181 results match your criteria: "Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital[Affiliation]"
Hormonal Contraception and Breast Cancer Risk for Carriers of Germline Mutations in and .
J Clin Oncol
October 2024
Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
Article Synopsis
- The study investigates the relationship between hormonal contraceptive use and breast cancer risk in both unaffected women and mutation carriers.
- Out of the participants, it was found that hormonal contraceptive use was linked to a higher breast cancer risk in mutation carriers, particularly with longer duration of use.
- The findings suggest that decisions regarding hormonal contraceptive use for women with genetic mutations should consider individual risk factors and benefits.
Analysis of more than 400,000 women provides case-control evidence for and variant classification.
medRxiv
September 2024
Biostatistics Unit, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus.
Article Synopsis
- Clinical genetic testing helps find cancer risks by identifying gene changes, but some of these changes are confusing because we don't know what they mean (called VUS).
- Researchers studied a huge number of breast cancer patients and healthy people to understand these confusing gene changes better.
- They found that their method of analyzing data closely matches what other experts say about which gene changes are harmless or harmful, giving more information about 785 unclear changes.
Co-observation of germline pathogenic variants in breast cancer predisposition genes: Results from analysis of the BRIDGES sequencing dataset.
Am J Hum Genet
September 2024
Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia; Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address:
Article Synopsis
- * Analysis of data from over 55,000 breast cancer patients showed that co-observation of variants in BRCA1, BRCA2, and PALB2 with other breast cancer genes occurred less frequently than expected, suggesting a potential correlation with pathogenicity.
- * The findings indicate that identifying a variant of uncertain significance alongside a known pathogenic variant supports evidence against the variant's pathogenicity, which could improve variant classification in clinical settings and for other genetic conditions.
Publisher Correction: Understanding the genetic complexity of puberty timing across the allele frequency spectrum.
Nat Genet
August 2024
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
Understanding the genetic complexity of puberty timing across the allele frequency spectrum.
Nat Genet
July 2024
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
Article Synopsis
- Scientists looked at the timing of when girls start their periods (called menarche) and how it can affect their health later in life.
- They studied about 800,000 women and found over a thousand genetic signals that influence when menstruation starts.
- Some women have a much higher chance of starting their periods too early or too late based on their genetic makeup, suggesting that genes play a big role in this process!
Disentangling the relationships of body mass index and circulating sex hormone concentrations in mammographic density using Mendelian randomization.
Breast Cancer Res Treat
July 2024
Department of Epidemiology, University of Washington, Seattle, WA, USA.
Purpose: Mammographic density phenotypes, adjusted for age and body mass index (BMI), are strong predictors of breast cancer risk. BMI is associated with mammographic density measures, but the role of circulating sex hormone concentrations is less clear. We investigated the relationship between BMI, circulating sex hormone concentrations, and mammographic density phenotypes using Mendelian randomization (MR).
View Article and Find Full Text PDFDifferences in polygenic score distributions in European ancestry populations: implications for breast cancer risk prediction.
medRxiv
February 2024
Biostatistics Unit, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus, 2371.
The 313-variant polygenic risk score (PRS) provides a promising tool for breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed. Here, we explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 225,105 female participants from the UK Biobank.
View Article and Find Full Text PDFChildhood physical activity and pubertal timing: findings from the LEGACY girls study.
Int J Epidemiol
February 2024
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
Background: There is limited research on whether physical activity (PA) in early childhood is associated with the timing of pubertal events in girls.
Methods: We used data collected over 2011-16 from the LEGACY Girls Study (n = 984; primarily aged 6-13 years at study enrolment), a multicentre North American cohort enriched for girls with a breast cancer family history (BCFH), to evaluate if PA is associated with age at thelarche, pubarche and menarche. Maternal-reported questionnaire data measured puberty outcomes, PA in early childhood (ages 3-5 years) and total metabolic equivalents of organized PA in middle childhood (ages 7-9 years).
Polymorphisms in genes of melatonin biosynthesis and signaling support the light-at-night hypothesis for breast cancer.
Eur J Epidemiol
October 2023
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
Article Synopsis
- Light-at-night exposure is linked to decreased melatonin production from the pineal gland and is considered a potential risk factor for breast cancer by the IARC.
- A study of 44,405 women examined the relationship between breast cancer risk and genetic variations (SNPs) associated with melatonin synthesis and signaling, using logistic regression for analysis.
- Significant findings included 10 SNPs in the TPH2 gene and one in the MAPK8 gene, suggesting that these genetic factors may influence breast cancer risk, particularly in relation to circadian disruptions caused by light exposure at night.
A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry.
Breast Cancer Res
August 2023
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Article Synopsis
- A genome-wide study explored gene-environment interactions (G×E) to identify variants that could impact breast cancer risk, analyzing data from around 72,285 breast cancer cases and 80,354 controls.
- Researchers found two specific SNP-risk factor pairs that showed a significant association with breast cancer risk, including variations related to adult height and age at menarche.
- Overall, the study concluded that G×E interactions contribute minimally to the heritability of breast cancer and don't significantly enhance risk prediction for the disease.
Understanding the genetic complexity of puberty timing across the allele frequency spectrum.
medRxiv
June 2023
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
Pubertal timing varies considerably and has been associated with a range of health outcomes in later life. To elucidate the underlying biological mechanisms, we performed multi-ancestry genetic analyses in ~800,000 women, identifying 1,080 independent signals associated with age at menarche. Collectively these loci explained 11% of the trait variance in an independent sample, with women at the top and bottom 1% of polygenic risk exhibiting a ~11 and ~14-fold higher risk of delayed and precocious pubertal development, respectively.
View Article and Find Full Text PDFEvaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel.
J Med Genet
November 2023
Department of Human Molecular Genetics and Biochemistry, Tel Aviv University, Tel Aviv, Israel
Article Synopsis
- Polygenic risk scores (PRSs), derived from genome-wide association studies (GWASs), can enhance breast cancer risk evaluation but are primarily based on European populations.
- This study analyzed the effectiveness of European-based PRS models in identifying breast cancer risk among Ashkenazi Jewish women in Israel using data from two cohorts.
- Results indicated that these PRS models successfully identified Ashkenazi Jewish women at high risk for breast cancer, suggesting they could improve risk assessment in this group.
Spectrum and Frequency of Germline Protein-Truncating Variants in 44,803 European Female Breast Cancer Cases.
Cancers (Basel)
June 2023
Genome Diagnostics Program, IFOM ETS-The AIRC Institute of Molecular Oncology, 20139 Milan, Italy.
Article Synopsis
- * The study revealed significant variation in the prevalence of four common PTVs across different regions in Europe, with p.Gln1701* being most common in Northern Europe and p.Gly1906Alafs*12 most common in Southern Europe.
- * Findings suggest that the distribution of rare PTVs is more heterogeneous in Southwestern and Central Europe compared to Northeastern Europe, which will aid in crafting targeted genetic testing for breast cancer in specific European populations.
Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival.
Cancer Med
August 2023
Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
Article Synopsis
- Breast cancer patients with the CHEK2 c.1100delC variant have a heightened risk of developing a second breast cancer (contralateral breast cancer) and generally experience worse survival outcomes compared to those without the variant.
- A study involving over 82,000 women aimed to evaluate how the CHEK2 variant, radiotherapy, and systemic treatments affect the risk of contralateral breast cancer and breast cancer-specific survival.
- Findings indicated that while systemic therapy (especially the combination of chemotherapy and endocrine therapy) lowers the risk of contralateral breast cancer, CHEK2 c.1100delC carriers still faced poorer survival rates, suggesting other factors at play beyond the risk of developing a second cancer.*
Associations of height, body mass index, and weight gain with breast cancer risk in carriers of a pathogenic variant in BRCA1 or BRCA2: the BRCA1 and BRCA2 Cohort Consortium.
Breast Cancer Res
June 2023
Institute for Medical Informatics, Statistics and Epidemiology, Leipzig University, Leipzig, Germany.
Article Synopsis
- The study examines the relationship between height, BMI, and weight gain with breast cancer risk in women who carry BRCA1 or BRCA2 gene variants, unlike previous research that focused on the general population.
- An analysis of 8,091 BRCA1/2 variant carriers found that taller height increases the risk of premenopausal breast cancer for BRCA2 carriers, while higher BMI in young adulthood is linked to lower risk for both BRCA1 and BRCA2 carriers.
- The findings suggest that higher BMI and weight gain are related to increased postmenopausal breast cancer risk for BRCA1 carriers, indicating that body measurements impact breast cancer risk similarly in these variant carriers as
PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants.
NPJ Breast Cancer
May 2023
Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Article Synopsis
- A study evaluated the PREDICT v 2.2 tool for predicting the prognosis of breast cancer in patients with BRCA1 and BRCA2 gene variants, using data from over 5,400 carriers across two major cancer research consortia.
- The PREDICT model showed reasonable effectiveness in distinguishing high-mortality groups for estrogen receptor (ER)-negative breast cancer in BRCA1 carriers, while for BRCA2 carriers, its accuracy was lower and fluctuated based on tumor characteristics.
- The findings suggest that while PREDICT can aid in management of breast cancer patients, adjustments for BRCA2 status and tumor features are necessary to improve prognosis estimates, particularly for ER-positive cases.
Ovarian cancer pathology characteristics as predictors of variant pathogenicity in BRCA1 and BRCA2.
Br J Cancer
June 2023
Biostatistics Unit, The Cyprus Institute of Neurology and Genetics, Nicosia, 2371, Cyprus.
Background: The distribution of ovarian tumour characteristics differs between germline BRCA1 and BRCA2 pathogenic variant carriers and non-carriers. In this study, we assessed the utility of ovarian tumour characteristics as predictors of BRCA1 and BRCA2 variant pathogenicity, for application using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) variant classification system.
Methods: Data for 10,373 ovarian cancer cases, including carriers and non-carriers of BRCA1 or BRCA2 pathogenic variants, were collected from unpublished international cohorts and consortia and published studies.
The impact of coding germline variants on contralateral breast cancer risk and survival.
Am J Hum Genet
March 2023
The Netherlands Cancer Institute, Division of Molecular Pathology, Plesmanlaan 121, 1066 Amsterdam, the Netherlands; The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Psychosocial Research and Epidemiology, Amsterdam, the Netherlands. Electronic address:
Article Synopsis
- - The study investigated the links between genetic variants in breast cancer susceptibility genes (besides BRCA1, BRCA2, and CHEK2) and risks of developing contralateral breast cancer (CBC) and breast cancer-specific survival (BCSS) in 34,401 women of European ancestry who had been diagnosed with breast cancer.
- - Significant findings revealed that protein-truncating variants (PTVs) and certain missense variants (MSVs) in genes like BRCA1, BRCA2, TP53, CHEK2, and PALB2 were associated with higher CBC risk and negative impacts on BCSS, indicating that these genetic factors play a crucial role in cancer outcomes.
- - The results showed minimal
FANCM missense variants and breast cancer risk: a case-control association study of 75,156 European women.
Eur J Hum Genet
May 2023
IFOM ETS - The AIRC Institute of Molecular Oncology, Genome Diagnostics Program, Milan, Italy.
Evidence from literature, including the BRIDGES study, indicates that germline protein truncating variants (PTVs) in FANCM confer moderately increased risk of ER-negative and triple-negative breast cancer (TNBC), especially for women with a family history of the disease. Association between FANCM missense variants (MVs) and breast cancer risk has been postulated. In this study, we further used the BRIDGES study to test 689 FANCM MVs for association with breast cancer risk, overall and in ER-negative and TNBC subtypes, in 39,885 cases (7566 selected for family history) and 35,271 controls of European ancestry.
View Article and Find Full Text PDFAggregation tests identify new gene associations with breast cancer in populations with diverse ancestry.
Genome Med
January 2023
Division of Psychiatry, University College London, London, UK.
Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.
Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls.
Associations of a Breast Cancer Polygenic Risk Score With Tumor Characteristics and Survival.
J Clin Oncol
April 2023
Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Article Synopsis
- A polygenic risk score (PRS) made up of 313 genetic variants is linked to breast cancer and its recurrence, prompting this study to explore its relationship with tumor characteristics and survival rates in breast cancer patients.
- The research involved nearly 100,000 women of European ancestry and around 13,000 of Asian ancestry, analyzing data through logistic and Cox regression to evaluate the association between PRS and factors like tumor grade and hormone receptor status.
- While higher PRS was related to better tumor features and initially appeared to correlate with improved overall and breast cancer-specific survival, these associations diminished after accounting for other clinical factors, suggesting PRS isn't useful for clinical management upon diagnosis.
A likelihood ratio approach for utilizing case-control data in the clinical classification of rare sequence variants: application to and .
Hum Mutat
May 2024
Biostatistics Unit, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
Article Synopsis
- Many variants found in disease susceptibility genes are classified as variants of uncertain significance (VUS), making their interpretation critical for clinical decisions.
- This study introduces a new likelihood ratio-based method that takes into account gene-specific age-related penetrance to better analyze the pathogenicity of these variants.
- The method outperformed traditional approaches in simulated and real datasets, allowing for clearer classifications of variants as pathogenic or non-pathogenic for conditions like breast cancer, and includes user-friendly tools for researchers.
Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study.
Br J Sports Med
October 2022
Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia
Article Synopsis
- - The study investigates the causal relationship between physical activity, sedentary behavior, and breast cancer risk using Mendelian randomization, analyzing data from over 130,000 European women.
- - Findings suggest that higher levels of genetic predisposition to physical activity are linked to a significantly lower overall breast cancer risk, particularly for pre/perimenopausal cases, while increased sedentary time correlates with a higher risk of certain types of tumors.
- - The results are consistent across various test groups and indicate that promoting physical activity and reducing sedentary behavior might be beneficial in mitigating breast cancer risks.
Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers.
Commun Biol
October 2022
Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand.
The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation.
View Article and Find Full Text PDFIncorporating progesterone receptor expression into the PREDICT breast prognostic model.
Eur J Cancer
September 2022
University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Oncology, Cambridge, CB1 8RN, UK; University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, CB1 8RN, UK.
Background: Predict Breast (www.predict.nhs.
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