller than 1), 1–<2 h (from 1 to anything smaller than 2), and 2+ h. ATP facilitated data linkage with the Alberta Cancer Registry in June 2018 to determine incident prostate cancer cases (n = 250). Hazard ratios (HR) were estimated using Cox proportional hazards regressions, adjusting for a range of covariates. Median follow-up was 9.57 years, yielding 68,499 person-years. Baseline presence of social jetlag of 1–<2 h (HR = 1.52, 95% CI: 1.10 to 2.01), and 2+ hours (HR = 1.69, 95% CI: 1.15 to 2.46) were associated with increased prostate cancer risk vs. those reporting no social jetlag (p for trend = 0.004). These associations remained after adjusting for sleep duration (p for trend = 0.006). With respect to chronotype, the association between social jetlag and prostate cancer risk remained significant in men with early chronotypes (p for trend = 0.003) but attenuated to null in men with intermediate (p for trend = 0.150) or late chronotype (p for trend = 0.381). Our findings suggest that greater than one hour of habitual social jetlag is associated with an increased risk of prostate cancer. Longitudinal studies with repeated measures of social jetlag and large samples with sufficient advanced prostate cancer cases are needed to confirm these findings.

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Elevated Expression of Glycerol-3-Phosphate Phosphatase as a Biomarker of Poor Prognosis and Aggressive Prostate Cancer

Cancers ◽

10.3390/cancers13061273 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1273

Author(s):

Mohamed Amine Lounis ◽

Veronique Ouellet ◽

Benjamin Péant ◽

Christine Caron ◽

Zhenhong Li ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Metastasis ◽

Biochemical Recurrence ◽

Poor Prognosis ◽

Cox Regression ◽

Specific Antigen ◽

Metabolic Stress ◽

Cancer Specific Survival ◽

High Risk Prostate Cancer ◽

Increased Risk

The limitations of the biomarker prostate-specific antigen (PSA) necessitate the pursuit of biomarkers capable of better identifying high-risk prostate cancer (PC) patients in order to improve their therapeutic management and outcomes. Aggressive prostate tumors characteristically exhibit high rates of glycolysis and lipogenesis. Glycerol 3-phosphate phosphatase (G3PP), also known as phosphoglycolate phosphatase (PGP), is a recently identified mammalian enzyme, shown to play a role in the regulation of glucose metabolism, lipogenesis, lipolysis, and cellular nutrient-excess detoxification. We hypothesized that G3PP may relieve metabolic stress in cancer cells and assessed the association of its expression with PC patient prognosis. Using immunohistochemical staining, we assessed the epithelial expression of G3PP in two different radical prostatectomy (RP) cohorts with a total of 1797 patients, for whom information on biochemical recurrence (BCR), metastasis, and mortality was available. The association between biomarker expression, biochemical recurrence (BCR), bone metastasis, and prostate cancer-specific survival was established using log-rank and multivariable Cox regression analyses. High expression of G3PP in PC epithelial cells is associated with an increased risk of BCR, bone metastasis, and PC-specific mortality. Multivariate analysis revealed high G3PP expression in tumors as an independent predictor of BCR and bone metastasis development. High G3PP expression in tumors from patients eligible for prostatectomies is a new and independent prognostic biomarker of poor prognosis and aggressive PC for recurrence, bone metastasis, and mortality.

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Prostate cancer diagnosis is associated with an increased risk of erectile dysfunction after prostate biopsy

Yearbook of Urology ◽

10.1016/j.yuro.2013.02.011 ◽

2013 ◽

Vol 2013 ◽

pp. 92-93

Author(s):

A.W. Shindel

Keyword(s):

Prostate Cancer ◽

Erectile Dysfunction ◽

Cancer Diagnosis ◽

Prostate Biopsy ◽

Prostate Cancer Diagnosis ◽

Increased Risk

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CHEK2∗1100delC Mutation and Risk of Prostate Cancer

Prostate Cancer ◽

10.1155/2014/294575 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 24

Author(s):

Victoria Hale ◽

Maren Weischer ◽

Jong Y. Park

Keyword(s):

Prostate Cancer ◽

Current Knowledge ◽

Prostate Cancer Screening ◽

Critical Role ◽

Prostate Cancer Risk ◽

Conclusive Evidence ◽

Increased Risk ◽

History Of ◽

Cancer Studies

Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer.CHEK2plays a critical role in DNA replication by responding to double-stranded breaks. In this review, we provide an overview of the current knowledge of the role of a genetic variant, 1100delC, ofCHEK2on prostate cancer risk and discuss the implication for potential translation of this knowledge into clinical practice. Currently, twelve articles that discussedCHEK2∗1100delC and its association with prostate cancer were identified. Of the twelve prostate cancer studies, five studies had independent data to draw conclusive evidence from. The pooled results of OR and 95% CI were 1.98 (1.23–3.18) for unselected cases and 3.39 (1.78–6.47) for familial cases, indicating thatCHEK2∗1100delC mutation is associated with increased risk of prostate cancer. Screening for CHEK2∗1100delC should be considered in men with a familial history of prostate cancer.

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