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, 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 Association of 17 prostate cancer susceptibility loci with prostate cancer risk in Chinese men

The Prostate ◽  
2009 ◽  
Vol 70 (4) ◽  
pp. 425-432 ◽  
Author(s):  
Siqun Lilly Zheng ◽  
Ann W. Hsing ◽  
Jielin Sun ◽  
Lisa W. Chu ◽  
Kai Yu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Cancer Susceptibility ◽  
Prostate Cancer Risk ◽  
Susceptibility Loci ◽  
Chinese Men ◽  
Prostate Cancer Susceptibility

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

Cancer risks associated with the HOXB13 c.251G> A variant in men and women referred for hereditary cancer genetic testing.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13653-e13653
Author(s):  
Melanie Jones ◽  
Eric Thomas Rosenthal ◽  
Karen Copeland ◽  
John Kidd ◽  
Ryan Bernhisel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Genetic Testing ◽  
Cancer Risk ◽  
Hereditary Cancer ◽  
Prostate Cancer Risk ◽  
Cancer Risks ◽  
Increased Risk ◽  
Males And Females ◽  
Male Carriers ◽  
Female Carriers

e13653 Background: The HOXB13 c.251G > A (p.G84E) variant is associated with increased prostate cancer risk, possibly at younger ages. Studies on this variant have focused primarily on men, although genetic testing for hereditary cancer risk is most often performed in women. There remains a need to assess whether male and female carriers of this variant have increased risk for other cancers. Methods: We identified male and female carriers of the HOXB13 c.251G > A (p.G84E) variant among individuals referred for hereditary cancer panel genetic testing from October 2018 – December 2019. Non-carriers had no pathogenic variants in any gene or variants of uncertain significance in HOXB13. Personal and family (1st- and 2nd-degree relative) cancer histories were obtained from provider-completed test request forms. Multivariable logistic regression (MLR) models were conducted separately for males and females to estimate cancer risks for the variant as odds ratios (ORs), and 95% Wald confidence intervals (CIs) adjusted for age, ancestry and personal/family cancer history. Results: The analysis included 197,978 patients: 4.5% (8,998/197,978) male and 95.5% (188,980/197,978) female. The HOXB13 variant was present in 0.44% (40/8,998) of tested males, 45% (18/40) of whom had a diagnosis of prostate cancer. The variant was present in 0.32% (621/188,980) of tested females. Male carriers with prostate cancer were diagnosed at younger ages (median, 56; Interquartile ratio [IQR], 52, 62) than non-carriers (median, 63; IQR, 57,70), but this difference was not statistically significant. The MLR model calculated a 3.30 OR for prostate cancer in male carriers of c.251C > A ( P = 0.01; 95% CI 1.30-8.39). In an analysis combining males and females, carriers were significantly more likely to report prostate cancer in a family member than non-carriers ( P = 3.5 x 10−7; OR 1.61, 95% CI 1.34-1.93). There was no apparent association with increased risk for other cancers among carriers versus non-carriers, or among relatives of carriers compared with relatives of non-carriers. Conclusions: The HOXB13 c.251G > A (p.G84E) variant was associated with significantly increased risk of prostate cancer, confirming previously published studies. We found no evidence of association with other cancers. For unaffected male carriers, who may frequently be identified through testing of a female relative, identification of this HOXB13 variant provides an opportunity for more precise prostate cancer risk stratification and screening.

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

scholarly journals Germline genetic variation in prostate susceptibility does not predict outcomes in the chemoprevention trials PCPT and SELECT

2019 ◽  
Vol 23 (2) ◽  
pp. 333-342
Author(s):  
Mahbubl Ahmed ◽  
◽  
Chee Goh ◽  
Edward Saunders ◽  
Clara Cieza-Borrella ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Susceptibility ◽  
Risk Scores ◽  
Polygenic Risk Score ◽  
Logistic Regression Models ◽  
Prostate Cancer Susceptibility ◽  
Develop Prostate Cancer ◽  
Risk Snps ◽  
Chemoprevention Agent ◽  
Select Trial

Abstract Background The development of prostate cancer can be influenced by genetic and environmental factors. Numerous germline SNPs influence prostate cancer susceptibility. The functional pathways in which these SNPs increase prostate cancer susceptibility are unknown. Finasteride is currently not being used routinely as a chemoprevention agent but the long term outcomes of the PCPT trial are awaited. The outcomes of the SELECT trial have not recommended the use of chemoprevention in preventing prostate cancer. This study investigated whether germline risk SNPs could be used to predict outcomes in the PCPT and SELECT trial. Methods Genotyping was performed in European men entered into the PCPT trial (n = 2434) and SELECT (n = 4885). Next generation genotyping was performed using Affymetrix® Eureka™ Genotyping protocols. Logistic regression models were used to test the association of risk scores and the outcomes in the PCPT and SELECT trials. Results Of the 100 SNPs, 98 designed successfully and genotyping was validated for samples genotyped on other platforms. A number of SNPs predicted for aggressive disease in both trials. Men with a higher polygenic score are more likely to develop prostate cancer in both trials, but the score did not predict for other outcomes in the trial. Conclusion Men with a higher polygenic risk score are more likely to develop prostate cancer. There were no interactions of these germline risk SNPs and the chemoprevention agents in the SELECT and PCPT trials.

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

Prostate cancer susceptibility genes: lessons learned and challenges posed.

2003 ◽  
pp. 225-259 ◽  
Author(s):  
J Simard ◽  
M Dumont ◽  
D Labuda ◽  
D Sinnett ◽  
C Meloche ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Genetic Variants ◽  
Cancer Susceptibility ◽  
Susceptibility Genes ◽  
Screening Methods ◽  
Cancer Susceptibility Genes ◽  
Prostate Cancer Susceptibility ◽  
Common Genetic Variants

In most developed countries, prostate cancer is the most frequently diagnosed malignancy in men. The extent to which the marked racial/ethnic difference in its incidence rate is attributable to screening methods, environmental, hormonal and/or genetic factors remains unknown. A positive family history is among the strongest epidemiological risk factors for prostate cancer. It is now well recognized that the role of candidate genetic markers to this multifactorial malignancy is more difficult to identify than the identification of other cancer susceptibility genes. Indeed, despite the localization of several susceptibility loci, there has been limited success in identifying high-risk susceptibility genes analogous to BRCA1 or BRCA2 for breast and ovarian cancer. Nonetheless, three strong candidate susceptibility genes have been described, namely ELAC2 (chromosome 17p11/HPC2 region), 2'-5'-oligoadenylate-dependent ribonuclease L (RNASEL), a gene in the HPC1 region, and Macrophage Scavenger Receptor 1 (MSR1), a gene within a region of linkage on chromosome 8p. Additional studies using larger cohorts are needed to fully evaluate the role of these susceptibility genes in prostate cancer risk. It is also of interest to mention that a significant percentage of men with early-onset prostate cancer harbor germline mutation in the BRCA2 gene thus confirming its role as a high-risk prostate cancer susceptibility gene. Although initial segregation analyses supported the hypothesis that a number of rare highly penetrant loci contribute to the Mendelian inheritance of prostate cancer, current experimental evidence better supports the hypothesis that some of the familial risks may be due to inheritance of multiple moderate-risk genetic variants. In this regard, it is not surprising that analyses of genes encoding key proteins involved in androgen biosynthesis and action led to the observation of a significant association between a susceptibility to prostate cancer and common genetic variants in some of those genes.

Aspirin Use is Associated with Lower Prostate Cancer Risk in Male Carriers of BRCA Mutations

2013 ◽  
Vol 23 (2) ◽  
pp. 187-191 ◽  
Author(s):  
Matthew Cossack ◽  
Cameron Ghaffary ◽  
Patrice Watson ◽  
Carrie Snyder ◽  
Henry Lynch
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Prostate Cancer Risk ◽  
Brca Mutations ◽  
Male Carriers
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