Search

Your search keyword '"Yang, Xin [0000-0003-0037-3790]"' showing total 3 results
Start Over Author "Yang, Xin [0000-0003-0037-3790]" Language undetermined
3 results on '"Yang, Xin [0000-0003-0037-3790]"'

1. Prospective validation of the BOADICEA multifactorial breast cancer risk prediction model in a large prospective cohort study

Author

Xin Yang, Mikael Eriksson, Kamila Czene, Andrew Lee, Goska Leslie, Michael Lush, Jean Wang, Joe Dennis, Leila Dorling, Sara Carvalho, Nasim Mavaddat, Jacques Simard, Marjanka K Schmidt, Douglas F Easton, Per Hall, Antonis C Antoniou, Yang, Xin [0000-0003-0037-3790], Lee, Andrew [0000-0003-0677-0252], Antoniou, Antonis C [0000-0001-9223-3116], and Apollo - University of Cambridge Repository

Subjects
genetic counseling, public health, Genes, BRCA2, Genetics, Humans, Female, Breast Neoplasms, Genetic Predisposition to Disease, Prospective Studies, Middle Aged, women's health, Risk Assessment, Genetics (clinical)
Abstract

Peer reviewed: True, Acknowledgements: We would like to thank all the participants, clinicians and other healthcare professionals who have contributed to the KARMA cohort., Funder: CHU de Quebec, Funder: NIHR Cambridge Biomedical Research Centre, Funder: Quebec Breast Cancer Foundation, Funder: Ontario Research Fund, Funder: the Märit and Hans Rausing’s Initiative Against Breast Cancer, BACKGROUND: The multifactorial Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) breast cancer risk prediction model has been recently extended to consider all established breast cancer risk factors. We assessed the clinical validity of the model in a large independent prospective cohort. METHODS: We validated BOADICEA (V.6) in the Swedish KARolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA) cohort including 66 415 women of European ancestry (median age 54 years, IQR 45-63; 816 incident breast cancers) without previous cancer diagnosis. We calculated 5-year risks on the basis of questionnaire-based risk factors, pedigree-structured first-degree family history, mammographic density (BI-RADS), a validated breast cancer polygenic risk score (PRS) based on 313-SNPs, and pathogenic variant status in 8 breast cancer susceptibility genes: BRCA1, BRCA2, PALB2, CHEK2, ATM, RAD51C, RAD51D and BARD1. Calibration was assessed by comparing observed and expected risks in deciles of predicted risk and the calibration slope. The discriminatory ability was assessed using the area under the curve (AUC). RESULTS: Among the individual model components, the PRS contributed most to breast cancer risk stratification. BOADICEA was well calibrated in predicting the risks for low-risk and high-risk women when all, or subsets of risk factors are included in the risk prediction. Discrimination was maximised when all risk factors are considered (AUC=0.70, 95% CI: 0.66 to 0.73; expected-to-observed ratio=0.88, 95% CI: 0.75 to 1.04; calibration slope=0.97, 95% CI: 0.95 to 0.99). The full multifactorial model classified 3.6% women as high risk (5-year risk ≥3%) and 11.1% as very low risk (5-year risk

Published
2022
Full Text
View/download PDF

2. Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Author

Barnes, Daniel R, Silvestri, Valentina, Leslie, Goska, McGuffog, Lesley, Dennis, Joe, Yang, Xin, Adlard, Julian, Agnarsson, Bjarni A, Ahmed, Munaza, Aittomäki, Kristiina, Andrulis, Irene L, Arason, Adalgeir, Arnold, Norbert, Auber, Bernd, Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa B, Barrowdale, Daniel, Barwell, Julian, Belotti, Muriel, Benitez, Javier, Berthet, Pascaline, Boonen, Susanne E, Borg, Åke, Bozsik, Aniko, Brady, Angela F, Brennan, Paul, Brewer, Carole, Brunet, Joan, Bucalo, Agostino, Buys, Saundra S, Caldés, Trinidad, Caligo, Maria A, Campbell, Ian, Cassingham, Hayley, Christensen, Lise Lotte, Cini, Giulia, Claes, Kathleen BM, GEMO Study Collaborators, EMBRACE Collaborators, Cook, Jackie, Coppa, Anna, Cortesi, Laura, Damante, Giuseppe, Darder, Esther, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Putter, Robin, Del Valle, Jesús, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M, Donaldson, Alan, Eason, Jacqueline, Eeles, Ros, Engel, Christoph, Evans, D Gareth, Feliubadaló, Lidia, Fostira, Florentia, Frone, Megan, Frost, Debra, Gallagher, David, Gehrig, Andrea, Giraud, Sophie, Glendon, Gord, Godwin, Andrew K, Goldgar, David E, Greene, Mark H, Gregory, Helen, Gross, Eva, Hahnen, Eric, Hamann, Ute, Hansen, Thomas VO, Hanson, Helen, Hentschel, Julia, Horvath, Judit, KConFab Investigators, HEBON Investigators, Izatt, Louise, Izquierdo, Angel, James, Paul A, Janavicius, Ramunas, Jensen, Uffe Birk, Johannsson, Oskar Th, John, Esther M, Kramer, Gero, Kroeldrup, Lone, Kruse, Torben A, Lautrup, Charlotte, Lazaro, Conxi, Lesueur, Fabienne, Lopez-Fernández, Adria, Mai, Phuong L, Manoukian, Siranoush, Matrai, Zoltan, Matricardi, Laura, Maxwell, Kara N, Mebirouk, Noura, Meindl, Alfons, Montagna, Marco, Monteiro, Alvaro N, Morrison, Patrick J, Muranen, Taru A, Murray, Alex, Nathanson, Katherine L, Neuhausen, Susan L, Nevanlinna, Heli, Nguyen-Dumont, Tu, Niederacher, Dieter, Olah, Edith, Olopade, Olufunmilayo I, Palli, Domenico, Parsons, Michael T, Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Peterlongo, Paolo, Petersen, Annabeth H, Pinto, Pedro, Porteous, Mary E, Pottinger, Caroline, Pujana, Miquel Angel, Radice, Paolo, Ramser, Juliane, Rantala, Johanna, Robson, Mark, Rogers, Mark T, Rønlund, Karina, Rump, Andreas, Sánchez de Abajo, Ana María, Shah, Payal D, Sharif, Saba, Side, Lucy E, Singer, Christian F, Stadler, Zsofia, Steele, Linda, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen Yen, Teixeira, Manuel R, Teulé, Alex, Thull, Darcy L, Tischkowitz, Marc, Toland, Amanda E, Tommasi, Stefania, Toss, Angela, Trainer, Alison H, Tripathi, Vishakha, Valentini, Virginia, van Asperen, Christi J, Venturelli, Marta, Viel, Alessandra, Vijai, Joseph, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Whaite, Anna, Zanna, Ines, Offit, Kenneth, Thomassen, Mads, Couch, Fergus J, Schmutzler, Rita K, Simard, Jacques, Easton, Douglas F, Chenevix-Trench, Georgia, Antoniou, Antonis C, Ottini, Laura, Consortium of Investigators of Modifiers of BRCA1 and BRCA2, Barnes, Daniel R [0000-0002-3781-7570], Silvestri, Valentina [0000-0003-0712-9379], Leslie, Goska [0000-0001-5756-6222], Dennis, Joe [0000-0003-4591-1214], Yang, Xin [0000-0003-0037-3790], Adlard, Julian [0000-0002-1693-0435], Agnarsson, Bjarni A [0000-0001-7721-9965], Andrulis, Irene L [0000-0002-4226-6435], Arason, Adalgeir [0000-0003-0480-886X], Arnold, Norbert [0000-0003-4523-8808], Auber, Bernd [0000-0003-1880-291X], Azzollini, Jacopo [0000-0002-9364-9778], Barkardottir, Rosa B [0000-0003-0629-2772], Barrowdale, Daniel [0000-0003-1661-3939], Benitez, Javier [0000-0002-0923-7202], Boonen, Susanne E [0000-0002-7824-2080], Bozsik, Aniko [0000-0001-5410-9173], Brennan, Paul [0000-0003-1128-6254], Brunet, Joan [0000-0003-1945-3512], Bucalo, Agostino [0000-0003-3475-1067], Caligo, Maria A [0000-0003-0589-1829], Campbell, Ian [0000-0002-7773-4155], Cassingham, Hayley [0000-0001-9922-2321], Cini, Giulia [0000-0002-8696-8922], Claes, Kathleen BM [0000-0003-0841-7372], Coppa, Anna [0000-0001-9758-5444], Cortesi, Laura [0000-0001-8950-8561], Darder, Esther [0000-0002-7764-1397], de la Hoya, Miguel [0000-0002-8113-1410], de Putter, Robin [0000-0001-9410-8941], Del Valle, Jesús [0000-0003-3607-7045], Domchek, Susan M [0000-0002-5914-7272], Donaldson, Alan [0000-0001-9193-4172], Eason, Jacqueline [0000-0002-8711-8671], Engel, Christoph [0000-0002-7247-282X], Fostira, Florentia [0000-0003-2751-2332], Frone, Megan [0000-0001-8273-8866], Glendon, Gord [0000-0001-8630-6673], Godwin, Andrew K [0000-0002-3987-9580], Greene, Mark H [0000-0003-1852-9239], Hahnen, Eric [0000-0003-2448-7872], Hanson, Helen [0000-0002-3303-8713], Izatt, Louise [0000-0003-1258-4843], Izquierdo, Angel [0000-0003-2004-3246], James, Paul A [0000-0002-4361-4657], John, Esther M [0000-0003-3259-8003], Kroeldrup, Lone [0000-0003-3623-6536], Kruse, Torben A [0000-0002-2460-6483], Lazaro, Conxi [0000-0002-7198-5906], Lesueur, Fabienne [0000-0001-7404-4549], Matrai, Zoltan [0000-0001-8160-7100], Montagna, Marco [0000-0002-4929-2150], Monteiro, Alvaro N [0000-0002-8448-4801], Morrison, Patrick J [0000-0002-2823-1762], Muranen, Taru A [0000-0002-5895-1808], Nathanson, Katherine L [0000-0002-6740-0901], Neuhausen, Susan L [0000-0001-5053-0390], Nevanlinna, Heli [0000-0002-0916-2976], Nguyen-Dumont, Tu [0000-0002-6217-0182], Niederacher, Dieter [0000-0001-6231-9226], Palli, Domenico [0000-0002-5558-2437], Parsons, Michael T [0000-0003-3242-8477], Perez-Segura, Pedro [0000-0001-5049-7199], Peterlongo, Paolo [0000-0001-6951-6855], Pinto, Pedro [0000-0001-6289-5792], Pottinger, Caroline [0000-0003-4233-882X], Radice, Paolo [0000-0001-6298-4111], Robson, Mark [0000-0002-3109-1692], Rump, Andreas [0000-0001-7116-6364], Sharif, Saba [0000-0002-9564-4890], Steele, Linda [0000-0003-3628-2022], Stoppa-Lyonnet, Dominique [0000-0002-5438-8309], Teixeira, Manuel R [0000-0002-4896-5982], Thull, Darcy L [0000-0001-7999-2804], Tischkowitz, Marc [0000-0002-7880-0628], Toland, Amanda E [0000-0002-0271-1792], Tommasi, Stefania [0000-0002-2157-2978], Toss, Angela [0000-0002-1854-6701], Tripathi, Vishakha [0000-0001-8118-8364], Valentini, Virginia [0000-0003-3393-7185], van Asperen, Christi J [0000-0002-1436-7650], Venturelli, Marta [0000-0003-0658-8004], Viel, Alessandra [0000-0003-2804-0840], Vijai, Joseph [0000-0002-7933-151X], Whaite, Anna [0000-0003-4485-0341], Simard, Jacques [0000-0001-6906-3390], Easton, Douglas F [0000-0003-2444-3247], Chenevix-Trench, Georgia [0000-0002-1878-2587], Ottini, Laura [0000-0001-8030-0449], and Apollo - University of Cambridge Repository

Subjects
Aged, 80 and over, BRCA2 Protein, Male, Heterozygote, BRCA1 Protein, Prostatic Neoplasms, Breast Neoplasms, Polymorphism, Single Nucleotide, Risk Assessment, Risk Factors, Mutation, Humans, Genetic Predisposition to Disease, skin and connective tissue diseases
Abstract

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). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. RESULTS: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. CONCLUSIONS: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.

Published
2022

3. Comprehensive epithelial tubo-ovarian cancer risk prediction model incorporating genetic and epidemiological risk factors

Author

Stephanie Archer, Simon A. Gayther, Jatinder Kalsi, Usha Menon, Faiza Gaba, Andy C. H. Lee, Tim Carver, Fiona M Walter, Paul D.P. Pharoah, Antonis C. Antoniou, Marc Tischkowitz, Ian Jacobs, Ranjit Manchanda, Douglas F. Easton, Xin Yang, Jonathan Tyrer, Aleksandra Gentry-Maharaj, Goska Leslie, Andy Ryan, Susan J. Ramus, Alex P Cunningham, Nasim Mavaddat, Lee, Andrew [0000-0003-0677-0252], Yang, Xin [0000-0003-0037-3790], Tyrer, Jonathan [0000-0003-3724-4757], Mavaddat, Nasim [0000-0003-0307-055X], Cunningham, Alex [0000-0002-3737-9611], Archer, Stephanie [0000-0003-1349-7178], Manchanda, Ranjit [0000-0003-3381-5057], Ramus, Susan J [0000-0003-0005-7798], Tischkowitz, Marc [0000-0002-7880-0628], Easton, Douglas [0000-0003-2444-3247], Pharoah, Paul [0000-0001-8494-732X], Antoniou, Antonis [0000-0001-9223-3116], Apollo - University of Cambridge Repository, and Antoniou, Antonis C [0000-0001-9223-3116]

Subjects
Oncology, medicine.medical_specialty, Percentile, Multifactorial Inheritance, Tubo-ovarian, endocrine system diseases, Genetic counseling, Population, Breast Neoplasms, Carcinoma, Ovarian Epithelial, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Epidemiology, Medicine, Humans, Genetic Predisposition to Disease, genetics, Family history, education, Adverse effect, Cancer genetics, Genetics (clinical), 030304 developmental biology, Ovarian Neoplasms, clinical decision-making, 0303 health sciences, education.field_of_study, genetic counseling, business.industry, public health, Cancer, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, Female, business, early diagnosis
Abstract

Funder: Department of Health; FundRef: http://dx.doi.org/10.13039/501100000276, Funder: Ontario Research Fund, Funder: CHU de Quebec Foundation, Funder: Fondation du cancer du sein du Qu��bec; FundRef: http://dx.doi.org/10.13039/100016328, Funder: The Eve Appeal, Background: Epithelial tubo-ovarian cancer (EOC) has high mortality partly due to late diagnosis. Prevention is available but may be associated with adverse effects. A multifactorial risk model based on known genetic and epidemiological risk factors (RFs) for EOC can help identify women at higher risk who could benefit from targeted screening and prevention. Methods: We developed a multifactorial EOC risk model for women of European ancestry incorporating the effects of pathogenic variants (PVs) in BRCA1, BRCA2, RAD51C, RAD51D and BRIP1, a Polygenic Risk Score (PRS) of arbitrary size, the effects of RFs and explicit family history (FH) using a synthetic model approach. The PRS, PV and RFs were assumed to act multiplicatively. Results: Based on a currently available PRS for EOC that explains 5% of the EOC polygenic variance, the estimated lifetime risks under the multifactorial model in the general population vary from 0.5% to 4.6% for the first to 99th percentiles of the EOC risk distribution. The corresponding range for women with an affected first-degree relative is 1.9%���10.3%. Based on the combined risk distribution, 33% of RAD51D PV carriers are expected to have a lifetime EOC risk of less than 10%. RFs provided the widest distribution, followed by the PRS. In an independent partial model validation, absolute and relative 5-year risks were well calibrated in quintiles of predicted risk. Conclusion: This multifactorial risk model can facilitate stratification, in particular among women with FH of cancer and/or moderate-risk and high-risk PVs. The model is available via the CanRisk Tool (www.canrisk.org).

Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results