Douglas Easton
University of Cambridge
H-index: 208
Europe-United Kingdom
Description
Douglas Easton, With an exceptional h-index of 208 and a recent h-index of 114 (since 2020), a distinguished researcher at University of Cambridge, specializes in the field of Genetic Epidemiology, Cancer Epidemiology, Statistical Genetics.
His recent articles reflect a diverse array of research interests and contributions to the field:
Validation of the BOADICEA Model in a Prospective cohort of BRCA1/2 Pathogenic Variant Carriers
Disentangling the relationships of body mass index and circulating sex hormone concentrations in mammographic density using Mendelian randomization
Differences in polygenic score distributions in European ancestry populations: implications for breast cancer risk prediction
Age-specific breast and ovarian cancer risks associated with germline BRCA1 or BRCA2 pathogenic variants–an Asian study of 572 families
Systematic Minigene-Based Splicing Analysis and Tentative Clinical Classification of 52 CHEK2 Splice-Site Variants
Abstract IA18: Genetic susceptibility to breast cancer: Recent advances and application to personalised prevention
Novel breast cancer susceptibility loci under linkage peaks identified in African ancestry consortia
Estimation of age of onset and progression of breast cancer by absolute risk dependent on polygenic risk score and other risk factors
Professor Information
University | University of Cambridge |
---|---|
Position | Professor of Genetic Epidemiology |
Citations(all) | 199884 |
Citations(since 2020) | 60354 |
Cited By | 165335 |
hIndex(all) | 208 |
hIndex(since 2020) | 114 |
i10Index(all) | 933 |
i10Index(since 2020) | 666 |
University Profile Page | University of Cambridge |
Research & Interests List
Genetic Epidemiology
Cancer Epidemiology
Statistical Genetics
Top articles of Douglas Easton
Validation of the BOADICEA Model in a Prospective cohort of BRCA1/2 Pathogenic Variant Carriers
Background No validation has been conducted for the BOADICEA multifactorial breast cancer risk prediction model specifically in BRCA1/2 pathogenic variant (PV) carriers to date. Here, we evaluated the performance of BOADICEA in predicting five-year breast cancer risks in a prospective cohort of BRCA1/2 PV carriers ascertained through clinical genetic centres. Methods We evaluated the model calibration and discriminatory ability in the prospective TRANsIBCCS cohort study comprising 1,614 BRCA1 and 1,365 BRCA2 PV carriers (209 incident cases). Study participants had lifestyle, reproductive, hormonal, anthropometric risk factor information, a polygenic risk score based on 313 single nucleotide polymorphisms, and family history information. Results The full multifactorial model considering family history together with all other risk factors was well calibrated overall (E/O=1.07, 95%CI:0.92-1.24) and in quintiles of predicted risk. Discrimination was maximized when all risk factors were considered (Harrell's C-index=0.70, 95%CI:0.67-0.74; AUC=0.79, 95%CI:0.76-0.82). The model performance was similar when evaluated separately in BRCA1 or BRCA2 PV carriers. The full model identified 5.8%, 12.9% and 24.0% of BRCA1/2 PV carriers with five-year breast cancer risks of <1.65%, <3% and <5% respectively, risk thresholds commonly used for different management and risk-reduction options. Conclusion BOADICEA may be used to aid personalised cancer risk management and decision making for BRCA1 and BRCA2 PV carriers. It is implemented in the free-access CanRisk tool (www.canrisk.org).
Authors
Xin Yang,Thea Mooij,Goska Leslie,Lorenzo Ficorella,Nadine Andrieu,Karin Kast,Christian Singer,Anna Jakubowska,Carla Gils,Yen Tan,Christoph Engel,Muriel Adank,Christi Asperen,Margreet Ausems,Pascaline Berthet,EMBRACE collaborators,Margriet Collee,Jackie Cook,Jacqueline Eason,Karin Spaendonck-Zwarts,Gareth Evans,Encarna Garcia,Helen Hanson,Louise Izatt,Zoe Kemp,Fiona Lalloo,Christine Lasset,Fabienne Lesueur,Hanna Musgrave,Sophie Nambot,Catherine Nogues,Jan Oosterwijk,Dominique Stoppa-Lyonnet,Marc Tischkowitz,Vishakha Tripathi,Marijke Wevers,Emily Zhao,Flora Leeuwen,Marjanka Schmidt,Douglas Easton,Matti Rookus,Antonis Antoniou
Journal
medRxiv
Published Date
2024
Disentangling the relationships of body mass index and circulating sex hormone concentrations in mammographic density using Mendelian randomization
PurposeMammographic 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).MethodsWe applied two-sample MR approaches to assess the association between genetically predicted circulating concentrations of sex hormones [estradiol, testosterone, sex hormone-binding globulin (SHBG)], BMI, and mammographic density phenotypes (dense and non-dense area). We created instrumental variables from large European ancestry-based genome-wide association studies and applied estimates to mammographic density phenotypes in up to 14,000 women of European …
Authors
Cameron B Haas,Hongjie Chen,Tabitha Harrison,Shaoqi Fan,Manuela Gago-Dominguez,Jose E Castelao,Manjeet K Bolla,Qin Wang,Joe Dennis,Kyriaki Michailidou,Alison M Dunning,Douglas F Easton,Antonis C Antoniou,Per Hall,Kamila Czene,Irene L Andrulis,Anna Marie Mulligan,Roger L Milne,Peter A Fasching,Lothar Haeberle,Montserrat Garcia-Closas,Thomas Ahearn,Gretchen L Gierach,Christopher Haiman,Gertraud Maskarinec,Fergus J Couch,Janet E Olson,Esther M John,Geogia Chenevix-Trench,Amy Berrington de Gonzalez,Michael Jones,Jennifer Stone,Rachel Murphy,Kristan J Aronson,Karen J Wernli,Li Hsu,Celine Vachon,Rulla M Tamimi,Sara Lindström
Journal
Breast Cancer Research and Treatment
Published Date
2024/4/24
Differences in polygenic score distributions in European ancestry populations: implications for breast cancer risk prediction
The 313-variant polygenic risk score (PRS313) provides a promising tool for breast cancer risk prediction. However, evaluation of the PRS313 across different European populations which could influence risk estimation has not been performed. Here, we explored the distribution of PRS313 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. The mean PRS313 differed markedly across European countries, being highest in south-eastern Europe and lowest in north-western Europe. Using the overall European PRS313 distribution to categorise individuals leads to overestimation and underestimation of risk in some individuals from south-eastern and north-western countries, respectively. Adjustment for principal components explained most of the observed heterogeneity in mean PRS. Country-specific PRS distributions may be used to calibrate risk categories in individuals from different countries.
Authors
Kristia Yiangou,Nasim Mavaddat,Joe Dennis,Maria Zanti,Qin Wang,Manjeet K Bolla,Mustapha Abubakar,Thomas U Ahearn,Irene L Andrulis,Hoda Anton-Culver,Natalia N Antonenkova,Volker Arndt,Kristan J Aronson,Annelie Augustinsson,Adinda Baten,Sabine Behrens,Marina Bermisheva,Amy Berrington de Gonzalez,Katarzyna Bialkowska,Nicholas Boddicker,Clara Bodelon,Natalia V Bogdanova,Stig E Bojesen,Kristen D Brantley,Hiltrud Brauch,Hermann Brenner,Nicola J Camp,Federico Canzian,Jose E Castelao,Melissa H Cessna,Jenny Chang-Claude,Georgia Chenevix-Trench,Wendy K Chung,NBCS Collaborators,Sarah V Colonna,Fergus J Couch,Angela Cox,Simon S Cross,Kamila Czene,Mary B Daly,Peter Devilee,Thilo Dork,Alison M Dunning,Diana M Eccles,A Heather Eliassen,Christoph Engel,Mikael Eriksson,D Gareth Evans,Peter A Fasching,Olivia Fletcher,Henrik Flyger,Lin Fritschi,Manuela Gago-Dominguez,Aleksandra Gentry-Maharaj,Anna Gonzalez-Neira,Pascal Guenel,Eric Hahnen,Christopher A Haiman,Ute Hamann,Jaana M Hartikainen,Vikki Ho,James Hodge,Antoinette Hollestelle,Ellen Honisch,Maartje J Hooning,Reiner Hoppe,John L Hopper,Sacha Howell,Anthony Howell,ABCTB Investigators,kConFab Investigators,Simona Jakovchevska,Anna Jakubowska,Helena Jernstrom,Nichola Johnson,Rudolf Kaaks,Elza K Khusnutdinova,Cari M Kitahara,Stella Koutros,Vessela N Kristensen,James V Lacey,Diether Lambrechts,Flavio Lejbkowicz,Annika Lindblom,Michael Lush,Arto Mannermaa,Dimitrios Mavroudis,Usha Menon,Rachel A Murphy,Heli Nevanlinna,Nadia Obi,Kenneth Offit,Tjoung-Won Park-Simon,Alpa V Patel,Cheng Peng,Paolo Peterlongo,Guillermo Pita,Dijana Plaseska-Karanfilska,Katri Pylkas,Paolo Radice,Muhammad U Rashid,Gad Rennert,Eleanor Roberts,Juan Rodriguez,Atocha Romero,Efraim H Rosenberg,Emmanouil Saloustros,Dale P Sandler,Elinor J Sawyer,Rita K Schmutzler,Christopher G Scott,Xiao-Ou Shu,Melissa C Southey,Jennifer Stone,Jack A Taylor,Lauren R Teras,Irma van de Beek,Walter Willett,Robert Winqvist,Wei Zheng,Celine M Vachon,Marjanka K Schmidt,Per Hall,Robert J MacInnis,Roger L Milne,Paul DP Pharoah,Jacques Simard,Antonis C Antoniou,Douglas F Easton,Kyriaki Michailidou
Journal
medRxiv
Published Date
2024
Age-specific breast and ovarian cancer risks associated with germline BRCA1 or BRCA2 pathogenic variants–an Asian study of 572 families
BackgroundClinical management of Asian BRCA1 and BRCA2 pathogenic variants (PV) carriers remains challenging due to imprecise age-specific breast (BC) and ovarian cancer (OC) risks estimates. We aimed to refine these estimates using six multi-ethnic studies in Asia.MethodsData were collected on 271 BRCA1 and 301 BRCA2 families from Malaysia and Singapore, ascertained through population/hospital-based case-series (88%) and genetic clinics (12%). Age-specific cancer risks were estimated using a modified segregation analysis method, adjusted for ascertainment.FindingsBC and OC relative risks (RRs) varied across age groups for both BRCA1 and BRCA2. The age-specific RR estimates were similar across ethnicities and country of residence. For BRCA1 carriers of Malay, Indian and Chinese ancestry born between 1950 and 1959 in Malaysia, the cumulative risk (95% CI) of BC by age 80 was 40 …
Authors
Weang-Kee Ho,Nur Tiara Hassan,Sook-Yee Yoon,Xin Yang,Joanna MC Lim,Nur Diana Binte Ishak,Peh Joo Ho,Eldarina A Wijaya,Patsy Pei-Sze Ng,Craig Luccarini,Jamie Allen,Mei-Chee Tai,Jianbang Chiang,Zewen Zhang,Mee-Hoong See,Meow-Keong Thong,Yin-Ling Woo,Alison M Dunning,Mikael Hartman,Cheng-Har Yip,Nur Aishah Mohd Taib,Douglas F Easton,Jingmei Li,Joanne Ngeow,Antonis C Antoniou,Soo-Hwang Teo
Journal
The Lancet Regional Health–Western Pacific
Published Date
2024/3/1
Systematic Minigene-Based Splicing Analysis and Tentative Clinical Classification of 52 CHEK2 Splice-Site Variants
Background Disrupted pre-mRNA splicing is a frequent deleterious mechanism in hereditary cancer. We aimed to functionally analyze candidate spliceogenic variants of the breast cancer susceptibility gene CHEK2 by splicing reporter minigenes. Methods A total of 128 CHEK2 splice-site variants identified in the Breast Cancer After Diagnostic Gene Sequencing (BRIDGES) project (https://cordis.europa.eu/project/id/634935) were analyzed with MaxEntScan and subsetted to 52 variants predicted to impact splicing. Three CHEK2 minigenes, which span all 15 exons, were constructed and validated. The 52 selected variants were then genetically engineered into the minigenes and assayed in MCF-7 (human breast adenocarcinoma) cells. Results Of 52 variants, 46 (88.5%) impaired splicing. Some of them led to complex splicing patterns with up to 11 different …
Authors
Lara Sanoguera-Miralles,Alberto Valenzuela-Palomo,Elena Bueno-Martínez,Ada Esteban-Sánchez,Víctor Lorca,Inés Llinares-Burguet,Alicia García-Álvarez,Pedro Pérez-Segura,Mar Infante,Douglas F Easton,Peter Devilee,Maaike PG Vreeswijk,Miguel de la Hoya,Eladio A Velasco-Sampedro
Journal
Clinical Chemistry
Published Date
2024/1
Abstract IA18: Genetic susceptibility to breast cancer: Recent advances and application to personalised prevention
The past two decades have seen dramatic progress in our understanding of the inherited basis of breast cancer, driven by large international collaborative epidemiological studies. Genetic factors identified include rare coding variants in susceptibility genes, and more than 200 common polymorphisms, identified through genome-wide association studies (GWAS) and largely in non-coding regions, that confer more moderate risks. The majority of the common variants are more strongly associated with ER-positive disease, but a subset is specifically associated with ER-negative disease. Variants are strongly enriched for regulatory regions and transcription factor binding sites, and the putative target genes are strongly enriched for known breast cancer drivers: however, the underlying target genes and mechanisms remain largely obscure. The associations for common variants appear to be largely independent of …
Authors
Douglas F Easton
Published Date
2024/2/1
Novel breast cancer susceptibility loci under linkage peaks identified in African ancestry consortia
Background Expansion of genome-wide association studies across population groups is needed to improve our understanding of shared and unique genetic contributions to breast cancer. We performed association and replication studies guided by a priori linkage findings from African ancestry (AA) relative pairs. Methods We performed fixed-effect inverse-variance weighted meta-analysis under three significant AA breast cancer linkage peaks (3q26-27, 12q22-23, and 16q21-22) in 9241 AA cases and 10 193 AA controls. We examined associations with overall breast cancer as well as estrogen receptor (ER)-positive and negative subtypes (193,132 SNPs). We replicated associations in the African-ancestry Breast Cancer Genetic Consortium (AABCG). Results In AA women, we identified two associations on chr12q for overall breast cancer (rs1420647 …
Authors
Heather M Ochs-Balcom,Leah Preus,Zhaohui Du,Robert C Elston,Craig C Teerlink,Guochong Jia,Xingyi Guo,Qiuyin Cai,Jirong Long,Jie Ping,Bingshan Li,Daniel O Stram,Xiao-Ou Shu,Maureen Sanderson,Guimin Gao,Thomas Ahearn,Kathryn L Lunetta,Gary Zirpoli,Melissa A Troester,Edward A Ruiz-Narváez,Stephen A Haddad,Jonine Figueroa,Esther M John,Leslie Bernstein,Jennifer J Hu,Regina G Ziegler,Sarah Nyante,Elisa V Bandera,Sue A Ingles,Nicholas Mancuso,Michael F Press,Sandra L Deming,Jorge L Rodriguez-Gil,Song Yao,Temidayo O Ogundiran,Oladosu Ojengbede,Manjeet K Bolla,Joe Dennis,Alison M Dunning,Douglas F Easton,Kyriaki Michailidou,Paul DP Pharoah,Dale P Sandler,Jack A Taylor,Qin Wang,Katie M O’Brien,Clarice R Weinberg,Cari M Kitahara,William Blot,Katherine L Nathanson,Anselm Hennis,Barbara Nemesure,Stefan Ambs,Lara E Sucheston-Campbell,Jeannette T Bensen,Stephen J Chanock,Andrew F Olshan,Christine B Ambrosone,Olufunmilayo I Olopade,Ghana Breast Health Study Team,David V Conti,Julie Palmer,Montserrat García-Closas,Dezheng Huo,Wei Zheng,Christopher Haiman
Journal
Human molecular genetics
Published Date
2024/1/23
Estimation of age of onset and progression of breast cancer by absolute risk dependent on polygenic risk score and other risk factors
The age at which individuals with breast cancer enter a screen‐detectable state, as opposed to the length of time spent in that state, varied by absolute risk group.
Authors
Rikesh Bhatt,Ardo van den Hout,Antonis C Antoniou,Mitul Shah,Lorenzo Ficorella,Emily Steggall,Douglas F Easton,Paul DP Pharoah,Nora Pashayan
Journal
Cancer
Published Date
2024/1/4
Professor FAQs
What is Douglas Easton's h-index at University of Cambridge?
The h-index of Douglas Easton has been 114 since 2020 and 208 in total.
What are Douglas Easton's top articles?
The articles with the titles of
Validation of the BOADICEA Model in a Prospective cohort of BRCA1/2 Pathogenic Variant Carriers
Disentangling the relationships of body mass index and circulating sex hormone concentrations in mammographic density using Mendelian randomization
Differences in polygenic score distributions in European ancestry populations: implications for breast cancer risk prediction
Age-specific breast and ovarian cancer risks associated with germline BRCA1 or BRCA2 pathogenic variants–an Asian study of 572 families
Systematic Minigene-Based Splicing Analysis and Tentative Clinical Classification of 52 CHEK2 Splice-Site Variants
Abstract IA18: Genetic susceptibility to breast cancer: Recent advances and application to personalised prevention
Novel breast cancer susceptibility loci under linkage peaks identified in African ancestry consortia
Estimation of age of onset and progression of breast cancer by absolute risk dependent on polygenic risk score and other risk factors
...
are the top articles of Douglas Easton at University of Cambridge.
What are Douglas Easton's research interests?
The research interests of Douglas Easton are: Genetic Epidemiology, Cancer Epidemiology, Statistical Genetics
What is Douglas Easton's total number of citations?
Douglas Easton has 199,884 citations in total.
What are the co-authors of Douglas Easton?
The co-authors of Douglas Easton are Paul Pharoah, Per Hall, Alison M Dunning, Diana Eccles, D. Timothy Bishop.