Joe Dennis

University of Cambridge

H-index: 77

Europe-United Kingdom

About Joe Dennis

Joe Dennis, With an exceptional h-index of 77 and a recent h-index of 62 (since 2020), a distinguished researcher at University of Cambridge, specializes in the field of Cancer Genetics, Bioinformatics.

His recent articles reflect a diverse array of research interests and contributions to the field:

Novel breast cancer susceptibility loci under linkage peaks identified in African ancestry consortia

Large-scale genome-wide association study of 398,238 women unveils seven novel loci associated with high-grade serous epithelial ovarian cancer risk

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

Copy Number Variants Associated with Epithelial Ovarian Cancer Risk in the Population

Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer‐specific survival

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Exome sequencing identifies breast cancer susceptibility genes and defines the contribution of coding variants to breast cancer risk (vol 55, pg 1435, 2023)

Joe Dennis Information

University	University of Cambridge
Position	___
Citations(all)	26390
Citations(since 2020)	17717
Cited By	26668
hIndex(all)	77
hIndex(since 2020)	62
i10Index(all)	189
i10Index(since 2020)	168
Email	Access Email
University Profile Page	University of Cambridge

Joe Dennis Skills & Research Interests

Cancer Genetics

Bioinformatics

Top articles of Joe Dennis

Novel breast cancer susceptibility loci under linkage peaks identified in African ancestry consortia

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

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 …

Large-scale genome-wide association study of 398,238 women unveils seven novel loci associated with high-grade serous epithelial ovarian cancer risk

Authors

Daniel R Barnes,Jonathan P Tyrer,Joe Dennis,Goska Leslie,Manjeet K Bolla,Michael Lush,Amber M Aeilts,Kristiina Aittomaki,Nadine Andrieu,Irene L Andrulis,Hoda Anton-Culver,Adalgeir Arason,Banu K Arun,Judith Balmaña,Elisa V Bandera,Rosa B Barkardottir,Lieke PV Berger,Amy Berrington de Gonzalez,Pascaline Berthet,Katarzyna Bialkowska,Line Bjorge,Amie M Blanco,Marinus J Blok,Kristie A Bobolis,Natalia V Bogdanova,James D Brenton,Henriett Butz,Saundra S Buys,Maria A Caligo,Ian Campbell,Carmen Castillo,Kathleen BM Claes,GEMO Study Collaborators,EMBRACE Collaborators,Sarah V Colonna,Linda S Cook,Mary B Daly,Agnieszka Dansonka-Mieszkowska,Miguel de la Hoya,Anna deFazio,Allison DePersia,Yuan Chun Ding,Susan M Domchek,Thilo Dork,Zakaria Einbeigi,Christoph Engel,D Gareth Evans,Lenka Foretova,Renee T Fortner,Florentia Fostira,Maria Cristina Foti,Eitan Friedman,Megan N Frone,Patricia A Ganz,Aleksandra Gentry-Maharaj,Gord Glendon,Andrew K Godwin,Anna Gonzalez-Neira,Mark H Greene,Jacek Gronwald,Aliana Guerrieri-Gonzaga,Ute Hamann,Thomas vO Hansen,Holly R Harris,Jan Hauke,Florian Heitz,Frans BL Hogervorst,Maartje J Hooning,John L Hopper,Chad D Huff,David G Huntsman,Evgeny N Imyanitov,kConFab Investigators,Louise Izatt,Anna Jakubowska,Paul A James,Ramunas Janavicius,Esther M John,Siddhartha Kar,Beth Y Karlan,Catherine J Kennedy,Lambertus ALM Kiemeney,Irene Konstantopoulou,Jolanta Kupryjanczyk,Yael Laitman,Ofer Lavie,Kate Lawrenson,Jenny Lester,Fabienne Lesueur,Carlos Lopez Pleguezuelos,Phuong L Mai,Siranoush Manoukian,Taymaa May,Iain A McNeish,Usha Menon,Roger L Milne,Francesmary Modugno,Jennifer M Mongiovi,Marco Montagna,Kirsten B Moysich,Susan L Neuhausen,Finn C Nielsen,Catherine Nogues,Edit Olah,Olufunmilayo I Olopade,Ana Osorio,Laura Papi,Harsh Pathak,Celeste L Pearce,Inge S Pedersen,Ana Peixoto,Tanja Pejovic,Pei-Chen Peng,Beth N Peshkin,Paolo Peterlongo,C Bethan Powell,Darya Prokofyeva,Miquel Angel Pujana,Paolo Radice,Muhammad U Rashid,Gad Rennert,George Richenberg,Dale P Sandler,Naoko Sasamoto,Veronica W Setiawan,Priyanka Sharma,Weiva Sieh,Christian F Singer,Katie Snape,Anna P Sokolenko,Penny Soucy,Melissa C Southey,Dominique Stoppa-Lyonnet,Rebecca Sutphen,Christian Sutter,Manuel R Teixeira,Kathryn L Terry,Liv Cecilie V Thomsen,Marc Tischkowitz,Amanda E Toland,Toon Van Gorp,Ana Vega,Digna R Velez Edwards,Penelope M Webb,Jeffrey N Weitzel,Nicolas Wentzensen,Alice S Whittemore,Stacey J Winham,Anna H Wu,Siddhartha Yadav

Journal

medRxiv

Published Date

2024

Background Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We used data from the Ovarian Cancer Association Consortium (OCAC), Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA), UK Biobank (UKBB), and FinnGen to identify novel HGSOC susceptibility loci and develop polygenic scores (PGS). Methods We analyzed >22 million variants for 398,238 women. Associations were assessed separately by consortium and meta-analysed. OCAC and CIMBA data were used to develop PGS which were trained on FinnGen data and validated in UKBB and BioBank Japan. Results Eight novel variants were associated with HGSOC risk. An interesting discovery biologically was finding that TP53 3'-UTR SNP rs78378222 was associated with HGSOC (per T allele relative risk (RR)=1.44, 95%CI:1.28-1.62, P=1.76x10-9). The optimal PGS included 64,518 variants and was associated with an odds ratio of 1.46 (95%CI:1.37-1.54) per standard deviation in the UKBB validation (AUROC curve=0.61, 95%CI:0.59-0.62). Conclusions This study represents the largest GWAS for HGSOC to date. The results highlight that improvements in imputation reference panels and increased sample sizes can identify HGSOC associated variants that previously went undetected, resulting in improved PGS. The use of updated PGS in cancer risk prediction algorithms will then improve personalized risk prediction for HGSOC.

Disentangling the relationships of body mass index and circulating sex hormone concentrations in mammographic density using Mendelian randomization

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

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 …

Differences in polygenic score distributions in European ancestry populations: implications for breast cancer risk prediction

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

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.

Copy Number Variants Associated with Epithelial Ovarian Cancer Risk in the Population

Authors

Douglas Easton,Joe Dennis

Published Date

2023/1/27

Background Known risk alleles for epithelial ovarian cancer (EOC) account for~ 40% of the narrow-sense heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort. Methods Single nucleotide polymorphism array data from 13,071 EOC cases and 17,306 controls of White European ancestry was used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer related cell types. Results We identified significant risk associations with CNVs at known EOC risk genes; BRCA1 (P= 1.60 x10-21), RAD51C (P= 5.5 x10-4) and BRCA2 (P= 7.0 x10-4). Four suggestive associations (P< 0.001) were identified for rare CNVs. Risk-associated CNVs were enriched (P< 0.05) at known EOC risk loci. Non-coding CNVs were enriched in active promoters and insulators in EOC-related cell types. Conclusions CNVs in BRCA1 have been previously reported in smaller studies, but their observed frequency in this large population-based cohort, along with the CNVs observed at BRCA2 and RAD51C gene loci in EOC cases suggests that these CNVs are potentially pathogenic and may contribute to the spectrum of disease-causing mutations in these genes. CNVs are likely to occur in a wider set of susceptibility regions, with potential implications for clinical genetic testing and disease prevention.

Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer‐specific survival

Authors

Anna Morra,Maartje AC Schreurs,Irene L Andrulis,Hoda Anton‐Culver,Annelie Augustinsson,Matthias W Beckmann,Sabine Behrens,Stig E Bojesen,Manjeet K Bolla,Hiltrud Brauch,Annegien Broeks,Saundra S Buys,Nicola J Camp,Jose E Castelao,Melissa H Cessna,Jenny Chang‐Claude,Wendy K Chung,NBCS Collaborators,Kristine K Sahlberg,Anne‐Lise Børresen‐Dale,Inger Torhild Gram,Karina Standahl Olsen,Olav Engebråten,Bjørn Naume,Jürgen Geisler,OSBREAC,Grethe I Grenaker Alnæs,Sarah V Colonna,Fergus J Couch,Angela Cox,Simon S Cross,Kamila Czene,Mary B Daly,Joe Dennis,Peter Devilee,Thilo Dörk,Alison M Dunning,Miriam Dwek,Douglas F Easton,Diana M Eccles,Mikael Eriksson,D Gareth Evans,Peter A Fasching,Tanja N Fehm,Jonine D Figueroa,Henrik Flyger,Marike Gabrielson,Manuela Gago‐Dominguez,Montserrat García‐Closas,José A García‐Sáenz,Jeanine Genkinger,Felix Grassmann,Melanie Gündert,Eric Hahnen,Christopher A Haiman,Ute Hamann,Patricia A Harrington,Jaana M Hartikainen,Reiner Hoppe,John L Hopper,Richard S Houlston,Anthony Howell,ABCTB Investigators,Christine Clarke,Deborah Marsh,Rodney Scott,Robert Baxter,Desmond Yip,Jane Carpenter,Alison Davis,Nirmala Pathmanathan,Peter Simpson,J Dinny Graham,Mythily Sachchithananthan,kConFab Investigators,David Amor,Lesley Andrews,Yoland Antill,Rosemary Balleine,Jonathan Beesley,Ian Bennett,Michael Bogwitz,Leon Botes,Meagan Brennan,Melissa Brown,Michael Buckley,Jo Burke,Phyllis Butow,Liz Caldon,Ian Campbell,Michelle Cao,Anannya Chakrabarti,Deepa Chauhan,Manisha Chauhan,Georgia Chenevix‐Trench,Alice Christian,Paul Cohen,Alison Colley,Ashley Crook,James Cui,Eliza Courtney,Margaret Cummings,Sarah‐Jane Dawson,Anna DeFazio,Martin Delatycki,Rebecca Dickson,Joanne Dixon,Ted Edkins,Stacey Edwards,Gelareh Farshid,Andrew Fellows,Georgina Fenton,Michael Field,James Flanagan,Peter Fong,Laura Forrest,Stephen Fox,Juliet French,Michael Friedlander,Clara Gaff,Mike Gattas,Peter George,Sian Greening,Marion Harris,Stewart Hart,Nick Hayward,John Hopper,Cass Hoskins,Clare Hunt,Paul James,Mark Jenkins,Alexa Kidd,Judy Kirk,Jessica Koehler,James Kollias,Sunil Lakhani,Mitchell Lawrence,Jason Lee,Shuai Li,Geoff Lindeman,Lara Lipton,Liz Lobb,Sherene Loi,Graham Mann,Deborah Marsh,Sue Anne McLachlan,Bettina Meiser,Roger Milne,Sophie Nightingale,Shona O’Connell

Journal

Cancer medicine

Published Date

2023/8

Background Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC‐specific survival (BCSS) compared to non‐carriers. Aim To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Methods Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow‐up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi‐state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. Results There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association …

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Authors

Bang Zheng,Giulia Vivaldi,Luke Daines,Olivia C Leavy,Matthew Richardson,Omer Elneima,Hamish JC McAuley,Aarti Shikotra,Amisha Singapuri,Marco Sereno,Ruth M Saunders,Victoria C Harris,Linzy Houchen-Wolloff,Neil J Greening,Paul E Pfeffer,John R Hurst,Jeremy S Brown,Manu Shankar-Hari,Carlos Echevarria,Anthony De Soyza,Ewen M Harrison,Annemarie B Docherty,Nazir Lone,Jennifer K Quint,James D Chalmers,Ling-Pei Ho,Alex Horsley,Michael Marks,Krishna Poinasamy,Betty Raman,Liam G Heaney,Louise V Wain,Rachael A Evans,Christopher E Brightling,Adrian Martineau,Aziz Sheikh,K Abel,H Adamali,D Adeloye,O Adeyemi,R Adrego,LA Aguilar Jimenez,S Ahmad,N Ahmad Haider,R Ahmed,N Ahwireng,M Ainsworth,B Al-Sheklly,A Alamoudi,M Ali,M Aljaroof,AM All,L Allan,RJ Allen,L Allerton,L Allsop,P Almeida,D Altmann,M Alvarez Corral,S Amoils,D Anderson,C Antoniades,G Arbane,A Arias,C Armour,L Armstrong,N Armstrong,D Arnold,H Arnold,A Ashish,A Ashworth,M Ashworth,S Aslani,H Assefa-Kebede,C Atkin,P Atkin,R Aul,H Aung,L Austin,C Avram,A Ayoub,M Babores,R Baggott,J Bagshaw,D Baguley,L Bailey,JK Baillie,S Bain,M Bakali,M Bakau,E Baldry,D Baldwin,M Baldwin,C Ballard,A Banerjee,B Bang,RE Barker,L Barman,S Barratt,F Barrett,D Basire,N Basu,M Bates,A Bates,R Batterham,H Baxendale,H Bayes,M Beadsworth,P Beckett,M Beggs,M Begum,P Beirne,D Bell,R Bell,K Bennett,E Beranova,A Bermperi,A Berridge,C Berry,S Betts,E Bevan,K Bhui,M Bingham,K Birchall,L Bishop,K Bisnauthsing,J Blaikely,A Bloss,A Bolger,CE Bolton,J Bonnington,A Botkai,C Bourne,M Bourne,K Bramham,L Brear,G Breen,J Breeze,A Briggs,E Bright,CE Brightling,S Brill,K Brindle,L Broad,A Broadley,C Brookes,M Broome,A Brown,J Brown,JS Brown

Journal

The Lancet Regional Health–Europe

Published Date

2023/6/1

BackgroundThe risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea.MethodsWe used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up …

Exome sequencing identifies breast cancer susceptibility genes and defines the contribution of coding variants to breast cancer risk (vol 55, pg 1435, 2023)

Authors

Naomi Wilcox,Martine Dumont,Anna Gonzalez-Neira,Sara Carvalho,Charles Joly Beauparlant,Marco Crotti,Craig Luccarini,Penny Soucy,Stephane Dubois,Rocio Nunez-Torres,Guillermo Pita,Eugene J Gardner,Joe Dennis,M Rosario Alonso,Nuria Alvarez,Caroline Baynes,Annie Claude Collin-Deschesnes,Sylvie Desjardins,Heiko Becher,Sabine Behrens,Manjeet K Bolla,Jose E Castelao,Jenny Chang-Claude,Sten Cornelissen,Thilo Dork,Christoph Engel,Manuela Gago-Dominguez,Pascal Guenel,Andreas Hadjisavvas,Eric Hahnen,Mikael Hartman,Belen Herraez,Audrey Jung,Renske Keeman,Marion Kiechle,Jingmei Li,Maria A Loizidou,Michael Lush,Kyriaki Michailidou,Mihalis I Panayiotidis,Xueling Sim,Soo Hwang Teo,Jonathan P Tyrer,Lizet E van der Kolk,Cecilia Wahlstrom,Qin Wang,John RB Perry,Javier Benitez,Marjanka K Schmidt,Rita K Schmutzler,Paul DP Pharoah,Arnaud Droit,Alison M Dunning,Anders Kvist,Peter Devilee,Douglas F Easton,Jacques Simard

Published Date

2023/11/1

Correction to: Nature Genetics, published online 17 August 2023. In the version of the article initially published, in the sentence in the Abstract now reading “Associations were also observed for LZTR1, ATRIP and BARD1 with P < 1 × 10−4”, “ATRIP” appeared incorrectly as “ATR”. This has now been corrected in the PDF and HTML versions of the article.

Large-scale meta–genome-wide association study reveals common genetic factors linked to radiation-induced acute toxicities across cancer types

Authors

Elnaz Naderi,Miguel E Aguado-Barrera,Line MH Schack,Leila Dorling,Tim Rattay,Laura Fachal,Holly Summersgill,Laura Martínez-Calvo,Ceilidh Welsh,Tom Dudding,Yasmin Odding,Ana Varela-Pazos,Rajesh Jena,David J Thomson,Roel JHM Steenbakkers,Joe Dennis,Ramón Lobato-Busto,Jan Alsner,Andy Ness,Chris Nutting,Antonio Gómez-Caamaño,Jesper G Eriksen,Steve J Thomas,Amy M Bates,Adam J Webb,Ananya Choudhury,Barry S Rosenstein,Begona Taboada-Valladares,Carsten Herskind,David Azria,David P Dearnaley,Dirk de Ruysscher,Elena Sperk,Emma Hall,Hilary Stobart,Jenny Chang-Claude,Kim De Ruyck,Liv Veldeman,Manuel Altabas,Maria Carmen De Santis,Marie-Pierre Farcy-Jacquet,Marlon R Veldwijk,Matthew R Sydes,Matthew Parliament,Nawaid Usmani,Neil G Burnet,Petra Seibold,R Paul Symonds,Rebecca M Elliott,Renée Bultijnck,Sara Gutiérrez-Enríquez,Meritxell Mollà,Sarah L Gulliford,Sheryl Green,Tiziana Rancati,Victoria Reyes,Ana Carballo,Paula Peleteiro,Paloma Sosa-Fajardo,Chris Parker,Valérie Fonteyne,Kerstie Johnson,Maarten Lambrecht,Ben Vanneste,Riccardo Valdagni,Alexandra Giraldo,Mónica Ramos,Brenda Diergaarde,Geoffrey Liu,Suzanne M Leal,Melvin LK Chua,Miranda Pring,Jens Overgaard,Luis M Cascallar-Caneda,Fréderic Duprez,Christopher J Talbot,Gillian C Barnett,Alison M Dunning,Ana Vega,Christian Nicolaj Andreassen,Johannes A Langendijk,Catharine ML West,Behrooz Z Alizadeh,Sarah L Kerns

Journal

JNCI Cancer Spectrum

Published Date

2023/12/1

Background This study was designed to identify common genetic susceptibility and shared genetic variants associated with acute radiation-induced toxicity across 4 cancer types (prostate, head and neck, breast, and lung). Methods A genome-wide association study meta-analysis was performed using 19 cohorts totaling 12 042 patients. Acute standardized total average toxicity (STATacute) was modelled using a generalized linear regression model for additive effect of genetic variants, adjusted for demographic and clinical covariates (rSTATacute). Linkage disequilibrium score regression estimated shared single-nucleotide variation (SNV—formerly SNP)–based heritability of rSTATacute in all patients and for each cancer type. Results Shared SNV-based heritability of STATacute among all cancer types was estimated at 10% (SE = 0.02) and was …

Prevalence of physical frailty, including risk factors, up to 1 year after hospitalisation for COVID-19 in the UK: a multicentre, longitudinal cohort study

Authors

Hamish JC McAuley,Rachael A Evans,Charlotte E Bolton,Christopher E Brightling,James D Chalmers,Annemarie B Docherty,Omer Elneima,Paul L Greenhaff,Ayushman Gupta,Victoria C Harris,Ewen M Harrison,Ling-Pei Ho,Alex Horsley,Linzy Houchen-Wolloff,Caroline J Jolley,Olivia C Leavy,Nazir I Lone,William DC Man,Michael Marks,Dhruv Parekh,Krisnah Poinasamy,Jennifer K Quint,Betty Raman,Matthew Richardson,Ruth M Saunders,Marco Sereno,Aarti Shikotra,Amisha Singapuri,Sally J Singh,Michael Steiner,Ai Lyn Tan,Louise V Wain,Carly Welch,Julie Whitney,Miles D Witham,Janet Lord,Neil J Greening,K Abel,H Adamali,D Adeloye,O Adeyemi,R Adrego,LA Aguilar Jimenez,S Ahmad,N Ahmad Haider,R Ahmed,N Ahwireng,M Ainsworth,B Al-Sheklly,A Alamoudi,M Ali,M Aljaroof,AM All,L Allan,RJ Allen,L Allerton,L Allsop,P Almeida,D Altmann,M Alvarez Corral,S Amoils,D Anderson,C Antoniades,G Arbane,A Arias,C Armour,L Armstrong,N Armstrong,D Arnold,H Arnold,A Ashish,A Ashworth,M Ashworth,S Aslani,H Assefa-Kebede,C Atkin,P Atkin,R Aul,H Aung,L Austin,C Avram,A Ayoub,M Babores,R Baggott,J Bagshaw,D Baguley,L Bailey,JK Baillie,S Bain,M Bakali,M Bakau,E Baldry,D Baldwin,M Baldwin,C Ballard,A Banerjee,B Bang,RE Barker,L Barman,S Barratt,F Barrett,D Basire,N Basu,M Bates,A Bates,R Batterham,H Baxendale,H Bayes,M Beadsworth,P Beckett,M Beggs,M Begum,P Beirne,D Bell,R Bell,K Bennett,E Beranova,A Bermperi,A Berridge,C Berry,S Betts,E Bevan,K Bhui,M Bingham,K Birchall,L Bishop,K Bisnauthsing,J Blaikely,A Bloss,A Bolger,CE Bolton,J Bonnington,A Botkai,C Bourne,M Bourne,K Bramham,L Brear,G Breen,J Breeze,A Briggs,E Bright,CE Brightling,S Brill,K Brindle,L Broad,A Broadley,C Brookes,M Broome,A Brown,J Brown

Journal

EClinicalMedicine

Published Date

2023/3/1

BackgroundThe scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty.MethodsThis prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group—robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)—at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of …

Spectrum and Frequency of Germline FANCM Protein-Truncating Variants in 44,803 European Female Breast Cancer Cases

Authors

Gisella Figlioli,Amandine Billaud,Qin Wang,Manjeet K Bolla,Joe Dennis,Michael Lush,Anders Kvist,Muriel A Adank,Thomas U Ahearn,Natalia N Antonenkova,Päivi Auvinen,Sabine Behrens,Marina Bermisheva,Natalia V Bogdanova,Stig E Bojesen,Bernardo Bonanni,Thomas Brüning,Nicola J Camp,Archie Campbell,Jose E Castelao,Melissa H Cessna,NBCS Collaborators,Kamila Czene,Peter Devilee,Thilo Dörk,Mikael Eriksson,Peter A Fasching,Henrik Flyger,Marike Gabrielson,Manuela Gago-Dominguez,Montserrat García-Closas,Gord Glendon,Encarna B Gómez Garcia,Anna González-Neira,Felix Grassmann,Pascal Guénel,Eric Hahnen,Ute Hamann,Peter Hillemanns,Maartje J Hooning,Reiner Hoppe,Anthony Howell,Keith Humphreys,kConFab Investigators,Anna Jakubowska,Elza K Khusnutdinova,Vessela N Kristensen,Annika Lindblom,Maria A Loizidou,Jan Lubiński,Arto Mannermaa,Tabea Maurer,Dimitrios Mavroudis,William G Newman,Nadia Obi,Mihalis I Panayiotidis,Paolo Radice,Muhammad U Rashid,Valerie Rhenius,Matthias Ruebner,Emmanouil Saloustros,Elinor J Sawyer,Marjanka K Schmidt,Rita K Schmutzler,Mitul Shah,Melissa C Southey,Ian Tomlinson,Thérèse Truong,Elke M van Veen,Camilla Wendt,Xiaohong R Yang,Kyriaki Michailidou,Alison M Dunning,Paul DP Pharoah,Douglas F Easton,Irene L Andrulis,D Gareth Evans,Antoinette Hollestelle,Jenny Chang-Claude,Roger L Milne,Paolo Peterlongo

Journal

Cancers

Published Date

2023/6/23

Simple Summary Mutations in the FANCM gene may cause a particular type of breast cancer known as ER-negative. In this study, we describe the geographic distribution of 66 different FANCM mutations identified in 44,803 female breast cancer cases from Europe, USA, Canada and Australia. We found that the FANCM:p.Gln1701* mutation is most common in Northern Europe and has lower frequencies in Southern European countries. In contrast, the FANCM:p.Gly1906Alafs*12 mutation is most common in Southern Europe and rarer in Central and Northern Europe. We found that the FANCM:p.Arg658* mutation is most prevalent in Central Europe and that the FANCM:p.Gln498Thrfs*7 mutation originates from Lithuania. Finally, we showed that many and varied FANCM mutations are present in Southwestern and Central Europeans while a much more limited range of mutations is present in Northeastern Europeans. The knowledge of this geographic distribution of FANCM mutations is important to establish more efficient genetic testing strategies in specific populations. Abstract FANCM germline protein truncating variants (PTVs) are moderate-risk factors for ER-negative breast cancer. We previously described the spectrum of FANCM PTVs in 114 European breast cancer cases. In the present, larger cohort, we report the spectrum and frequency of four common and 62 rare FANCM PTVs found in 274 carriers detected among 44,803 breast cancer cases. We confirmed that p.Gln1701* was the most common PTV in Northern Europe with lower frequencies in Southern Europe. In contrast, p.Gly1906Alafs*12 was the …

Polymorphisms in genes of melatonin biosynthesis and signaling support the light-at-night hypothesis for breast cancer

Authors

Katharina Wichert,Reiner Hoppe,Katja Ickstadt,Thomas Behrens,Stefan Winter,Robert Herold,Claudia Terschüren,Wing-Yee Lo,Pascal Guénel,Thérèse Truong,Manjeet K Bolla,Qin Wang,Joe Dennis,Kyriaki Michailidou,Michael Lush,Irene L Andrulis,Hermann Brenner,Jenny Chang-Claude,Angela Cox,Simon S Cross,Kamila Czene,Mikael Eriksson,Jonine D Figueroa,Montserrat García-Closas,Mark S Goldberg,Ute Hamann,Wei He,Bernd Holleczek,John L Hopper,Anna Jakubowska,Yon-Dschun Ko,Jan Lubiński,Anna Marie Mulligan,Nadia Obi,Valerie Rhenius,Mitul Shah,Xiao-Ou Shu,Jacques Simard,Melissa C Southey,Wei Zheng,Alison M Dunning,Paul DP Pharoah,Per Hall,Douglas F Easton,Thomas Brüning,Hiltrud Brauch,Volker Harth,Sylvia Rabstein

Journal

European journal of epidemiology

Published Date

2023/10

Light-at-night triggers the decline of pineal gland melatonin biosynthesis and secretion and is an IARC-classified probable breast-cancer risk factor. We applied a large-scale molecular epidemiology approach to shed light on the putative role of melatonin in breast cancer. We investigated associations between breast-cancer risk and polymorphisms at genes of melatonin biosynthesis/signaling using a study population of 44,405 women from the Breast Cancer Association Consortium (22,992 cases, 21,413 population-based controls). Genotype data of 97 candidate single nucleotide polymorphisms (SNPs) at 18 defined gene regions were investigated for breast-cancer risk effects. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CI) by logistic regression for the main-effect analysis as well as stratified analyses by estrogen- and progesterone-receptor (ER, PR) status. SNP-SNP interactions …

Long COVID research: an update from the PHOSP-COVID Scientific Summit

Authors

Christopher E Brightling,Rachael A Evans,Amisha Singapuri,Nikki Smith,Louise V Wain,CE Brightling,RA Evans,LV Wain,JD Chalmers,VC Harris,LP Ho,A Horsley,L Houchen-Wolloff,M Marks,B Raman,A Singapuri,P Barran,M Bingham,ER Chilvers,E Daynes,CM Efstathiou,O Elneima,B Guillen Guio,EM Harrison,RG Jenkins,F Liew,NI Lone,JM Lord,HJC McAuley,GP McCann,J Mitchell,T Plekhanova,RJ Russell,RM Saunders,MG Semple,N Smith,D Trivedi,L Turtle,S Walker,K Abel,H Adamali,D Adeloye,O Adeyemi,R Adrego,LA Aguilar Jimenez,S Ahmad,N Ahmad Haider,R Ahmed,N Ahwireng,M Ainsworth,B Al-Sheklly,A Alamoudi,M Ali,M Aljaroof,L Allan,RJ Allen,L Allerton,L Allsop,AM Allt,P Almeida,D Altmann,M Alvarez Corral,S Amoils,D Anderson,C Antoniades,G Arbane,A Arias,C Armour,L Armstrong,N Armstrong,D Arnold,H Arnold,A Ashish,A Ashworth,M Ashworth,S Aslani,H Assefa-Kebede,P Atkin,C Atkin,R Aul,H Aung,L Austin,C Avram,A Ayoub,M Babores,R Baggott,J Bagshaw,D Baguley,L Bailey,JK Baillie,S Bain,M Bakali,M Bakau,E Baldry,M Baldwin,D Baldwin,C Ballard,A Banerjee,D Bang,RE Barker,L Barman,S Barratt,F Barrett,D Basire,N Basu,M Bates,A Bates,R Batterham,H Baxendale,G Baxter,H Bayes,M Beadsworth,P Beckett,M Beggs,M Begum,P Beirne,M Bell,R Bell,K Bennett,E Beranova,A Bermperi,A Berridge,C Berry,S Betts,E Bevan,K Bhui,K Birchall,L Bishop,K Bisnauthsing,J Blaikely,A Bloss,A Bolger,CE Bolton,J Bonnington,A Botkai,C Bourne,M Bourne,K Bramham,L Brear,G Breen,J Breeze,K Breeze,A Briggs,E Bright,S Brill,K Brindle,L Broad,A Broadley,C Brookes,M Broome

Journal

The Lancet Respiratory Medicine

Published Date

2023/11/1

The severity of acute SARS-CoV-2 infection has decreased with the introduction of public health policies, vaccination, improved management of acute disease, and a degree of protective immunity in those who have survived past infection. However, in the wake of the pandemic, post-acute sequelae of COVID-19—referred to as long COVID—have emerged. The UK National Institute for Health and Care Excellence (NICE) describes long COVID as a condition in which signs and symptoms continue or develop after acute COVID-19 (> 4 weeks), including ongoing symptomatic COVID-19 and post-COVID-19 syndrome (≥ 12 weeks). 3 years since the first UK national lockdown, the Post-hospitalisation COVID-19 study (PHOSP-COVID) held a Scientific Summit in Leicester, UK (28–29 March, 2023) to review progress and address key questions related to future research. PHOSP-COVID is a UK consortium of …

Incorporating alternative polygenic risk scores into the BOADICEA breast cancer risk prediction model

Authors

Nasim Mavaddat,Lorenzo Ficorella,Tim Carver,Andrew Lee,Alex P Cunningham,Michael Lush,Joe Dennis,Marc Tischkowitz,Kate Downes,Donglei Hu,Eric Hahnen,Rita K Schmutzler,Tracy L Stockley,Gregory S Downs,Tong Zhang,Anna M Chiarelli,Stig E Bojesen,Cong Liu,Wendy K Chung,Monica Pardo,Lidia Feliubadaló,Judith Balmaña,Jacques Simard,Antonis C Antoniou,Douglas F Easton

Journal

Cancer Epidemiology, Biomarkers & Prevention

Published Date

2023/3/6

Background The multifactorial risk prediction model BOADICEA enables identification of women at higher or lower risk of developing breast cancer. BOADICEA models genetic susceptibility in terms of the effects of rare variants in breast cancer susceptibility genes and a polygenic component, decomposed into an unmeasured and a measured component - the polygenic risk score (PRS). The current version was developed using a 313 SNP PRS. Here, we evaluated approaches to incorporating this PRS and alternative PRS in BOADICEA. Methods The mean, SD, and proportion of the overall polygenic component explained by the PRS (α2) need to be estimated. was estimated using logistic regression, where the age-specific log-OR is constrained to be a function of the age-dependent polygenic relative risk in BOADICEA; and using a retrospective likelihood (RL) approach that …

CanRisk-prostate: a comprehensive, externally validated risk model for the prediction of future prostate cancer

Authors

Tommy Nyberg,Mark N Brook,Lorenzo Ficorella,Andrew Lee,Joe Dennis,Xin Yang,Naomi Wilcox,Tokhir Dadaev,Koveela Govindasami,Michael Lush,Goska Leslie,Artitaya Lophatananon,Kenneth Muir,Elizabeth Bancroft,Douglas F Easton,Marc Tischkowitz,Zsofia Kote-Jarai,Rosalind Eeles,Antonis C Antoniou

Journal

Journal of Clinical Oncology

Published Date

2023/2/2

PURPOSEProstate cancer (PCa) is highly heritable. No validated PCa risk model currently exists. We therefore sought to develop a genetic risk model that can provide personalized predicted PCa risks on the basis of known moderate-to high-risk pathogenic variants, low-risk common genetic variants, and explicit cancer family history, and to externally validate the model in an independent prospective cohort.MATERIALS AND METHODSWe developed a risk model using a kin-cohort comprising individuals from 16,633 PCa families ascertained in the United Kingdom from 1993 to 2017 from the UK Genetic Prostate Cancer Study, and complex segregation analysis adjusting for ascertainment. The model was externally validated in 170,850 unaffected men (7,624 incident PCas) recruited from 2006 to 2010 to the independent UK Biobank prospective cohort study.RESULTSThe most parsimonious model included the …

Multi-gene panel testing and association analysis in Cypriot breast cancer cases and controls

Authors

Maria Zanti,Maria A Loizidou,Denise G O’Mahony,Leila Dorling,Joe Dennis,Peter Devilee,Douglas F Easton,Mihalis I Panayiotidis,Andreas Hadjisavvas,Kyriaki Michailidou

Journal

Frontiers in Genetics

Published Date

2023/9/18

Introduction: It is estimated that around 5% of breast cancer cases carry pathogenic variants in established breast cancer susceptibility genes. However, the underlying prevalence and gene-specific population risk estimates in Cyprus are currently unknown. Methods: We performed sequencing on a population-based case-control study of 990 breast cancer cases and 1094 controls from Cyprus using the BRIDGES sequencing panel. Analyses were conducted separately for protein-truncating and rare missense variants. Results: Protein-truncating variants in established breast cancer susceptibility genes were detected in 3.54% of cases and 0.37% of controls. Protein-truncating variants in BRCA2 and ATM were associated with a high risk of breast cancer, whereas PTVs in BRCA1 and PALB2 were associated with a high risk of estrogen receptor (ER)-negative disease. Among participants with a family history of breast cancer, PTVs in ATM, BRCA2, BRCA1, PALB2 and RAD50 were associated with an increased risk of breast cancer. Furthermore, an additional 19.70% of cases and 17.18% of controls had at least one rare missense variant in established breast cancer susceptibility genes. For BRCA1 and PALB2, rare missense variants were associated with an increased risk of overall and triple-negative breast cancer, respectively. Rare missense variants in BRCA1, ATM, CHEK2 and PALB2 domains, were associated with increased risk of disease subtypes. Conclusion: This study provides population-based prevalence and gene-specific risk estimates for protein-truncating and rare missense variants. These results may have important clinical …

Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry

Authors

Stefanie H Mueller,Alvina G Lai,Maria Valkovskaya,Kyriaki Michailidou,Manjeet K Bolla,Qin Wang,Joe Dennis,Michael Lush,Zomoruda Abu-Ful,Thomas U Ahearn,Irene L Andrulis,Hoda Anton-Culver,Natalia N Antonenkova,Volker Arndt,Kristan J Aronson,Annelie Augustinsson,Thais Baert,Laura E Beane Freeman,Matthias W Beckmann,Sabine Behrens,Javier Benitez,Marina Bermisheva,Carl Blomqvist,Natalia V Bogdanova,Stig E Bojesen,Bernardo Bonanni,Hermann Brenner,Sara Y Brucker,Saundra S Buys,Jose E Castelao,Tsun L Chan,Jenny Chang-Claude,Stephen J Chanock,Ji-Yeob Choi,Wendy K Chung,Grethe I Grenaker Alnaes,Deborah Marsh,Rodney Scott,Robert Baxter,Desmond Yip,Jane Carpenter,Alison Davis,Nirmala Pathmanathan,Peter Simpson,Dinny Graham,Mythily Sachchithananthan

Journal

Genome medicine

Published Date

2023/1/26

BackgroundLow-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.MethodsWe evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes’ coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.ResultsIn European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 × 10−6) and AC058822.1 …

Author Correction: Exome sequencing identifies breast cancer susceptibility genes and defines the contribution of coding variants to breast cancer risk

Authors

Naomi Wilcox,Martine Dumont,Anna González-Neira,Sara Carvalho,Charles Joly Beauparlant,Marco Crotti,Craig Luccarini,Penny Soucy,Stéphane Dubois,Rocio Nuñez-Torres,Guillermo Pita,Eugene J Gardner,Joe Dennis,M Rosario Alonso,Nuria Álvarez,Caroline Baynes,Annie Claude Collin-Deschesnes,Sylvie Desjardins,Heiko Becher,Sabine Behrens,Manjeet K Bolla,Jose E Castelao,Jenny Chang-Claude,Sten Cornelissen,Thilo Dörk,Christoph Engel,Manuela Gago-Dominguez,Pascal Guénel,Andreas Hadjisavvas,Eric Hahnen,Mikael Hartman,Belén Herráez,SGBCC Investigators Tan Benita Kiat-Tee 37 38 39 Tan Veronique Kiak Mien 37 38 Tan Su-Ming 40 Lim Geok Hoon 41 Tan Ern Yu 42 43 44 Ho Peh Joo 23 Khng Alexis Jiaying 23,Audrey Jung,Renske Keeman,Marion Kiechle,Jingmei Li,Maria A Loizidou,Michael Lush,Kyriaki Michailidou,Mihalis I Panayiotidis,Xueling Sim,Soo Hwang Teo,Jonathan P Tyrer,Lizet E van der Kolk,Cecilia Wahlström,Qin Wang,John RB Perry,Javier Benitez,Marjanka K Schmidt,Rita K Schmutzler,Paul DP Pharoah,Arnaud Droit,Alison M Dunning,Anders Kvist,Peter Devilee,Douglas F Easton,Jacques Simard

Journal

nature genetics

Published Date

2023/11

In the version of the article initially published, in the sentence in the Abstract now reading “Associations were also observed for LZTR1, ATRIPand BARD1with P< 1× 10− 4”,“ATRIP” appeared incorrectly as “ATR”. This has now been corrected in the PDF and HTML versions of the article.

PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants

Authors

Taru A Muranen,Anna Morra,Sofia Khan,Daniel R Barnes,Manjeet K Bolla,Joe Dennis,Renske Keeman,Goska Leslie,Michael T Parsons,Qin Wang,Thomas U Ahearn,Kristiina Aittomäki,Irene L Andrulis,Banu K Arun,Sabine Behrens,Katarzyna Bialkowska,Stig E Bojesen,Nicola J Camp,Jenny Chang-Claude,Kamila Czene,Peter Devilee,HEBON investigators,Susan M Domchek,Alison M Dunning,Christoph Engel,D Gareth Evans,Manuela Gago-Dominguez,Montserrat García-Closas,Anne-Marie Gerdes,Gord Glendon,Pascal Guénel,Eric Hahnen,Ute Hamann,Helen Hanson,Maartje J Hooning,Reiner Hoppe,Louise Izatt,Anna Jakubowska,Paul A James,Vessela N Kristensen,Fiona Lalloo,Geoffrey J Lindeman,Arto Mannermaa,Sara Margolin,Susan L Neuhausen,William G Newman,Paolo Peterlongo,Kelly-Anne Phillips,Miquel Angel Pujana,Johanna Rantala,Karina Rønlund,Emmanouil Saloustros,Rita K Schmutzler,Andreas Schneeweiss,Christian F Singer,Maija Suvanto,Yen Yen Tan,Manuel R Teixeira,Mads Thomassen,Marc Tischkowitz,Vishakha Tripathi,Barbara Wappenschmidt,Emily Zhao,Douglas F Easton,Antonis C Antoniou,Georgia Chenevix-Trench,Paul DP Pharoah,Marjanka K Schmidt,Carl Blomqvist,Heli Nevanlinna

Journal

NPJ Breast Cancer

Published Date

2023/5/12

We assessed the PREDICT v 2.2 for prognosis of breast cancer patients with pathogenic germline BRCA1 and BRCA2 variants, using follow-up data from 5453 BRCA1/2 carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC). PREDICT for estrogen receptor (ER)-negative breast cancer had modest discrimination for BRCA1 carrier patients overall (Gönen & Heller unbiased concordance 0.65 in CIMBA, 0.64 in BCAC), but it distinguished clearly the high-mortality group from lower risk categories. In an analysis of low to high risk categories by PREDICT score percentiles, the observed mortality was consistently lower than the expected mortality, but the confidence intervals always included the calibration slope. Altogether, our results encourage the use of the PREDICT ER-negative model in management of breast cancer patients with …

Large-Scale Meta-GWAS Reveals Common Genetic Factors Linked to Radiation-Induced Acute Toxicities across Cancers

Authors

Journal

JNCI cancer spectrum

Published Date

2023/12

BACKGROUND: This study was designed to identify common genetic susceptibility and shared genetic variants associated with acute radiation-induced toxicity (RIT) across four cancer types (prostate, head and neck, breast, and lung).METHODS: A GWAS meta-analysis was performed using 19 cohorts including 12,042 patients. Acute standardized total average toxicity (rSTATacute) was modelled using a generalized linear regression model for additive effect of genetic variants adjusted for demographic and clinical covariates. LD score regression estimated shared SNP-based heritability of rSTATacute in all patients and for each cancer type.RESULTS: Shared SNP-based heritability of STATacute among all cancer types was estimated at 10%(se= 0.02), and was higher for prostate (17%, se= 0.07), head and neck (27%, se= 0.09), and breast (16%, se= 0.09) cancers. We identified 130 suggestive associated SNPs with rSTATacute (5.0 x10-8< P-value< 1.0 x10-5) across 25 genomic regions. rs142667902 showed the strongest association (effect allele A; effect size-0.17; P-value= 1.7 x10-7), which is located near DPPA4, encoding a protein involved in pluripotency in stem cells, which are essential for repair of radiation-induced tissue injury. Gene-set enrichment analysis identified'RNA splicing via endonucleolytic cleavage and ligation'(P= 5.1 x10-6, Pcorrected= 0.079) as the top gene set associated with rSTATacute among all patients. In-silico gene expression analysis showed the genes associated with rSTATacute were statistically significantly up-regulated in skin (not sun exposed Pcorrected= 0.004; sun exposed Pcorrected= 0.026 …

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