scholarly journals Evaluation of polygenic risk scores for predicting breast and prostate cancer risk

2011 ◽  
pp. n/a-n/a ◽  
Author(s):  
Mitchell J. Machiela ◽  
Chia-Yen Chen ◽  
Constance Chen ◽  
Stephen J. Chanock ◽  
David J. Hunter ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Prostate Cancer Risk ◽  
Risk Scores ◽  
Polygenic Risk ◽  
Breast And Prostate Cancer

scholarly journals Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores

2017 ◽  
Vol 35 (20) ◽  
pp. 2240-2250 ◽  
Author(s):  
Julie Lecarpentier ◽  
Valentina Silvestri ◽  
Karoline B. Kuchenbaecker ◽  
Daniel Barrowdale ◽  
Joe Dennis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Cancer Susceptibility ◽  
Prostate Cancer Risk ◽  
Risk Scores ◽  
Cancer Risks ◽  
Prostate Cancer Susceptibility ◽  
Common Genetic Variants ◽  
Breast And Prostate Cancer ◽  
Male Carriers

Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated—for the first time to our knowledge—associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/ 2 mutations and implications for cancer risk prediction. Materials and Methods We genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. Results In male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; P = 8.6 × 10−6). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; P = 3.2 × 10−9). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of BRCA1 mutations and from 19% to 61% for carriers of BRCA2 mutations, respectively. Conclusion PRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.

scholarly journals Breast and prostate cancer risk: the interplay of polygenic risk, rare pathogenic germline variants, and family history

2021 ◽  
Author(s):  
Emadeldin Hassanin ◽  
Patrick May ◽  
Rana Aldisi ◽  
Isabel Spier ◽  
Andreas J. Forstner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Cancer Risk ◽  
Prostate Cancer Risk ◽  
Germline Variants ◽  
Polygenic Risk ◽  
Breast And Prostate Cancer

scholarly journals Breast and prostate cancer risk: the interplay of polygenic risk, high-impact monogenic variants, and family history

2021 ◽  
Author(s):  
Emadeldin Hassanin ◽  
Patrick May ◽  
Rana Aldisi ◽  
Isabel Spier ◽  
Andreas J. Forstner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Cancer Risk ◽  
Cumulative Incidence ◽  
Cancer Susceptibility ◽  
Prostate Cancer Risk ◽  
High Impact ◽  
Polygenic Risk ◽  
Cancer Susceptibility Genes ◽  
Breast And Prostate Cancer

Purpose Investigate to which extent polygenic risk scores (PRS), high-impact monogenic variants, and family history affect breast and prostate cancer risk by assessing cancer prevalence and cancer cumulative lifetime incidence. Methods 200,643 individuals from the UK Biobank were stratified as follows: 1. carriers or non-carriers of high impact constitutive, monogenic variants in cancer susceptibility genes, 2. high or non-high PRS (90th percentile threshold), 3. with or without a family history of cancer. Multivariable logistic regression was used to compare the odds ratio (OR) across the different groups while Cox proportional hazards models were used to compute the cumulative incidence through life. Results Breast and prostate cancer cumulative incidence by age 70 is 7% and 5% for non-carriers with non-high PRS and reaches 37% and 32% among carriers of high-impact variants in cancer susceptibility genes with high PRS. The additional presence of family history is associated with a further increase of the risk of developing cancer reaching an OR of 14 and 21 for breast and prostate cancer, respectively. Conclusion High PRS confers a cancer risk comparable to high-impact monogenic variants. Family history, monogenic variants, and PRS contribute additively to breast and prostate cancer risk.

scholarly journals Evaluating the Association between Artificial Light-at-Night Exposure and Breast and Prostate Cancer Risk in Spain (MCC-Spain Study)

2018 ◽  
Vol 126 (4) ◽  
pp. 047011 ◽  
Author(s):  
Ariadna Garcia-Saenz ◽  
Alejandro Sánchez de Miguel ◽  
Ana Espinosa ◽  
Antonia Valentin ◽  
Núria Aragonés ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Prostate Cancer Risk ◽  
Artificial Light ◽  
Light At Night ◽  
Breast And Prostate Cancer

Association of glutamate carboxypeptidase II (GCPII) haplotypes with breast and prostate cancer risk

Gene ◽  
2013 ◽  
Vol 516 (1) ◽  
pp. 76-81 ◽  
Author(s):  
Shree Divyya ◽  
Shaik Mohammad Naushad ◽  
Anthony Addlagatta ◽  
P.V.L.N. Murthy ◽  
Ch. Ram Reddy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Prostate Cancer Risk ◽  
Glutamate Carboxypeptidase Ii ◽  
Breast And Prostate Cancer ◽  
Glutamate Carboxypeptidase

scholarly journals ABO blood group alleles and prostate cancer risk: Results from the breast and prostate cancer cohort consortium (BPC3)

The Prostate ◽  
2015 ◽  
Vol 75 (15) ◽  
pp. 1677-1681 ◽  
Author(s):  
Sarah C. Markt ◽  
Irene M. Shui ◽  
Robert H. Unger ◽  
Yuksel Urun ◽  
Christine D. Berg ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Blood Group ◽  
Prostate Cancer Risk ◽  
Abo Blood Group ◽  
Breast And Prostate Cancer

scholarly journals A Polygenic Risk Score Predicts Incident Prostate Cancer Risk in Older Men but Does Not Select for Clinically Significant Disease

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5815
Author(s):  
Andrew Bakshi ◽  
Moeen Riaz ◽  
Suzanne G. Orchard ◽  
Prudence R. Carr ◽  
Amit D. Joshi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Risk Score ◽  
Prostate Cancer Risk ◽  
Older Men ◽  
Polygenic Risk Score ◽  
Gleason Grade ◽  
Polygenic Risk ◽  
Clinically Significant ◽  
Significant Disease

Despite the high prevalence of prostate cancer in older men, the predictive value of a polygenic risk score (PRS) remains uncertain in men aged ≥70 years. We used a 6.6 million-variant PRS to predict the risk of incident prostate cancer in a prospective study of 5701 men of European descent aged ≥70 years (mean age 75 years) enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial. The study endpoint was prostate cancer, including metastatic or non-metastatic disease, confirmed by an expert panel. After excluding participants with a history of prostate cancer at enrolment, we used a multivariable Cox proportional hazards model to assess the association between the PRS and incident prostate cancer risk, adjusting for covariates. Additionally, we examined the distribution of Gleason grade groups by PRS group to determine if a higher PRS was associated with higher grade disease. We tested for interaction between the PRS and aspirin treatment. Logistic regression was used to independently assess the association of the PRS with prevalent (pre-trial) prostate cancer, reported in medical histories. During a median follow-up time of 4.6 years, 218 of the 5701 participants (3.8%) were diagnosed with prostate cancer. The PRS predicted incident risk with a hazard ratio (HR) of 1.52 per standard deviation (SD) (95% confidence interval (CI) 1.33–1.74, p < 0.001). Men in the top quintile of the PRS distribution had an almost three times higher risk of prostate cancer than men in the lowest quintile (HR = 2.99 (95% CI 1.90–4.27), p < 0.001). However, a higher PRS was not associated with a higher Gleason grade groups. We found no interaction between aspirin treatment and the PRS for prostate cancer risk. The PRS was also associated with prevalent prostate cancer (odds ratio = 1.80 per SD (95% CI 1.65–1.96), p < 0.001).While a PRS for prostate cancer is strongly associated with incident risk in men aged ≥70 years, the clinical utility of the PRS as a biomarker is currently limited by its inability to select for clinically significant disease.

scholarly journals Do sex hormones confound or mediate the effect of chronotype on breast and prostate cancer? A Mendelian randomization study.

2021 ◽  
Author(s):  
Bryony L Hayes ◽  
Timothy Robinson ◽  
Siddhartha P. Kar ◽  
Katherine S Ruth ◽  
Konstantinos K Tsilidis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Cancer Risk ◽  
Protective Effect ◽  
Sex Hormones ◽  
Prostate Cancer Risk ◽  
Total Testosterone ◽  
Testosterone Levels ◽  
Bioavailable Testosterone ◽  
Breast And Prostate Cancer

BACKGROUND Previous research has demonstrated that a morning-preference chronotype is protective against both breast and prostate cancer. Sex hormones have been implicated in relation to both chronotype and the development of both cancers. This study aims to assess whether sex hormones confound or mediate the effect of chronotype on breast and prostate cancer risk using a Mendelian Randomization (MR) framework. METHODS We obtained genetic variants strongly (p<5x10-8) associated with chronotype and sex hormones (total testosterone, bioavailable testosterone, sex hormone binding globulin (SHBG), and oestradiol from previously published genome-wide association studies (GWAS) that had been undertaken in UK Biobank and 23andMe (n=244,207 females and n=205,527 males). These variants were used to investigate causal relationships with risk of breast and prostate cancer using summary data from the largest available consortia in breast (nCases/nControls=133,384/ 113,789) and prostate cancer (nCases/nControls=79,148/61,106). This was achieved using a series of MR approaches: univariable, bidirectional and multivariable. Results Overall, we found evidence for a protective effect of genetically predicted tendency towards morning preference on both breast (OR=0.93, 95% CI:0.88, 1.00) and prostate (OR=0.90, 95% CI:0.83, 0.97) cancer risk. There was evidence that an increased tendency to morning preference reduces bioavailable testosterone levels in both females (mean SD difference=-0.08, 95% CI:-0.12, -0.05) and males (mean SD difference=-0.06, 95% CI:-0.09, -0.03), and reduces total testosterone levels in females (mean SD difference=-0.07, 95% CI:-0.10, -0.03). We also found evidence to support higher total and bioavailable testosterone increasing the risk of breast cancer (OR=1.15, 95% CI:1.07, 1.23, OR=1.10, 95% CI:1.01, 1.19 respectively) and higher bioavailable testosterone increasing prostate cancer risk (OR=1.22, 95% CI:1.08, 1.37). While findings from univariable and bidirectional MR analyses indicated that testosterone may lie on the causal pathway between chronotype and cancer risk, there was evidence for a bidirectional association between chronotype and testosterone in females, implicating testosterone as both a confounder and mediator of the chronotype effect on breast cancer risk. However, the effects of chronotype remained largely unchanged when accounting for testosterone in multivariable MR, suggesting that any confounding or mediating effect is likely to be minimal. Conclusions This study has extended previous findings regarding the protective effect of chronotype on breast cancer and found evidence to suggest that morning preference also reduces prostate cancer risk in men. While testosterone levels were found to be closely linked with both chronotype and cancer risk, there was inconsistent evidence for the role of testosterone in mediating the effect of morning preference chronotype on both breast and prostate cancer. Findings regarding the potential protective effect of chronotype on both breast and prostate cancer risk are clinically interesting. However, this may not serve as a direct target for intervention, since it is difficult to modify someone's morning/evening preference. Given this, further studies are needed to investigate the mechanisms underlying this effect and to identify other potential modifiable intermediates.

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