181 results match your criteria: "Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital[Affiliation]"
Breast cancer risks associated with missense variants in breast cancer susceptibility genes.
Genome Med
May 2022
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
Article Synopsis
- Protein truncating variants in genes like ATM and BRCA1 are linked to higher breast cancer risk, but the risks of missense variants remain unclear.
- A study involving over 59,000 breast cancer cases analyzed the impact of rare missense variants across several genes using advanced prediction techniques and statistical models.
- The analysis indicated that some missense variants in genes like ATM and BRCA1 could carry risks similar to truncating variants, while CHEK2 showed a different risk profile, and PALB2 variants had minimal association with breast cancer risk.
Genome-wide interaction analysis of menopausal hormone therapy use and breast cancer risk among 62,370 women.
Sci Rep
April 2022
Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
Article Synopsis
- * Through analysis of over 9 million genetic variants, the researchers found that none showed a significant interaction with MHT use for breast cancer risk, indicating common genetic variations do not heavily influence this association.
- * The strongest evidence of interaction was linked to a specific genetic variant, but overall findings suggest MHT's effect on breast cancer risk is primarily not affected by common genetic factors.
Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci.
Breast Cancer Res
April 2022
Department of Epidemiology, School of Public Health, University of Washington, 3980 15th Ave NE, Box 351619, Seattle, WA, 98195, USA.
Background: Mammographic density (MD) phenotypes, including percent density (PMD), area of dense tissue (DA), and area of non-dense tissue (NDA), are associated with breast cancer risk. Twin studies suggest that MD phenotypes are highly heritable. However, only a small proportion of their variance is explained by identified genetic variants.
View Article and Find Full Text PDFCorrection: Polygenic risk modeling for prediction of epithelial ovarian cancer risk.
Eur J Hum Genet
May 2022
University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK.
Pathology of Tumors Associated With Pathogenic Germline Variants in 9 Breast Cancer Susceptibility Genes.
JAMA Oncol
March 2022
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, England.
Article Synopsis
- Rare germline genetic variants in specific genes are linked to increased breast cancer risk, but their impact on different subtypes of the disease is not fully understood.
- The BRIDGES study analyzed data from 42,680 breast cancer patients and 46,387 controls, focusing on specific genetic mutations and their associations with tumor characteristics.
- Results showed that certain gene variants (like RAD51C, RAD51D, and BARD1) are primarily linked to triple-negative breast cancer, while others (like CHEK2) are associated with various subtypes, indicating varied genetic influence on breast cancer types.
Cancer Risks Associated With and Pathogenic Variants.
J Clin Oncol
May 2022
Center for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
Purpose: To provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in and for effective cancer risk management.
Methods: We used data from 3,184 and 2,157 families in the Consortium of Investigators of Modifiers of to estimate age-specific relative (RR) and absolute risks for 22 first primary cancer types adjusting for family ascertainment.
Results: PVs were associated with risks of male breast (RR = 4.
Rare germline copy number variants (CNVs) and breast cancer risk.
Commun Biol
January 2022
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.
View Article and Find Full Text PDFPolygenic risk modeling for prediction of epithelial ovarian cancer risk.
Eur J Hum Genet
March 2022
University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK.
Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction.
View Article and Find Full Text PDFCommon variants in breast cancer risk loci predispose to distinct tumor subtypes.
Breast Cancer Res
January 2022
Department of Biostatistics, Bloomberg School of Public Health, John Hopkins University, Baltimore, MD, USA.
Background: Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.
Methods: Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.
Risks of breast and ovarian cancer for women harboring pathogenic missense variants in BRCA1 and BRCA2 compared with those harboring protein truncating variants.
Genet Med
January 2022
Cancer Control and Population Science, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT. Electronic address:
Purpose: Germline genetic testing for BRCA1 and BRCA2 variants has been a part of clinical practice for >2 decades. However, no studies have compared the cancer risks associated with missense pathogenic variants (PVs) with those associated with protein truncating (PTC) variants.
Methods: We collected 582 informative pedigrees segregating 1 of 28 missense PVs in BRCA1 and 153 pedigrees segregating 1 of 12 missense PVs in BRCA2.
Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment.
Breast Cancer Res
August 2021
Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, 1066 CX, The Netherlands.
Background: Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients.
Methods: We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.
Genetic insights into biological mechanisms governing human ovarian ageing.
Nature
August 2021
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
Article Synopsis
- This research identifies 290 genetic factors linked to ovarian ageing by analyzing the age at natural menopause in 200,000 European women, highlighting how genetics can influence reproductive lifespan.* -
- The study reveals that these genetic variants are connected to DNA damage response processes that impact ovarian reserve and depletion rates, suggesting potential therapeutic targets.* -
- Manipulating these pathways in experimental models showed promise in boosting fertility and extending reproductive longevity, while also indicating benefits and risks for women's overall health, such as improved bone health but increased cancer risk.*
Mendelian randomisation study of smoking exposure in relation to breast cancer risk.
Br J Cancer
October 2021
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Background: Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk.
Methods: We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates.
Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores.
J Natl Cancer Inst
January 2022
Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
Background: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.
Methods: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).
Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element.
Am J Hum Genet
July 2021
The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London SW7 3RP, UK. Electronic address:
A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3.
View Article and Find Full Text PDFThe predictive ability of the 313 variant-based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant.
Genet Med
September 2021
Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Purpose: To evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes.
Methods: We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS and CBC risk.
Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?
Cancers (Basel)
May 2021
Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea.
In this study we aim to examine gene-environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors.
View Article and Find Full Text PDFAuthor Correction: A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.
Nat Commun
May 2021
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-23162-4.
View Article and Find Full Text PDFA case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.
Nat Commun
February 2021
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies.
View Article and Find Full Text PDFCYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers.
Br J Cancer
February 2021
The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.
Background: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk.
Methods: We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women.
Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.
N Engl J Med
February 2021
The authors' affiliations are as follows: the Centre for Cancer Genetic Epidemiology, Departments of Public Health and Primary Care (L.D., S. Carvalho, J.A., K.A.P., Q.W., M.K.B., J.D., B.D., N. Mavaddat, K. Michailidou, A.C.A., P.D.P.P., D.F.E.) and Oncology (C.L., P.A.H., C. Baynes, D.M.C., L.F., V.R., M. Shah, P.D.P.P., A.M.D., D.F.E.), University of Cambridge, Cambridge, the Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine (A. Campbell, D.J.P.), and the Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology (D.J.P.), University of Edinburgh, the Cancer Research UK Edinburgh Centre (D.A.C., J.F.), and the Usher Institute of Population Health Sciences and Informatics, University of Edinburgh Medical School (A. Campbell, J.F.), Edinburgh, the Divisions of Informatics, Imaging, and Data Sciences (E.F.H.), Cancer Sciences (A. Howell), Population Health, Health Services Research, and Primary Care (A. Lophatananon, K. Muir), and Evolution and Genomic Sciences, School of Biological Sciences (W.G.N., E.M.V., D.G.E.), University of Manchester, the NIHR Manchester Biomedical Research Unit (E.F.H.) and the Nightingale Breast Screening Centre, Wythenshawe Hospital (E.F.H., H.I.), Academic Health Science Centre and North West Genomics Laboratory Hub, and the Manchester Centre for Genomic Medicine, St. Mary's Hospital, Manchester University NHS Foundation Trust (W.G.N., E.M.V., D.G.E.), Manchester, the School of Cancer and Pharmaceutical Sciences, Comprehensive Cancer Centre, Guy's Campus, King's College London, London (E.J.S.), the Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham (I.T.), and the Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford (I.T.) - all in the United Kingdom; the Human Genotyping-CEGEN Unit, Human Cancer Genetic Program (A.G.-N., M.R.A., N.Á., B.H., R.N.-T.), and the Human Genetics Group (V.F., A.O., J.B.), Spanish National Cancer Research Center, Centro de Investigación en Red de Enfermedades Raras (A.O., J.B.), Servicio de Oncología Médica, Hospital Universitario La Paz (M.P.Z.), and Molecular Oncology Laboratory, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (M. de la Hoya), Madrid, the Genomic Medicine Group, Galician Foundation of Genomic Medicine, Instituto de Investigación Sanitaria de Santiago de Compostela, Complejo Hospitalario Universitario de Santiago (A. Carracedo, M.G.-D.), and Centro de Investigación en Red de Enfermedades Raras y Centro Nacional de Genotipado, Universidad de Santiago de Compostela (A. Carracedo), Santiago de Compostela, the Oncology and Genetics Unit, Instituto de Investigacion Sanitaria Galicia Sur, Xerencia de Xestion Integrada de Vigo-Servizo Galeo de Saúde, Vigo (J.E.C.), and Servicio de Cirugía General y Especialidades, Hospital Monte Naranco, Oviedo (J.I.A.P.) - all in Spain; the Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund (C. Wahlström, J.V., M.L., T. Törngren, Å.B., A.K.), the Department of Oncology, Örebro University Hospital, Örebro (C. Blomqvist), and the Departments of Medical Epidemiology and Biostatistics (K.C., M.E., M.G., P. Hall, W.H., K.H.), Oncology, Södersjukhuset (P. Hall, S. Margolin), Molecular Medicine and Surgery (A. Lindblom), and Clinical Science and Education, Södersjukhuset (S. Margolin, C. Wendt), Karolinska Institutet, and the Department of Clinical Genetics, Karolinska University Hospital (A. Lindblom), Stockholm - all in Sweden; the Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD (M.T.P., C.F., G.C.-T., A.B.S.), the Cancer Epidemiology Division, Cancer Council Victoria (G.G.G., R.J.M., R.L.M.), the Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health (G.G.G., R.J.M., R.L.M.), and the Department of Clinical Pathology (M.C.S.), University of Melbourne, Anatomical Pathology, Alfred Hospital (C.M.), and the Cancer Epidemiology Division, Cancer Council Victoria (M.C.S.), Melbourne, VIC, and Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC (G.G.G., M.C.S., R.L.M.) - all in Australia; the Division of Molecular Pathology (R.K., S. Cornelissen, M.K.S.), Family Cancer Clinic (F.B.L.H., L.E.K.), Department of Epidemiology (M.A.R.), and Division of Psychosocial Research and Epidemiology (M.K.S.), the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, Division Laboratories, Pharmacy and Biomedical Genetics, Department of Genetics, University Medical Center, Utrecht (M.G.E.M.A.), the Department of Clinical Genetics, Erasmus University Medical Center (J.M.C., A.M.W.O.), and the Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute (B.A.M.H.-G., A. Hollestelle, M.J.H.), Rotterdam, the Department of Clinical Genetics, Maastricht University Medical Center, Maastricht (E.B.G.G.), the Departments of Human Genetics (I.M.M.L., M.P.G.V., P.D.), Clinical Genetics (C.J.A.), and Pathology (P.D.), Leiden University Medical Center, Leiden, the Department of Human Genetics, Radboud University Medical Center, Nijmegen (A.R.M.), and the Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen (J.C.O.) - all in the Netherlands; the Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute (B.D.), and the Division of Cancer Epidemiology and Genetics, National Cancer Institute (T.A., S.J.C., X.R.Y., M.G.-C.), National Institutes of Health, Bethesda, MD; the Department of Pathology, Brigham and Women's Hospital, Harvard Medical School (B.D.), and the Department of Nutrition, Harvard T.H. Chan School of Public Health (R.M.V.D.), Boston; the Departments of Clinical Genetics (K.A.), Oncology (C. Blomqvist), and Obstetrics and Gynecology (H.N., M. Suvanto), Helsinki University Hospital, University of Helsinki, Helsinki, and the Unit of Clinical Oncology, Kuopio University Hospital (P. Auvinen), the Institute of Clinical Medicine, Oncology (P. Auvinen), the Translational Cancer Research Area (J.M.H., V.-M.K., A. Mannermaa), and the Institute of Clinical Medicine, Pathology, and Forensic Medicine (J.M.H., V.-M.K., A. Mannermaa), University of Eastern Finland, and the Biobank of Eastern Finland, Kuopio University Hospital (V.-M.K., A. Mannermaa), Kuopio - both in Finland; the N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus (N.N.A., N.V.B.); the Department of Gynecology and Obstetrics and Institute of Clinical Molecular Biology, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel (N.A.), the Institute of Medical Biometry and Epidemiology (H. Becher) and Cancer Epidemiology Group (T.M., J.C.-C.), University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, the Department of Gynecology and Obstetrics (M.W.B., P.A.F., L.H.) and Institute of Human Genetics (A.B.E.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-European Metropolitan Region of Nuremberg, Erlangen, the Division of Cancer Epidemiology (S.B., A. Jung, P.M.K., J.C.-C.), Molecular Epidemiology Group, C080 (B. Burwinkel, H.S.), Division of Pediatric Neurooncology (A.F.), and Molecular Genetics of Breast Cancer (U.H., M.M., M.U.R., D.T.), German Cancer Research Center, Molecular Biology of Breast Cancer, University Women's Clinic Heidelberg, University of Heidelberg (B. Burwinkel, A.S., H.S.), Hopp Children's Cancer Center (A.F.), Faculty of Medicine, University of Heidelberg (P.M.K.), and National Center for Tumor Diseases, University Hospital and German Cancer Research Center (A.S., C.S.), Heidelberg, the Department of Radiation Oncology (N.V.B., M. Bremer, H.C.) and the Gynecology Research Unit (N.V.B., T.D., P. Hillemanns, T.-W.P.-S., P.S.), Hannover Medical School, Hannover, the Institute of Human Genetics, University of Münster, Münster (N.B.-M.), Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart (H. Brauch, W.-Y.L.), iFIT-Cluster of Excellence, University of Tübingen, and the German Cancer Consortium, German Cancer Research Center, Partner Site Tübingen (H. Brauch), and the University of Tübingen (W.-Y.L.), Tübingen, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum, Bochum (T.B.), Institute for Medical Informatics, Statistics, and Epidemiology, University of Leipzig, Leipzig (C.E.), Center for Hereditary Breast and Ovarian Cancer (E.H., R.K.S.) and Center for Integrated Oncology (E.H., R.K.S.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, the Department of Internal Medicine, Evangelische Kliniken Bonn, Johanniter Krankenhaus, Bonn (Y.-D.K.), the Department of Gynecology and Obstetrics, University of Munich, Campus Großhadern, Munich (A. Meindl), and the Institute of Pathology, Städtisches Klinikum Karlsruhe, Karlsruhe (T.R.) - all in Germany; the Gynecological Cancer Registry, Centre Georges-François Leclerc, Dijon (P. Arveux), and the Center for Research in Epidemiology and Population Health, Team Exposome and Heredity, INSERM, University Paris-Saclay, Villejuif (E.C.-D., P.G., T. Truong) - both in France; the Institute of Biochemistry and Genetics, Ufa Federal Research Center of the Russian Academy of Sciences (M. Bermisheva, E.K.), the Department of Genetics and Fundamental Medicine, Bashkir State University (E.K., D.P., Y.V.), and the Ufa Research Institute of Occupational Health and Human Ecology (Y.V.), Ufa, Russia; the Department of Genetics and Pathology (K.B., A. Jakubowska, J. Lubiński, K.P.) and the Independent Laboratory of Molecular Biology and Genetic Diagnostics (A. Jakubowska), Pomeranian Medical University, Szczecin, Poland; the Copenhagen General Population Study, the Department of Clinical Biochemistry (S.E.B., B.G.N.), and the Department of Breast Surgery (H.F.), Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, and the Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (S.E.B., B.G.N.) - both in Denmark; the Division of Cancer Prevention and Genetics, European Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) (B. Bonanni), the Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (S. Manoukian), the Genome Diagnostics Program, FIRC Institute of Molecular Oncology (P.P.), and the Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (P.R.), Milan; the Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet (A.-L.B.-D., G.I.G.A., V.N.K.), and the Institute of Clinical Medicine, Faculty of Medicine, University of Oslo (A.-L.B.-D., V.N.K.), Oslo; Medical Faculty, Universidad de La Sabana (I.B.), and the Clinical Epidemiology and Biostatistics Department (F.G.) and Institute of Human Genetics (D.T.), Pontificia Universidad Javeriana, Bogota, Colombia; the Department of Internal Medicine and Huntsman Cancer Institute, University of Utah (N.J.C., M.J.M., J.A.W.), and the Intermountain Healthcare Biorepository and Department of Pathology, Intermountain Healthcare (M.H.C.), Salt Lake City; the David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California, Los Angeles (P.A.F.), and Moores Cancer Center (M.G.-D., M.E.M.) and the Department of Family Medicine and Public Health (M.E.M.), University of California San Diego, La Jolla; the Departments of Medical Oncology (V.G., D.M.) and Pathology (M.T.), University Hospital of Heraklion, Heraklion, and the Department of Oncology, University Hospital of Larissa, Larissa (E.S.) - both in Greece; the Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital (G.G., I.L.A.), the Departments of Laboratory Medicine and Pathobiology (A.M.M.) and Molecular Genetics (I.L.A.), University of Toronto, and the Laboratory Medicine Program, University Health Network (A.M.M.), Toronto, and the Genomics Center, Centre Hospitalier Universitaire de Québec-Université Laval Research Center, Québec City, QC (J.S.) - both in Canada; the Department of Electron Microscopy and Molecular Pathology (A. Hadjisavvas, K.K., M.A.L.), the Cyprus School of Molecular Medicine (A. Hadjisavvas, K.K., M.A.L., K. Michailidou), and the Biostatistics Unit (K. Michailidou), Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus; the Saw Swee Hock School of Public Health (M. Hartman, R.M.V.D.) and the Department of Medicine, Yong Loo Lin School of Medicine (R.M.V.D.), National University of Singapore, the Department of Surgery, National University Health System (M. Hartman, J. Li), and the Human Genetics Division, Genome Institute of Singapore (J. Li), Singapore; the Department of Mathematical Sciences, Faculty of Science and Engineering, University of Nottingham Malaysia (W.K.H.), and the Breast Cancer Research Programme, Cancer Research Malaysia (W.K.H., P.S.N., S.-Y.Y., S.H.T.), Selangor, and the Breast Cancer Research Unit, Cancer Research Institute (N.A.M.T.), and the Department of Surgery, Faculty of Medicine (N.A.M.T., P.S.N., S.H.T.), University Malaya, Kuala Lumpur - both in Malaysia; Surgery, School of Medicine, National University of Ireland, Galway (M.J.K., N. Miller); the Department of Surgery, Daerim Saint Mary's Hospital (S.-W.K.), the Department of Surgery, Ulsan University College of Medicine and Asan Medical Center (J.W.L.), the Department of Surgery, Soonchunhyang University College of Medicine and Soonchunhyang University Hospital (M.H.L.), Integrated Major in Innovative Medical Science, Seoul National University College of Medicine (S.K.P.), and the Cancer Research Institute, Seoul National University (S.K.P.), Seoul, South Korea; the Department of Basic Sciences, Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, Pakistan (M.U.R.); and the National Cancer Institute, Ministry of Public Health, Nonthaburi, Thailand (S.T.).
Background: Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking.
Methods: We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes.
Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk.
Am J Hum Genet
November 2020
The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Molecular Pathology, Amsterdam 1066 CX, the Netherlands; The Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Division of Psychosocial Research and Epidemiology, Amsterdam 1066 CX, the Netherlands. Electronic address:
Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium.
View Article and Find Full Text PDFAssociation of germline variation with the survival of women with pathogenic variants and breast cancer.
NPJ Breast Cancer
September 2020
University of Helsinki, Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki, Finland.
Germline genetic variation has been suggested to influence the survival of breast cancer patients independently of tumor pathology. We have studied survival associations of genetic variants in two etiologically unique groups of breast cancer patients, the carriers of germline pathogenic variants in or genes. We found that rs57025206 was significantly associated with the overall survival, predicting higher mortality of carrier patients with estrogen receptor-negative breast cancer, with a hazard ratio 4.
View Article and Find Full Text PDFBayesian copy number detection and association in large-scale studies.
BMC Cancer
September 2020
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Background: Germline copy number variants (CNVs) increase risk for many diseases, yet detection of CNVs and quantifying their contribution to disease risk in large-scale studies is challenging due to biological and technical sources of heterogeneity that vary across the genome within and between samples.
Methods: We developed an approach called CNPBayes to identify latent batch effects in genome-wide association studies involving copy number, to provide probabilistic estimates of integer copy number across the estimated batches, and to fully integrate the copy number uncertainty in the association model for disease.
Results: Applying a hidden Markov model (HMM) to identify CNVs in a large multi-site Pancreatic Cancer Case Control study (PanC4) of 7598 participants, we found CNV inference was highly sensitive to technical noise that varied appreciably among participants.
Ancestral roles of atypical cadherins in planar cell polarity.
Proc Natl Acad Sci U S A
August 2020
Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Sinai Health System, Toronto, ON M5G 1X5, Canada;
Fat, Fat-like, and Dachsous family cadherins are giant proteins that regulate planar cell polarity (PCP) and cell adhesion in bilaterians. Their evolutionary origin can be traced back to prebilaterian species, but their ancestral function(s) are unknown. We identified Fat-like and Dachsous cadherins in , a member of phylum Cnidaria a sister group of bilaterian.
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