scholarly journals Identification and Characterization of an Exonic Duplication in PALB2 in a Man with Synchronous Breast and Prostate Cancer

2022 ◽  
Vol 23 (2) ◽  
pp. 667
Author(s):  
Ahmed Bouras ◽  
Cyril Lafaye ◽  
Melanie Leone ◽  
Zine-Eddine Kherraf ◽  
Tanguy Martin-Denavit ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Sanger Sequencing ◽  
Repetitive Sequences ◽  
Strand Break ◽  
Functional Protein ◽  
Interacting Protein ◽  
Cancer Data ◽  
Targeted Next Generation Sequencing ◽  
Pathogenic Variants ◽  
Increased Risk

PALB2 (partner and localizer of BRCA2), as indicated by its name, is a BRCA2-interacting protein that plays an important role in homologous recombination (HR) and DNA double-strand break (DSB) repair. While pathogenic variants of PALB2 have been well proven to confer an increased risk of breast cancer, data on its involvement in prostate cancer (PrC) have not been clearly demonstrated. We investigated, using targeted next generation sequencing (NGS), a 59-year-old Caucasian man who developed synchronous breast and prostate cancers. This genetic investigation allowed to identify an intragenic germline heterozygous duplication in PALB2, implicating intronic repetitive sequences spanning exon 11. This variant was confirmed by multiplex ligation probe amplification (MLPA), and genomic breakpoints have been identified and characterized at the nucleotide level (c.3114-811_3202-1756dup) using an approach based on walking PCR, long range PCR, and Sanger sequencing. RT-PCR using mRNA extracted from lymphocytes and followed by Sanger sequencing revealed a tandem duplication r.3114_3201dup; p.(Gly1068Glufs * 14). This duplication results in the synthesis of a truncated, and most-likely, non-functional protein. These findings expand the phenotypic spectrum of PALB2 variants and may improve the yield of genetic diagnoses in this field.

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

Cancers ◽  
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.

scholarly journals The evolving role of germline genetic testing and management in prostate cancer: Report from the Princess Margaret Cancer Centre International Retreat

2021 ◽  
Vol 15 (12) ◽  
Author(s):  
Roderick Clark ◽  
Miran Kenk ◽  
Kristen McAlpine ◽  
Emily Thain ◽  
Kirsten M. Farncombe ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Genetic Testing ◽  
Genetic Risk ◽  
Genetic Disorders ◽  
Future Research ◽  
Policy Action ◽  
Cancer Centre ◽  
Pathogenic Variants ◽  
Increased Risk ◽  
International Experts

Introduction: Prostate cancer is a significant cause of cancer mortality. It has been well-established that certain germline pathogenic variants confer both an increased risk of being diagnosed with prostate cancer and dying of prostate cancer.1 There are exciting developments in both the availability of genetic testing and opportunities for improved treatment of patients. On August 19, 2020, the Princess Margaret Cancer Centre in Toronto, Ontario, hosted a virtual retreat, bringing together international experts in urology, medical oncology, radiation oncology, medical genetics, and translational research, as well as a patient representative. We are pleased to provide this manuscript as a review of those proceedings for Canadian clinicians. Recommendations: We drafted several recommendations for future research and policy action based on this meeting: 1) Need for increased access to funding for germline testing for the common genetic disorders associated with increased risk of prostate cancer. 2) A need for increased research into identifying genetic factors influencing risk stratification, treatment response, and outcomes of prostate cancer within Canadian populations at increased genetic risk for prostate cancer. 3) Need for increased awareness about genetic risk factors among the Canadian public. 4) Need for research on patient perspectives and psychosocial outcomes in individuals identified to be at increased genetic risk of prostate cancer. 5) We support the creation of specialized multidisciplinary clinics that specialize in tailored care for patients at increased genetic risk of prostate cancer.

scholarly journals RAD51 and XRCC3 Polymorphisms Are Associated with Increased Risk of Prostate Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Maria Nowacka-Zawisza ◽  
Agata Raszkiewicz ◽  
Tomasz Kwasiborski ◽  
Ewa Forma ◽  
Magdalena Bryś ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Strand Break ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Dna Double Strand Break ◽  
Repair Efficiency ◽  
Increased Risk ◽  
Pcr Rflp ◽  
Repair Genes

Genetic polymorphisms in DNA repair genes may affect DNA repair efficiency and may contribute to the risk of developing cancer. The aim of our study was to investigate single nucleotide polymorphisms (SNPs) in RAD51 (rs2619679, rs2928140, and rs5030789) and XRCC3 (rs1799796) involved in DNA double-strand break repair and their relationship to prostate cancer. The study group included 99 men diagnosed with prostate cancer and 205 cancer-free controls. SNP genotyping was performed using the PCR-RFLP method. A significant association was detected between RAD51 rs5030789 polymorphism and XRCC3 rs1799796 polymorphism and an increased risk of prostate cancer. Our results indicate that RAD51 and XRCC3 polymorphism may contribute to prostate cancer.

scholarly journals Genetic investigation of 211 Chinese families expands the mutational and phenotypical spectra of hereditary retinopathy genes through targeted sequencing technology

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Zhouxian Bai ◽  
Yanchuan Xie ◽  
Lina Liu ◽  
Jingzhi Shao ◽  
Yuying Liu ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
Molecular Genetic ◽  
Gene Mutations ◽  
Central China ◽  
Targeted Sequencing ◽  
Sequencing Data ◽  
Targeted Next Generation Sequencing ◽  
Pathogenic Variants ◽  
Number Of Patients ◽  
Ophthalmologic Examination

Abstract Background Hereditary retinopathy is a significant cause of blindness worldwide. Despite the discovery of many mutations in various retinopathies, a large number of patients remain genetically undiagnosed. Targeted next-generation sequencing of the human genome is a suitable approach for the molecular diagnosis of retinopathy. Methods We describe a cohort of 211 families from central China with various forms of retinopathy; 95 patients were investigated using multigene panel sequencing, and the other 116 with suspected Leber hereditary optic neuropathy (LHON) were tested by Sanger sequencing. The detected variation of targeted sequencing was verified by PCR-based Sanger sequencing. We performed a comprehensive analysis of the cases using sequencing data and ophthalmologic examination information. Results Potential causal mutations were identified in the majority of families with retinopathy (57.9% of 95 families) and suspected LHON (21.6% of 116 families). There were 68 variants of a certain significance distributed in 31 known disease-causing genes in the 95 families; 37 of the variants are novel and have not been reported to be related to hereditary retinopathy. The NGS panel solution provided a 45.3% potential diagnostic rate for retinopathy families, with candidate gene mutations of undefined pathogenicity revealed in another 12.6%of the families. Conclusion Our study uncovered novel mutations and phenotypic aspects of retinopathy and demonstrated the genetic and clinical heterogeneity of related conditions. The findings show the detection rate of pathogenic variants in patients with hereditary retinopathy in central China as well as the diversity and gene distribution of these variants. The significance of molecular genetic testing for patients with hereditary retinopathy is also highlighted.

scholarly journals Detection and validation of six pathogenic variants in Chinese inherited heart disease patients using clinical whole-exome sequencing

2021 ◽  
Author(s):  
Lichao Cao ◽  
Fei Ye ◽  
Shuqi Xie ◽  
Ying Ba ◽  
Ying Zeng ◽  
...  
Keyword(s):  
Heart Disease ◽  
Next Generation Sequencing ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Targeted Next Generation Sequencing ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

The targeted next-generation sequencing (NGS) was employed in detecting the pathogenic mutations in inherited heart disease patients in the present study. Two main methods, the NGS and the classic Sanger sequencing, were used in this study. And, the whole-exome sequencing (WES) was specifically used in this study.

scholarly journals Temporal association of prostate cancer incidence with World Trade Center rescue/recovery work

2021 ◽  
pp. oemed-2021-107405
Author(s):  
David G Goldfarb ◽  
Rachel Zeig-Owens ◽  
Dana Kristjansson ◽  
Jiehui Li ◽  
Robert M Brackbill ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
New York ◽  
World Trade ◽  
Profile Likelihood ◽  
World Trade Center ◽  
New York State ◽  
York State ◽  
Cancer Data ◽  
Increased Risk ◽  
Trade Center

BackgroundThe World Trade Center (WTC) attacks on 11 September 2001 created a hazardous environment with known and suspected carcinogens. Previous studies have identified an increased risk of prostate cancer in responder cohorts compared with the general male population.ObjectivesTo estimate the length of time to prostate cancer among WTC rescue/recovery workers by determining specific time periods during which the risk was significantly elevated.MethodsPerson-time accruals began 6 months after enrolment into a WTC cohort and ended at death or 12/31/2015. Cancer data were obtained through linkages with 13 state cancer registries. New York State was the comparison population. We used Poisson regression to estimate hazard ratios and 95% CIs; change points in rate ratios were estimated using profile likelihood.ResultsThe analytic cohort included 54 394 male rescue/recovery workers. We observed 1120 incident prostate cancer cases. During 2002–2006, no association with WTC exposure was detected. Beginning in 2007, a 24% increased risk (HR: 1.24, 95% CI 1.16 to 1.32) was observed among WTC rescue/recovery workers when compared with New York State. Comparing those who arrived earliest at the disaster site on the morning of 11 September 2001 or any time on 12 September 2001 to those who first arrived later, we observed a positive, monotonic, dose-response association in the early (2002–2006) and late (2007–2015) periods.ConclusionsRisk of prostate cancer was significantly elevated beginning in 2007 in the WTC combined rescue/recovery cohort. While unique exposures at the disaster site might have contributed to the observed effect, screening practices including routine prostate specific antigen screening cannot be discounted.

598: Increased Risk of Newly Diagnosed Comorbidities in Prostate Cancer Patients Treated with Androgen Deprivation Therapy

2007 ◽  
Vol 177 (4S) ◽  
pp. 200-200 ◽  
Author(s):  
Andrea Gallina ◽  
Pierre I. Karakiewicz ◽  
Jochen Walz ◽  
Claudio Jeldres ◽  
Quoc-Dien Trinh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation ◽  
Newly Diagnosed ◽  
Increased Risk

464: Is Obesity Associated with more Aggressive Prostate Cancer? (Data from Capsure)

2004 ◽  
Vol 171 (4S) ◽  
pp. 124-124 ◽  
Author(s):  
Christopher J. Kane ◽  
William W. Bassett ◽  
Natalia Sadetsky ◽  
Stephanie J. Silva ◽  
David J. Pasta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Aggressive Prostate Cancer ◽  
Cancer Data

Male Osteoporosis

2013 ◽  
Vol 22 (04) ◽  
pp. 260-266 ◽  
Author(s):  
S. P. Tuck ◽  
R. M. Francis ◽  
B. C. Hanusch
Keyword(s):  
Prostate Cancer ◽  
Older Men ◽  
Good Evidence ◽  
Male Osteoporosis ◽  
Fracture Rate ◽  
Common Cause ◽  
Increased Risk ◽  
Osteoporosis In Men ◽  
Considerable Morbidity ◽  
Secondary Causes

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.

Sign in / Sign up

Export Citation Format

Share Document