scholarly journals PD38-06 WHICH GERMLINE GENES SHOULD BE TESTED FOR ASSESSING PROSTATE CANCER RISK? RESULTS FROM A LARGE POPULATION OF UNSELECTED CASES AND CONTROLS FROM UK BIOBANK

2020 ◽  
Vol 203 ◽  
pp. e803
Author(s):  
Yishuo Wu ◽  
Jun Wei ◽  
Zhuqing Shi ◽  
Richard Fantus ◽  
Siqun Zheng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Large Population ◽  
Prostate Cancer Risk ◽  
Uk Biobank ◽  
Germline Genes

scholarly journals O8A.4 Asbestos exposure and prostate cancer, really?

2019 ◽  
Vol 76 (Suppl 1) ◽  
pp. A71.1-A71
Author(s):  
Marie-Elise Parent ◽  
M Hugues Richard
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Asbestos Exposure ◽  
Large Population ◽  
Prostate Cancer Risk ◽  
Cumulative Exposure ◽  
Population Exposure ◽  
Specific Information ◽  
Chrysotile Asbestos ◽  
Increased Risk

BackgroundGeneral population exposure to asbestos from residential insulation and from environmental sources during childhood have recently been associated with prostate cancer. While asbestos fibers can be found in the prostate of workplace-exposed men at autopsy, few occupational studies have reported on asbestos exposure and prostate cancer incidence. We examined the association between lifetime occupational exposure to chrysotile asbestos and prostate cancer risk in a large population-based case-control study.MethodsCases were 1933 men with histologically-confirmed incident prostate cancer, aged ≤75 years, diagnosed in 2005–2009 in Montreal. Concurrently, 1994 population controls from the same residential area and age distribution were randomly selected from electoral lists. In-person interviews elicited detailed socio-demographics, lifestyle and work histories. Industrial hygienists used job-specific information to provide semi-quantitative evaluations of intensity and frequency of exposure to 345 chemical agents, including asbestos, and a measure of confidence in the evaluation. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer risk associated with exposure to chrysotile asbestos.ResultsAfter restriction to probable and definite exposure, and application of a 5 year lag, 12.5% of cases and 11.8% of controls were ever exposed to asbestos (OR=1.1, 95% CI 0.9–1.3). For duration of exposure, there was no increase in risk of overall prostate cancer in the lower tertiles of exposure but risk was elevated in the upper tertile (OR=1.6, 95% CI 1.2–2.2). Similarly, for cumulative exposure, risk was elevated in the upper tertile only (OR=1.5, 95% CI 1.1–2.1). Analyses considering tumor grades also showed a higher risk in the upper tertile of cumulative exposure for non-aggressive (OR=1.5, 95% CI 1.1–2.2) and especially aggressive (OR=1.9, 95% CI 1.2–3.0) cancers.ConclusionOur findings are consistent with an increased risk of prostate cancer with prolonged and high cumulative exposure to chrysotile asbestos, and particularly for the aggressive form of the disease.

scholarly journals Hematologic Markers and Prostate Cancer Risk: A Prospective Analysis in UK Biobank

2020 ◽  
Vol 29 (8) ◽  
pp. 1615-1626 ◽  
Author(s):  
Eleanor L. Watts ◽  
Aurora Perez-Cornago ◽  
Jaimal Kothari ◽  
Naomi E. Allen ◽  
Ruth C. Travis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Prostate Cancer Risk ◽  
Prospective Analysis ◽  
Uk Biobank

scholarly journals Appraising causal relationships of dietary, nutritional and physical-activity exposures with overall and aggressive prostate cancer: two-sample Mendelian-randomization study based on 79 148 prostate-cancer cases and 61 106 controls

2019 ◽  
Vol 49 (2) ◽  
pp. 587-596 ◽  
Author(s):  
Nabila Kazmi ◽  
Philip Haycock ◽  
Konstantinos Tsilidis ◽  
Brigid M Lynch ◽  
Therese Truong ◽  
...  
Keyword(s):  
Physical Activity ◽  
Prostate Cancer ◽  
Risk Factors ◽  
Cancer Risk ◽  
Serum Iron ◽  
Mendelian Randomization ◽  
Prostate Cancer Risk ◽  
Uk Biobank ◽  
Monounsaturated Fat ◽  
Aggressive Prostate Cancer

Abstract Background Prostate cancer is the second most common male cancer worldwide, but there is substantial geographical variation, suggesting a potential role for modifiable risk factors in prostate carcinogenesis. Methods We identified previously reported prostate cancer risk factors from the World Cancer Research Fund (WCRF)’s systematic appraisal of the global evidence (2018). We assessed whether each identified risk factor was causally associated with risk of overall (79 148 cases and 61 106 controls) or aggressive (15 167 cases and 58 308 controls) prostate cancer using Mendelian randomization (MR) based on genome-wide association-study summary statistics from the PRACTICAL and GAME-ON/ELLIPSE consortia. We assessed evidence for replication in UK Biobank (7844 prostate-cancer cases and 204 001 controls). Results WCRF identified 57 potential risk factors, of which 22 could be instrumented for MR analyses using single nucleotide polymorphisms. For overall prostate cancer, we identified evidence compatible with causality for the following risk factors (odds ratio [OR] per standard deviation increase; 95% confidence interval): accelerometer-measured physical activity, OR = 0.49 (0.33–0.72; P = 0.0003); serum iron, OR = 0.92 (0.86–0.98; P = 0.007); body mass index (BMI), OR = 0.90 (0.84–0.97; P = 0.003); and monounsaturated fat, OR = 1.11 (1.02–1.20; P = 0.02). Findings in our replication analyses in UK Biobank were compatible with our main analyses (albeit with wide confidence intervals). In MR analysis, height was positively associated with aggressive-prostate-cancer risk: OR = 1.07 (1.01–1.15; P = 0.03). Conclusions The results for physical activity, serum iron, BMI, monounsaturated fat and height are compatible with causality for prostate cancer. The results suggest that interventions aimed at increasing physical activity may reduce prostate-cancer risk, although interventions to change other risk factors may have negative consequences on other diseases.

scholarly journals Appraising causal relationships of dietary, nutritional and physical-activity exposures with overall and aggressive prostate cancer: two-sample Mendelian randomization study based on 79,148 prostate cancer cases and 61,106 controls

2019 ◽  
Author(s):  
Nabila Kazmi ◽  
Philip Haycock ◽  
Konstantinos Tsilidis ◽  
Brigid M. Lynch ◽  
Therese Truong ◽  
...  
Keyword(s):  
Physical Activity ◽  
Prostate Cancer ◽  
Risk Factors ◽  
Cancer Research ◽  
Cancer Risk ◽  
Serum Iron ◽  
Mendelian Randomization ◽  
Prostate Cancer Risk ◽  
Uk Biobank ◽  
Unsaturated Fat

SummaryBackgroundProstate cancer is the second most common male cancer worldwide, but there is substantial geographical variation suggesting a potential role for modifiable risk factors in prostate carcinogenesis.MethodsWe identified previously reported prostate cancer risk factors from the World Cancer Research Fund’s (WCRF) systematic appraisal of the global evidence (2018). We assessed whether each identified risk factor was causally associated with risk of overall (79,148 cases and 61,106 controls) or aggressive (15,167 cases and 58,308 controls) prostate cancer using Mendelian randomization (MR) based on genome wide association study (GWAS) summary statistics from the PRACTICAL and GAME-ON/ELLIPSE consortia. We assessed evidence for replication in UK Biobank (7,844 prostate cancer cases and 204,001 controls).FindingsWCRF identified 57 potential risk factors, of which 22 could be instrumented for MR analyses using single nucleotide polymorphisms (SNPs). In MR analyses for overall prostate cancer, we identified evidence compatible with causality for the following risk factors (odds ratio [OR] per standard deviation increase; 95% confidence interval): accelerometer-measured physical-activity, OR=0.49 (0.33-0.72; p=0.0003); serum iron, OR=0.92 (0.86-0.98; p=0.007); body mass index (BMI), OR=0.90 (0.84-0.97; p=0.003); and mono-unsaturated fat, OR=1.11 (1.02-1.20; p=0.02). Findings in our replication analyses in UK Biobank were compatible with our main analyses (albeit with wide confidence intervals). In MR analysis, height was positively associated with aggressive prostate cancer risk: OR=1.07 (1.01-1.15; p=0.03).InterpretationThe results for physical-activity, serum iron, BMI, mono-unsaturated fat and height are compatible with causality for prostate cancer but more research is needed to rule out violations of MR assumptions for some risk factors. The results suggest that interventions aimed at increasing physical activity may reduce prostate cancer risk, but the direction of effects of BMI, and iron are at odds with their effects on other diseases, so the overall public health impact of intervening on these need to be considered.FundingWorld Cancer Research Fund International (2015/1421), Cancer Research UK program grant (C18281/A19169), National Institute for Health Research, Bristol Biomedical Research Centre, and Victorian Cancer Agency (MCRF18005).

scholarly journals Metabolic syndrome biomarkers and prostate cancer risk in the UK Biobank

2020 ◽  
Vol 148 (4) ◽  
pp. 825-834
Author(s):  
Maria J. Monroy‐Iglesias ◽  
Beth Russell ◽  
Danielle Crawley ◽  
Naomi E. Allen ◽  
Ruth C. Travis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metabolic Syndrome ◽  
Cancer Risk ◽  
Prostate Cancer Risk ◽  
Uk Biobank ◽  
The Uk

The contribution of germline DNA damage response mutations on prostate cancer risk and prognosis: A UK Biobank whole-exome analysis.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 67-67
Author(s):  
Niedzica Camacho ◽  
Athena Matakidou
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Cancer Risk ◽  
Dna Damage Response ◽  
Prostate Cancer Risk ◽  
Population Based ◽  
Uk Biobank ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Damage Response

67 Background: Germline mutations in DNA Damage Response (DDR) genes such as BRCA2 and ATM have been associated with prostate cancer risk and aggressiveness. These associations are largely based on studies that ascertain for cancer diagnosis and family history and provide risk estimates with limited population-level accuracy. Here we evaluate the clinical significance of germline pathogenic variants in 20 DDR genes and a high-risk susceptibility coding variant in HOXB13 using whole exome sequences from (1) the UK Biobank (UKBB), a population-based cohort (300,000 participants) and (2) patients recruited in AZ clinical trials. Methods: Whole exomes from 6,987 prostate cancer patients (5,921 UKBB and 1,066 AZ) and 88,499 cancer-free males were analysed. Known and novel pathogenic variants were identified and associations with disease risk, age of onset, family history, response to hormonal therapy and overall survival were estimated (multiplicity corrected P value < 0.005). Results: HOXB13 G48E (1.36%), ATM (1.03%) and BRCA2 (0.99%) were the largest contributors to prostate cancer risk, each conferring an increase of ~4-fold, followed by CHEK2 with a moderate contribution (0.46%). No significant contributions to prostate cancer risk were observed for any of the other genes analysed. Family history of prostate cancer was not significantly enriched in any of the gene subpopulations of prostate cancer carriers and compared with non-carriers, there was no significant difference in the median age of disease onset. Analysis of clinical outcomes showed that BRCA2 carriers had a 4-fold increased risk of death (Cox PH HR p = 4.11E-12) and poorer overall survival (Log-Rank p = 4.60E-14), with 88% dying from prostate cancer compared to 49% of non- BRCA2 carriers (UKBB analysis). BRCA2 pathogenic mutations were also associated with early failure to hormonal therapy (Cox PH HR 2.38; p = 9.48E-04; AZ cohort analysis). HOXB13, ATM and CHEK2 mutations were not significantly associated with clinical outcomes. Conclusions: This is the largest study to date providing population-based estimates of prostate cancer risk and prognosis, highlighting BRCA2 carriers as a population in clinical need of early identification and targeted intervention. Updated analyses with data from the full 450,000 UKBB participants (9,000 prostate cancers) will be presented.

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