Paul Pharoah

University of Cambridge

H-index: 160

Europe-United Kingdom

About Paul Pharoah

Paul Pharoah, With an exceptional h-index of 160 and a recent h-index of 99 (since 2020), a distinguished researcher at University of Cambridge, specializes in the field of Cancer, genetics, public health.

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

Exome sequencing identifies HELB as a novel susceptibility gene for non-mucinous, non-high-grade-serous epithelial ovarian cancer

Allometric versus traditional body-shape indices and risk of colorectal cancer: a Mendelian randomization analysis

Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes

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

Expression of transglutaminase-2 (TGM2) in the prognosis of female invasive breast cancer

Abstract A004: Patterns of lncRNA-regulated gene expression in high-grade serous ovarian carcinomas

Risks of second primary cancers among 584,965 female and male breast cancer survivors in England: a 25-year retrospective cohort study

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

Paul Pharoah Information

University	University of Cambridge
Position	___
Citations(all)	109209
Citations(since 2020)	46821
Cited By	82602
hIndex(all)	160
hIndex(since 2020)	99
i10Index(all)	729
i10Index(since 2020)	581
Email	Access Email
University Profile Page	University of Cambridge

Paul Pharoah Skills & Research Interests

Cancer

genetics

public health

Authors

Hend Hassan,Isaac Allen,Eleni Sofianopoulou,Yvonne Walburga,Clare Turnbull,Diana M Eccles,Marc Tischkowitz,Paul Pharoah,Antonis C Antoniou

Published Date

2023/6/25

Structured abstractObjectiveTo provide an up-to-date systematic review on “the long-term outcomes of bilateral salpingo-oophorectomy (BSO) at the time of hysterectomy” and perform a meta-analysis for the reported associations.Data sourcesWe updated a previous systematic review by searching the literature using PubMed, Web of science and Embase for publications between January 2015 and August 2022.Study eligibility criteriaWe included studies of women who had hysterectomy with BSO compared to hysterectomy with ovarian conservation or no surgery.Study appraisal and Synthesis methodsQuality of the evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). Adjusted hazard ratios were extracted and combined to obtain fixed effect estimates.ResultsHysterectomy with BSO in young women compared to hysterectomy or no surgery was …

p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study

Authors

Martin Köbel,Eun‐Young Kang,Ashley Weir,Peter F Rambau,Cheng‐Han Lee,Gregg S Nelson,Prafull Ghatage,Nicola S Meagher,Marjorie J Riggan,Jennifer Alsop,Michael S Anglesio,Matthias W Beckmann,Christiani Bisinotto,Michelle Boisen,Jessica Boros,Alison H Brand,Angela Brooks‐Wilson,Michael E Carney,Penny Coulson,Madeleine Courtney‐Brooks,Kara L Cushing‐Haugen,Cezary Cybulski,Suha Deen,Mona A El‐Bahrawy,Esther Elishaev,Ramona Erber,Sian Fereday,AOCS Group,Anna Fischer,Simon A Gayther,Arantzazu Barquin‐Garcia,Aleksandra Gentry‐Maharaj,C Blake Gilks,Helena Gronwald,Marcel Grube,Paul R Harnett,Holly R Harris,Andreas D Hartkopf,Arndt Hartmann,Alexander Hein,Joy Hendley,Brenda Y Hernandez,Yajue Huang,Anna Jakubowska,Mercedes Jimenez‐Linan,Michael E Jones,Catherine J Kennedy,Tomasz Kluz,Jennifer M Koziak,Jaime Lesnock,Jenny Lester,Jan Lubiński,Teri A Longacre,Maria Lycke,Constantina Mateoiu,Bryan M McCauley,Valerie McGuire,Britta Ney,Alexander Olawaiye,Sandra Orsulic,Ana Osorio,Luis Paz‐Ares,Teresa Ramón y Cajal,Joseph H Rothstein,Matthias Ruebner,Minouk J Schoemaker,Mitul Shah,Raghwa Sharma,Mark E Sherman,Yurii B Shvetsov,Naveena Singh,Helen Steed,Sarah J Storr,Aline Talhouk,Nadia Traficante,Chen Wang,Alice S Whittemore,Martin Widschwendter,Lynne R Wilkens,Stacey J Winham,Javier Benitez,Andrew Berchuck,David D Bowtell,Francisco J Candido dos Reis,Ian Campbell,Linda S Cook,Anna DeFazio,Jennifer A Doherty,Peter A Fasching,Renée T Fortner,María J García,Marc T Goodman,Ellen L Goode,Jacek Gronwald,David G Huntsman,Beth Y Karlan,Linda E Kelemen,Stefan Kommoss,Nhu D Le,Stewart G Martin,Usha Menon,Francesmary Modugno,Paul DP Pharoah,Joellen M Schildkraut,Weiva Sieh,Annette Staebler,Karin Sundfeldt,Anthony J Swerdlow,Susan J Ramus,James D Brenton

Journal

The Journal of Pathology: Clinical Research

Published Date

2023/5

Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high‐grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi‐institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC …

Elucidating the risk of colorectal cancer for variants in hereditary colorectal cancer genes

Authors

Khalid Mahmood,Minta Thomas,Conghui Qu,Xiaoliang Wang,Jeroen R Huyghe,Jihoon E Joo,Peter Georgeson,Volker Arndt,Sonja I Berndt,Stéphane Bézieau,Stephanie A Bien,D Timothy Bishop,Hermann Brenner,Stefanie Brezina,Andrea Burnett-Hartman,Peter T Campbell,Graham Casey,Sergi Castellví-Bel,Andrew T Chan,Jenny Chang-Claude,Xuechen Chen,David V Conti,Chiara Cremolini,Brenda Diergaarde,Jane C Figueiredo,Liesel M FitzGerald,Manuela Gago-Dominguez,Steven Gallinger,Graham G Giles,Andrea Gsu,Marc J Gunter,Jochen Hampe,Heather Hampel,Tabitha A Harrison,Michael Hoffmeister,Temitope O Keku,Anshul Kundaje,Loic Le Marchand,Heinz-Josef Lenz,Christopher I Li,Li Li,Yi Lin,Annika Lindblom,Victor Moreno,Neil Murphy,Polly A Newcomb,Christina C Newton,Mireia Obón-Santacana,Shuji Ogino,Rish K Pai,Julie R Palmer,Rachel Pearlman,Paul DP Pharoah,Amanda I Phipps,Elizabeth A Platz,John D Potter,Gad Rennert,Lori C Sakoda,Clemens Schafmayer,Stephanie L Schmit,Robert E Schoen,Martha L Slattery,Zsofia K Stadler,Robert S Steinfelder,Stephen N Thibodeau,Cornelia M Ulrich,Caroline Y Um,Franzel JB van Duijnhoven,Bethany Van Guelpen,Kala Visvanathan,Pavel Vodicka,Ludmila Vodickova,Veronika Vymetalkova,Stephanie J Weinstein,Emily White,Ingrid M Winship,Alicja Wolk,Stephen B Gruber,Mark A Jenkins,Li Hsu,Daniel D Buchanan,Ulrike Peters

Journal

Gastroenterology

Published Date

2023/10/1

The Colon Cancer Family Registry (CCFR, www. coloncfr. org) is supported in part by funding from the National Cancer Institute (NCI), National Institutes of Health (NIH)(award U01 CA167551). Support for case ascertainment was provided in part from the Surveillance, Epidemiology, and End Results (SEER) Program and the following US state cancer registries: AZ, CO, MN, NC, NH; and by the Victoria Cancer Registry (Australia) and Ontario Cancer Registry (Canada). The CCFR Set-1 (Illumina 1M/1M-Duo) and Set-2 (Illumina Omni1-Quad) scans were supported by NIH awards U01 CA122839 and R01 CA143237 (to GC). The CCFR Set-3 (Affymetrix Axiom CORECT Set array) was supported by NIH award U19 CA148107 and R01 CA81488 (to SBG). The CCFR Set-4 (Illumina OncoArray 600K SNP array) was supported by NIH award U19 CA148107 (to SBG) and by the Center for Inherited Disease Research …

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.

Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

Authors

Ceres Fernandez-Rozadilla,Maria Timofeeva,Zhishan Chen,Philip Law,Minta Thomas,Stephanie Schmit,Virginia Díez-Obrero,Li Hsu,Juan Fernandez-Tajes,Claire Palles,Kitty Sherwood,Sarah Briggs,Victoria Svinti,Kevin Donnelly,Susan Farrington,James Blackmur,Peter Vaughan-Shaw,Xiao-ou Shu,Jirong Long,Qiuyin Cai,Xingyi Guo,Yingchang Lu,Peter Broderick,James Studd,Jeroen Huyghe,Tabitha Harrison,David Conti,Christopher Dampier,Mathew Devall,Fredrick Schumacher,Marilena Melas,Gad Rennert,Mireia Obón-Santacana,Vicente Martín-Sánchez,Ferran Moratalla-Navarro,Jae Hwan Oh,Jeongseon Kim,Sun Ha Jee,Keum Ji Jung,Sun-Seog Kweon,Min-Ho Shin,Aesun Shin,Yoon-Ok Ahn,Dong-Hyun Kim,Isao Oze,Wanqing Wen,Keitaro Matsuo,Koichi Matsuda,Chizu Tanikawa,Zefang Ren,Yu-Tang Gao,Wei-Hua Jia,John Hopper,Mark Jenkins,Aung Ko Win,Rish Pai,Jane Figueiredo,Robert Haile,Steven Gallinger,Michael Woods,Polly Newcomb,David Duggan,Jeremy Cheadle,Richard Kaplan,Timothy Maughan,Rachel Kerr,David Kerr,Iva Kirac,Jan Böhm,Lukka-Pekka Mecklin,Pekka Jousilahti,Paul Knekt,Lauri Aaltonen,Harri Rissanen,Eero Pukkala,Johan Eriksson,Tatiana Cajuso,Ulrika Hänninen,Johanna Kondelin,Kimmo Palin,Tomas Tanskanen,Laura Renkonen-Sinisalo,Brent Zanke,Satu Männistö,Demetrius Albanes,Stephanie Weinstein,Edward Ruiz-Narvaez,Julie Palmer,Daniel Buchanan,Elizabeth Platz,Kala Visvanathan,Cornelia Ulrich,Erin Siegel,Stefanie Brezina,Andrea Gsur,Peter Campbell,Jenny Chang-Claude,Michael Hoffmeister,Hermann Brenner,Martha Slattery,John Potter,Konstantinos Tsilidis,Matthias Schulze,Marc Gunter,Neil Murphy,Antoni Castells,Sergi Castellví-Bel,Leticia Moreira,Volker Arndt,Anna Shcherbina,Mariana Stern,Bens Pardamean,Timothy Bishop,Graham Giles,Melissa Southey,Gregory Idos,Kevin McDonnell,Zomoroda Abu-Ful,Joel Greenson,Katerina Shulman,Flavio Lejbkowicz,Kenneth Offit,Yu-Ru Su,Robert Steinfelder,Temitope Keku,Bethany Van Guelpen,Thomas Hudson,Heather Hampel,Rachel Pearlman,Sonja Berndt,Richard Hayes,Marie Elena Martinez,Sushma Thomas,Douglas Corley,Paul Pharoah,Susanna Larsson,Yun Yen,Heinz-Josef Lenz,Emily White,Li Li,Kimberly Doheny,Elizabeth Pugh,Tameka Shelford,Andrew Chan,Marcia Cruz-Correa,Annika Lindblom,David Hunter,Amit Joshi,Clemens Schafmayer,Peter Scacheri

Journal

Nature genetics

Published Date

2023/1

Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector …

Genetically proxied glucose-lowering drug target perturbation and risk of cancer: a Mendelian randomisation analysis

Authors

James Yarmolinsky,Emmanouil Bouras,Andrei Constantinescu,Kimberley Burrows,Caroline J Bull,Emma E Vincent,Richard M Martin,Olympia Dimopoulou,Sarah J Lewis,Victor Moreno,Marijana Vujkovic,Kyong-Mi Chang,Benjamin F Voight,Philip S Tsao,Marc J Gunter,Jochen Hampe,Andrew J Pellatt,Paul DP Pharoah,Robert E Schoen,Steven Gallinger,Mark A Jenkins,Rish K Pai,Henrik Grönberg,Nora Pashayan,Johanna Schleutker,Demetrius Albanes,Stephanie Weinstein,Alicja Wolk,Catharine ML West,Lorelei A Mucci,Géraldine Cancel-Tassin,Stella Koutros,Karina Dalsgaard Sørensen,Eli Marie Grindedal,David E Neal,Freddie C Hamdy,Jenny L Donovan,Ruth C Travis,Robert J Hamilton,Sue Ann Ingles,Barry S Rosenstein,Yong-Jie Lu,Graham G Giles,Adam S Kibel,Ana Vega,Manolis Kogevinas,Kathryn L Penney,Jong Y Park,Janet L Stanford,Cezary Cybulski,Børge G Nordestgaard,Sune F Nielsen,Hermann Brenner,Christiane Maier,Jeri Kim,Esther M John,Manuel R Teixeira,Susan L Neuhausen,Kim De Ruyck,Azad Razack,Lisa F Newcomb,Davor Lessel,Radka Kaneva,Nawaid Usmani,Frank Claessens,Paul A Townsend,Jose Esteban Castelao,Monique J Roobol,Florence Menegaux,Kay-Tee Khaw,Lisa Cannon-Albright,Hardev Pandha,Stephen N Thibodeau,David J Hunter,Peter Kraft,William J Blot,Elio Riboli

Journal

Diabetologia

Published Date

2023/8

Aims/hypothesisEpidemiological studies have generated conflicting findings on the relationship between glucose-lowering medication use and cancer risk. Naturally occurring variation in genes encoding glucose-lowering drug targets can be used to investigate the effect of their pharmacological perturbation on cancer risk.MethodsWe developed genetic instruments for three glucose-lowering drug targets (peroxisome proliferator activated receptor γ [PPARG]; sulfonylurea receptor 1 [ATP binding cassette subfamily C member 8 (ABCC8)]; glucagon-like peptide 1 receptor [GLP1R]) using summary genetic association data from a genome-wide association study of type 2 diabetes in 148,726 cases and 965,732 controls in the Million Veteran Program. Genetic instruments were constructed using cis-acting genome-wide significant (p<5×10−8) SNPs permitted to be in weak linkage disequilibrium (r2<0.20). Summary …

Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel

Authors

Hagai Levi,Shai Carmi,Saharon Rosset,Rinat Yerushalmi,Aviad Zick,Tamar Yablonski-Peretz,Qin Wang,Manjeet K Bolla,Joe Dennis,Kyriaki Michailidou,Michael Lush,Thomas Ahearn,Irene L Andrulis,Hoda Anton-Culver,Antonis C Antoniou,Volker Arndt,Annelie Augustinsson,Päivi Auvinen,Laura Beane Freeman,Matthias Beckmann,Sabine Behrens,Marina Bermisheva,Clara Bodelon,Natalia V Bogdanova,Stig E Bojesen,Hermann Brenner,Helen Byers,Nicola Camp,Jose Castelao,Jenny Chang-Claude,María-Dolores Chirlaque,Wendy Chung,Christine Clarke,Margriet J Collee,Sarah Colonna,Fergus Couch,Angela Cox,Simon S Cross,Kamila Czene,Mary Daly,Peter Devilee,Thilo Dork,Laure Dossus,Diana M Eccles,A Heather Eliassen,Mikael Eriksson,Gareth Evans,Peter Fasching,Olivia Fletcher,Henrik Flyger,Lin Fritschi,Marike Gabrielson,Manuela Gago-Dominguez,Montserrat García-Closas,Jose Angel Garcia-Saenz,Jeanine Genkinger,Graham G Giles,Mark Goldberg,Pascal Guénel,Per Hall,Ute Hamann,Wei He,Peter Hillemanns,Antoinette Hollestelle,Reiner Hoppe,John Hopper,Simona Jakovchevska,Anna Jakubowska,Helena Jernström,Esther John,Nichola Johnson,Michael Jones,Joseph Vijai,Rudolf Kaaks,Elza Khusnutdinova,Cari Kitahara,Stella Koutros,Vessela Kristensen,Allison W Kurian,James Lacey,Diether Lambrechts,Loic Le Marchand,Flavio Lejbkowicz,Annika Lindblom,Sibylle Loibl,Adriana Lori,Jan Lubinski,Arto Mannermaa,Mehdi Manoochehri,Dimitrios Mavroudis,Usha Menon,AnnaMarie Mulligan,Rachel Murphy,Ines Nevelsteen,William G Newman,Nadia Obi,Katie O'Brien,Ken Offit,Andrew Olshan,Dijana Plaseska-Karanfilska,Janet Olson,Salvatore Panico,Tjoung-Won Park-Simon,Alpa Patel,Paolo Peterlongo,Brigitte Rack,Paolo Radice,Gad Rennert,Valerie Rhenius,Atocha Romero,Emmanouil Saloustros,Dale Sandler,Marjanka K Schmidt,Lukas Schwentner,Mitul Shah,Priyanka Sharma,Jacques Simard,Melissa Southey,Jennifer Stone,William J Tapper,Jack Taylor,Lauren Teras,Amanda E Toland,Melissa Troester,Thérèse Truong,Lizet E van der Kolk,Clarice Weinberg,Camilla Wendt,Xiaohong Rose Yang,Wei Zheng,Argyrios Ziogas,Alison M Dunning,Paul Pharoah,Douglas F Easton,Shay Ben-Sachar,Naama Elefant,Ron Shamir,Ran Elkon,BCAC Consortium,NBCS Collaborators,CTS Consortium,ABCTB Investigators

Journal

Journal of medical genetics

Published Date

2023/12/1

BackgroundPolygenic risk score (PRS), calculated based on genome-wide association studies (GWASs), can improve breast cancer (BC) risk assessment. To date, most BC GWASs have been performed in individuals of European (EUR) ancestry, and the generalisation of EUR-based PRS to other populations is a major challenge. In this study, we examined the performance of EUR-based BC PRS models in Ashkenazi Jewish (AJ) women.MethodsWe generated PRSs based on data on EUR women from the Breast Cancer Association Consortium (BCAC). We tested the performance of the PRSs in a cohort of 2161 AJ women from Israel (1437 cases and 724 controls) from BCAC (BCAC cohort from Israel (BCAC-IL)). In addition, we tested the performance of these EUR-based BC PRSs, as well as the established 313-SNP EUR BC PRS, in an independent cohort of 181 AJ women from Hadassah Medical Center …

Increased FOXJ1 protein expression is associated with improved overall survival in high-grade serous ovarian carcinoma: an Ovarian Tumor Tissue Analysis Consortium Study

Authors

Ashley Weir,Eun-Young Kang,Nicola S Meagher,Gregg S Nelson,Prafull Ghatage,Cheng-Han Lee,Marjorie J Riggan,Aleksandra Gentry-Maharaj,Andy Ryan,Naveena Singh,Martin Widschwendter,Jennifer Alsop,Michael S Anglesio,Matthias W Beckmann,Jessica Berger,Christiani Bisinotto,Jessica Boros,Alison H Brand,James D Brenton,Angela Brooks-Wilson,Michael E Carney,Julie M Cunningham,Kara L Cushing-Haugen,Cezary Cybulski,Esther Elishaev,Ramona Erber,Sian Fereday,Anna Fischer,Luis Paz-Ares,Javier Gayarre,Blake C Gilks,Marcel Grube,Paul R Harnett,Holly R Harris,Arndt Hartmann,Alexander Hein,Joy Hendley,Brenda Y Hernandez,Sabine Heublein,Yajue Huang,Tomasz Huzarski,Anna Jakubowska,Mercedes Jimenez-Linan,Catherine J Kennedy,Felix KF Kommoss,Jennifer M Koziak,Bernhard Kraemer,Nhu D Le,Jaime Lesnock,Jenny Lester,Jan Lubiński,Janusz Menkiszak,Britta Ney,Alexander Olawaiye,Sandra Orsulic,Ana Osorio,Luis Robles-Díaz,Matthias Ruebner,Mitul Shah,Raghwa Sharma,Yurii B Shvetsov,Helen Steed,Aline Talhouk,Sarah E Taylor,Nadia Traficante,Robert A Vierkant,Chen Wang,Lynne R Wilkens,Stacey J Winham,Javier Benitez,Andrew Berchuck,David D Bowtell,Francisco J Candido dos Reis,Linda S Cook,Anna DeFazio,AOCs group Bowtell D. 30 31 DeFazio A. 5 19 20 21 Traficante N. 30 31 Fereday S. 30 31 Brand A. 20 21 Harnett P. 21 38 Sharma R. 52,Jennifer A Doherty,Peter A Fasching,María J García,Ellen L Goode,Marc T Goodman,Jacek Gronwald,David G Huntsman,Beth Y Karlan,Stefan Kommoss,Francesmary Modugno,Joellen M Schildkraut,Hans-Peter Sinn,Annette Staebler,Linda E Kelemen,Caroline E Ford,Usha Menon,Paul DP Pharoah,Martin Köbel,Susan J Ramus

Journal

British journal of cancer

Published Date

2023/1/26

BackgroundRecently, we showed a >60% difference in 5-year survival for patients with tubo-ovarian high-grade serous carcinoma (HGSC) when stratified by a 101-gene mRNA expression prognostic signature. Given the varied patient outcomes, this study aimed to translate prognostic mRNA markers into protein expression assays by immunohistochemistry and validate their survival association in HGSC.MethodsTwo prognostic genes, FOXJ1 and GMNN, were selected based on high-quality antibodies, correlation with protein expression and variation in immunohistochemical scores in a preliminary cohort (n = 134 and n = 80, respectively). Six thousand four hundred and thirty-four (FOXJ1) and 5470 (GMNN) formalin-fixed, paraffin-embedded ovarian neoplasms (4634 and 4185 HGSC, respectively) represented on tissue microarrays from the Ovarian Tumor Tissue Analysis consortium underwent …

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 …

Rare germline genetic variation in PAX8 transcription factor binding sites and susceptibility to epithelial ovarian cancer

Authors

Suzana AM Ezquina,Michelle Jones,Ed Dicks,Amber de Vries,Pei-Chen Peng,Kate Lawrenson,Rosario I Corona,Jonthan Tyrer,Dennis Hazelett,James Brenton,Antonis Antoniou,Simon A Gayther,Paul DP Pharoah

Journal

medRxiv

Published Date

2023/3/22

Common genetic variation throughout the genome together with rare coding variants identified to date explain about a half of the inherited genetic component of epithelial ovarian cancer risk. It is likely that rare variation in the non-coding genome will explain some of the unexplained heritability, but identifying such variants is challenging. The primary problem is lack of statistical power to identifying individual risk variants by association as power is a function of sample size, effect size and allele frequency. Power can be increased by using burden tests which test for association of carriers of any variant in a specified genomic region. This has the effect of increasing the putative effect allele frequency.PAX8 is a transcription factor that plays a critical role in tumour progression, migration and invasion. Furthermore, regulatory elements proximal to target genes of PAX8 are enriched for common ovarian cancer risk variants. We hypothesised that rare variation in PAX8 binding sites are also associated with ovarian cancer risk, but unlikely to be associated with risk of breast, colorectal or endometrial cancer.We have used publicly-available, whole-genome sequencing data from the UK 100,000 Genomes Project to evaluate the burden of rare variation in PAX8 binding sites across the genome. Data were available for 522 ovarian cancers, 2560 breast cancers, 2465 colorectal cancers and 729 endometrial cancers and 2253 non-cancer controls. Active binding sites were defined using data from multiple PAX8 and H3K27 ChIPseq experiments.We found no association between the burden of rare variation in PAX8 binding sites (defined in several ways) and …

CCNE1 and survival of patients with tubo‐ovarian high‐grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study

Authors

Eun‐Young Kang,Ashley Weir,Nicola S Meagher,Kyo Farrington,Gregg S Nelson,Prafull Ghatage,Cheng‐Han Lee,Marjorie J Riggan,Adelyn Bolithon,Gordana Popovic,Betty Leung,Katrina Tang,Neil Lambie,Joshua Millstein,Jennifer Alsop,Michael S Anglesio,Beyhan Ataseven,Ellen Barlow,Matthias W Beckmann,Jessica Berger,Christiani Bisinotto,Hans Bösmüller,Jessica Boros,Alison H Brand,Angela Brooks‐Wilson,Sara Y Brucker,Michael E Carney,Yovanni Casablanca,Alicia Cazorla‐Jiménez,Paul A Cohen,Thomas P Conrads,Linda S Cook,Penny Coulson,Madeleine Courtney‐Brooks,Daniel W Cramer,Philip Crowe,Julie M Cunningham,Cezary Cybulski,Kathleen M Darcy,Mona A El‐Bahrawy,Esther Elishaev,Ramona Erber,Rhonda Farrell,Sian Fereday,Anna Fischer,María J García,Simon A Gayther,Aleksandra Gentry‐Maharaj,C Blake Gilks,AOCS Group,Marcel Grube,Paul R Harnett,Shariska Petersen Harrington,Philipp Harter,Arndt Hartmann,Jonathan L Hecht,Sebastian Heikaus,Alexander Hein,Florian Heitz,Joy Hendley,Brenda Y Hernandez,Susanna Hernando Polo,Sabine Heublein,Akira Hirasawa,Estrid Høgdall,Claus K Høgdall,Hugo M Horlings,David G Huntsman,Tomasz Huzarski,Andrea Jewell,Mercedes Jimenez‐Linan,Michael E Jones,Scott H Kaufmann,Catherine J Kennedy,Dineo Khabele,Felix KF Kommoss,Roy FPM Kruitwagen,Diether Lambrechts,Nhu D Le,Marcin Lener,Jenny Lester,Yee Leung,Anna Linder,Liselore Loverix,Jan Lubiński,Rashna Madan,G Larry Maxwell,Francesmary Modugno,Susan L Neuhausen,Alexander Olawaiye,Siel Olbrecht,Sandra Orsulic,José Palacios,Celeste Leigh Pearce,Malcolm C Pike,Carmel M Quinn,Ganendra Raj Mohan,Cristina Rodríguez‐Antona,Matthias Ruebner,Andy Ryan,Stuart G Salfinger,Naoko Sasamoto,Joellen M Schildkraut,Minouk J Schoemaker,Mitul Shah,Raghwa Sharma,Yurii B Shvetsov,Naveena Singh,Gabe S Sonke,Linda Steele,Colin JR Stewart,Karin Sundfeldt,Anthony J Swerdlow,Aline Talhouk,Adeline Tan,Sarah E Taylor,Kathryn L Terry,Aleksandra Tołoczko,Nadia Traficante,Koen K Van de Vijver,Maaike A van der Aa,Toon Van Gorp,Els Van Nieuwenhuysen,Lilian van‐Wagensveld,Ignace Vergote,Robert A Vierkant,Chen Wang,Lynne R Wilkens,Stacey J Winham,Anna H Wu,Javier Benitez,Andrew Berchuck,Francisco J Candido dos Reis,Anna DeFazio,Peter A Fasching,Ellen L Goode,Marc T Goodman,Jacek Gronwald,Beth Y Karlan,Stefan Kommoss,Usha Menon,Hans‐Peter Sinn,Annette Staebler,James D Brenton,David D Bowtell,Paul DP Pharoah,Susan J Ramus,Martin Köbel

Journal

Cancer

Published Date

2023/3/1

Background Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo‐ovarian high‐grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large‐scale, histotype‐specific validation has been performed. The hypothesis was that high‐level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. Methods Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. Results High‐level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found …

Cross-trait genome-wide association meta-analyses of clonal hematopoiesis and solid tumor risk

Authors

Victoria Gray,George Richenberg,Pedro Quirós,Matthew Freedman,Paul Pharoah,Simon Gayther,Michelle Jones,George Vassiliou,Kate Lawrenson,Siddhartha Kar

Journal

Cancer Research

Published Date

2023/4/4

Clonal hematopoiesis (CH) is an age-related phenomenon where hematopoietic stem cells and their progeny acquire specific somatic mutations in a small, well-defined set of leukemogenic genes conferring them with fitness advantage leading to clonal proliferation. Mosaic chromosomal alterations (mCAs) are somatic structural variants that are manifestations of genomic instability and a sign of CH when they occur in blood. The recent availability of large-scale cohorts with blood exome sequence and genotype data has powered genome-wide association studies (GWAS) investigating the germline genetic contribution to CH and mCA risk. However, phenotypes of somatic mutation acquisition in driver genes, clonal selection and expansion, and chromosomal mosaicism are processes that are not confined to blood and contribute to neoplastic transformation across tissue types. GWAS of solid tumor susceptibility …

Lifestyle and personal factors associated with having macroscopic residual disease after ovarian cancer primary cytoreductive surgery

Authors

Minh Tung Phung,Penelope M Webb,Anna DeFazio,Sian Fereday,Alice W Lee,David DL Bowtell,Peter A Fasching,Ellen L Goode,Marc T Goodman,Beth Y Karlan,Jenny Lester,Keitaro Matsuo,Francesmary Modugno,James D Brenton,Toon Van Gorp,Paul DP Pharoah,Joellen M Schildkraut,Karen McLean,Rafael Meza,Bhramar Mukherjee,Jean Richardson,Bronwyn Grout,Anne Chase,Cindy McKinnon Deurloo,Kathryn L Terry,Gillian E Hanley,Malcolm C Pike,Andrew Berchuck,Susan J Ramus,Celeste Leigh Pearce,Ovarian Cancer Association Consortium

Journal

Gynecologic oncology

Published Date

2023/1/1

ObjectiveThe presence of macroscopic residual disease after primary cytoreductive surgery (PCS) is an important factor influencing survival for patients with high-grade serous ovarian cancer (HGSC). More research is needed to identify factors associated with having macroscopic residual disease. We analyzed 12 lifestyle and personal exposures known to be related to ovarian cancer risk or inflammation to identify those associated with having residual disease after surgery.MethodsThis analysis used data on 2054 patients with advanced stage HGSC from the Ovarian Cancer Association Consortium. The exposures were body mass index, breastfeeding, oral contraceptive use, depot-medroxyprogesterone acetate use, endometriosis, first-degree family history of ovarian cancer, incomplete pregnancy, menopausal hormone therapy use, menopausal status, parity, smoking, and tubal ligation. Logistic regression …

A framework for assessing interactions for risk stratification models: the example of ovarian cancer

Authors

Minh Tung Phung,Alice W Lee,Karen McLean,Hoda Anton-Culver,Elisa V Bandera,Michael E Carney,Jenny Chang-Claude,Daniel W Cramer,Jennifer Anne Doherty,Renee T Fortner,Marc T Goodman,Holly R Harris,Allan Jensen,Francesmary Modugno,Kirsten B Moysich,Paul DP Pharoah,Bo Qin,Kathryn L Terry,Linda J Titus,Penelope M Webb,Anna H Wu,Nur Zeinomar,Argyrios Ziogas,Andrew Berchuck,Kathleen R Cho,Gillian E Hanley,Rafael Meza,Bhramar Mukherjee,Malcolm C Pike,Celeste Leigh Pearce,Britton Trabert

Journal

JNCI: Journal of the National Cancer Institute

Published Date

2023/11/1

Generally, risk stratification models for cancer use effect estimates from risk/protective factor analyses that have not assessed potential interactions between these exposures. We have developed a 4-criterion framework for assessing interactions that includes statistical, qualitative, biological, and practical approaches. We present the application of this framework in an ovarian cancer setting because this is an important step in developing more accurate risk stratification models. Using data from 9 case-control studies in the Ovarian Cancer Association Consortium, we conducted a comprehensive analysis of interactions among 15 unequivocal risk and protective factors for ovarian cancer (including 14 non-genetic factors and a 36-variant polygenic score) with age and menopausal status. Pairwise interactions between the risk/protective factors were also assessed. We found that menopausal status modifies the …

Impact of PARP Inhibitor and Platinum Therapy on Clonal Hematopoiesis

Authors

Jeremy T Baeten,Irenaeus CC Chan,Lea Moukarzel,Amber C Carter,Minal Patel,Konrad H Stopsack,Paul Pharoah,James Brenton,Bob T Li,Wassim Abida,Alison M Schram,Karen Cadoo,Britta Weigelt,Carlos Cruchaga,Howard Scher,Ross L Levine,Elli Papaemmanuil,Daniel C Link,Kelly L Bolton

Journal

Blood

Published Date

2023/11/28

Poly (ADP-ribose) polymerase inhibitors (PARPi) are a promising new class of targeted therapy used in a variety of solid tumors with homologous recombination deficiencies (HRD). Data from clinical trials and observational studies have linked PARPi and platinum-based agents to therapy-related myeloid neoplasia (tMN). However, interpretation of these findings is limited by confounding variables including germline mutation status and prior therapeutic exposure. We and others have shown that the oncologic therapies known to confer an elevated risk of leukemia also promote the expansion of clonal hematopoiesis (CH) due to mutations of genes in the DNA damage response (DDR) pathway, including TP53, PPM1D and CHEK2. However, the extent to which CH is associated with targeted therapies such as PARPi is not clear. We hypothesized that exposure to PARPi confers a competitive advantage to …

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 …

Polygenic scores in cancer

Authors

Xin Yang,Siddhartha Kar,Antonis C Antoniou,Paul DP Pharoah

Published Date

2023/9

Authors

Journal

medRxiv

Published Date

2022/10/26

Aims/hypothesisEpidemiological studies have generated conflicting findings on the relationship between anti-diabetic medication use and cancer risk. Naturally occurring variation in genes encoding anti-diabetic drug targets can be used to investigate the effect of their pharmacological perturbation on cancer risk.MethodsWe developed genetic instruments for three anti-diabetic drug targets (peroxisome proliferator activated receptor gamma, PPARG; sulfonylurea receptor 1, ABCC8; glucagon-like peptide 1 receptor, GLP1R) using summary genetic association data from a genome-wide association study (GWAS) of type 2 diabetes in 69,869 cases and 127,197 controls in the Million Veteran Program. Genetic instruments were constructed using cis-acting genome-wide significant (P<5×10−8) single-nucleotide polymorphisms (SNPs) permitted to be in weak linkage disequilibrium (r2<0.20). Summary genetic association estimates for these SNPs were obtained from GWAS consortia for the following cancers: breast (122,977 cases, 105,974 controls), colorectal (58,221 cases, 67,694 controls), prostate (79,148 cases, 61,106 controls), and overall (i.e. site-combined) cancer (27,483 cases, 372,016 controls). Inverse-variance weighted random-effects models adjusting for linkage disequilibrium were employed to estimate causal associations between genetically-proxied drug target perturbation and cancer risk. Colocalisation analysis was employed to examine robustness of findings to violations of Mendelian randomization (MR) assumptions. A Bonferroni correction was employed as a heuristic to define associations from MR analyses as “strong” and …

Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Authors

Thomas U Ahearn,Haoyu Zhang,Kyriaki Michailidou,Roger L Milne,Manjeet K Bolla,Joe Dennis,Alison M Dunning,Michael Lush,Qin Wang,Irene L Andrulis,Hoda Anton-Culver,Volker Arndt,Kristan J Aronson,Paul L Auer,Annelie Augustinsson,Adinda Baten,Heiko Becher,Sabine Behrens,Javier Benitez,Marina Bermisheva,Carl Blomqvist,Stig E Bojesen,Bernardo Bonanni,Anne-Lise Børresen-Dale,Hiltrud Brauch,Hermann Brenner,Angela Brooks-Wilson,Thomas Brüning,Barbara Burwinkel,Saundra S Buys,Federico Canzian,Jose E Castelao,Jenny Chang-Claude,Stephen J Chanock,Georgia Chenevix-Trench,Christine L Clarke,J Margriet Collée,Angela Cox,Simon S Cross,Kamila Czene,Mary B Daly,Peter Devilee,Thilo Dörk,Miriam Dwek,Diana M Eccles,D Gareth Evans,Peter A Fasching,Jonine Figueroa,Giuseppe Floris,Manuela Gago-Dominguez,Susan M Gapstur,José A García-Sáenz,Mia M Gaudet,Graham G Giles,Mark S Goldberg,Anna González-Neira,Grethe I Grenaker Alnæs,Mervi Grip,Pascal Guénel,Christopher A Haiman,Per Hall,Ute Hamann,Elaine F Harkness,Bernadette AM Heemskerk-Gerritsen,Bernd Holleczek,Antoinette Hollestelle,Maartje J Hooning,Robert N Hoover,John L Hopper,Anthony Howell,kConFab/AOCS Investigators Stephen Fox Ian Campbell David Bowtell Georgia Chenevix-Trench Amanda Spurdle Penny Webb Anna de Fazio Margaret Tassell Judy Kirk Geoff Lindeman Melanie Price Melissa Southey Roger Milne Sid Deb,Milena Jakimovska,Anna Jakubowska,Esther M John,Michael E Jones,Audrey Jung,Rudolf Kaaks,Saila Kauppila,Renske Keeman,Elza Khusnutdinova,Cari M Kitahara,Yon-Dschun Ko,Stella Koutros,Vessela N Kristensen,Ute Krüger,Katerina Kubelka-Sabit,Allison W Kurian,Kyriacos Kyriacou,Diether Lambrechts,Derrick G Lee,Annika Lindblom,Martha Linet,Jolanta Lissowska,Ana Llaneza,Wing-Yee Lo,Robert J MacInnis,Arto Mannermaa,Mehdi Manoochehri,Sara Margolin,Maria Elena Martinez,Catriona McLean,Alfons Meindl,Usha Menon,Heli Nevanlinna,William G Newman,Jesse Nodora,Kenneth Offit,Håkan Olsson,Nick Orr,Tjoung-Won Park-Simon,Alpa V Patel,Julian Peto,Guillermo Pita,Dijana Plaseska-Karanfilska,Ross Prentice,Kevin Punie,Katri Pylkäs,Paolo Radice,Gad Rennert,Atocha Romero,Thomas Rüdiger,Emmanouil Saloustros,Sarah Sampson,Dale P Sandler,Elinor J Sawyer,Rita K Schmutzler,Minouk J Schoemaker,Ben Schöttker,Mark E Sherman,Xiao-Ou Shu,Snezhana Smichkoska,Melissa C Southey,John J Spinelli,Anthony J Swerdlow,Rulla M Tamimi,William J Tapper,Jack A Taylor,Lauren R Teras,Mary Beth Terry,Diana Torres,Melissa A Troester,Celine M Vachon,Carolien HM van Deurzen,Elke M van Veen,Philippe Wagner,Clarice R Weinberg,Camilla Wendt,Jelle Wesseling

Journal

Breast Cancer Research

Published Date

2022/12

Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results Eighty-five of 173 variants were associated with at least one tumor …

Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci

Authors

Hongjie Chen,Shaoqi Fan,Jennifer Stone,Deborah J Thompson,Julie Douglas,Shuai Li,Christopher Scott,Manjeet K Bolla,Qin Wang,Joe Dennis,Kyriaki Michailidou,Christopher Li,Ulrike Peters,John L Hopper,Melissa C Southey,Tu Nguyen-Dumont,Tuong L Nguyen,Peter A Fasching,Annika Behrens,Gemma Cadby,Rachel A Murphy,Kristan Aronson,Anthony Howell,Susan Astley,Fergus Couch,Janet Olson,Roger L Milne,Graham G Giles,Christopher A Haiman,Gertraud Maskarinec,Stacey Winham,Esther M John,Allison Kurian,Heather Eliassen,Irene Andrulis,D Gareth Evans,William G Newman,Per Hall,Kamila Czene,Anthony Swerdlow,Michael Jones,Marina Pollan,Pablo Fernandez-Navarro,Daniel S McConnell,Vessela N Kristensen,NBCS Investigators,Joseph H Rothstein,Pei Wang,Laurel A Habel,Weiva Sieh,Alison M Dunning,Paul DP Pharoah,Douglas F Easton,Gretchen L Gierach,Rulla M Tamimi,Celine M Vachon,Sara Lindström

Journal

Breast Cancer Research

Published Date

2022/4/12

BackgroundMammographic density (MD) phenotypes, including percent density (PMD), area of dense tissue (DA), and area of non-dense tissue (NDA), are associated with breast cancer risk. Twin studies suggest that MD phenotypes are highly heritable. However, only a small proportion of their variance is explained by identified genetic variants. MethodsWe conducted a genome-wide association study, as well as a transcriptome-wide association study (TWAS), of age- and BMI-adjusted DA, NDA, and PMD in up to 27,900 European-ancestry women from the MODE/BCAC consortia. ResultsWe identified 28 genome-wide significant loci for MD phenotypes, including nine novel signals (5q11.2, 5q14.1, 5q31.1, 5q33.3, 5q35.1, 7p11.2, 8q24.13, 12p11.2, 16q12.2). Further, 45% of all known breast cancer SNPs were associated with at least one MD phenotype at p < 0.05. TWAS further identified two novel genes …

Germline BRCA variants, lifestyle and ovarian cancer survival

Authors

Kate Gersekowski,Rachel Delahunty,Kathryn Alsop,Ellen L Goode,Julie M Cunningham,Stacey J Winham,Paul Pharoah,Honglin Song,Susan Jordan,Sian Fereday,Anna DeFazio,Michael Friedlander,Andreas Obermair,Penelope M Webb,OPAL Study Group,AOCS Group

Journal

Gynecologic oncology

Published Date

2022/6/1

Authors

Elinor Zhou,Lin Wang,Celina N Santiago,Julie Nanavati,Samara Rifkin,Emma Spence,Linda M Hylind,Joell J Gills,Louis La Luna,David R Kafonek,David M Cromwell,Julia L Drewes,Cynthia L Sears,Francis M Giardiello,Gerard E Mullin,Biofilm Study Consortium

Published Date

2022/4/1

Background The influence of anthropometric characteristics on colorectal neoplasia biology is unclear. We conducted a systematic review and meta-analysis to determine if adult-attained height is independently associated with the risk of colorectal cancer or adenoma. Methods We searched MEDLINE, EMBASE, the Cochrane Library, and Web of Science from inception to August 2020 for studies on the association between adult-attained height and colorectal cancer or adenoma. The original data from the Johns Hopkins (Baltimore, MD) Colon Biofilm study was also included. The overall HR/OR of colorectal cancer/adenoma with increased height was estimated using random-effects meta-analysis. Results We included 47 observational studies involving 280,644 colorectal cancer and 14,139 colorectal adenoma cases. Thirty-three studies reported data for …

Breast cancer risks associated with missense variants in breast cancer susceptibility genes

Authors

Leila Dorling,Sara Carvalho,Jamie Allen,Michael T Parsons,Cristina Fortuno,Anna González-Neira,Stephan M Heijl,Muriel A Adank,Thomas U Ahearn,Irene L Andrulis,Päivi Auvinen,Heiko Becher,Matthias W Beckmann,Sabine Behrens,Marina Bermisheva,Natalia V Bogdanova,Stig E Bojesen,Manjeet K Bolla,Michael Bremer,Ignacio Briceno,Nicola J Camp,Archie Campbell,Jose E Castelao,Jenny Chang-Claude,Stephen J Chanock,Georgia Chenevix-Trench,NBCS Collaborators,J Margriet Collée,Kamila Czene,Joe Dennis,Thilo Dörk,Mikael Eriksson,D Gareth Evans,Peter A Fasching,Jonine Figueroa,Henrik Flyger,Marike Gabrielson,Manuela Gago-Dominguez,Montserrat García-Closas,Graham G Giles,Gord Glendon,Pascal Guénel,Melanie Gündert,Andreas Hadjisavvas,Eric Hahnen,Per Hall,Ute Hamann,Elaine F Harkness,Mikael Hartman,Frans BL Hogervorst,Antoinette Hollestelle,Reiner Hoppe,Anthony Howell,kConFab Investigators,SGBCC Investigators,Anna Jakubowska,Audrey Jung,Elza Khusnutdinova,Sung-Won Kim,Yon-Dschun Ko,Vessela N Kristensen,Inge MM Lakeman,Jingmei Li,Annika Lindblom,Maria A Loizidou,Artitaya Lophatananon,Jan Lubiński,Craig Luccarini,Michael J Madsen,Arto Mannermaa,Mehdi Manoochehri,Sara Margolin,Dimitrios Mavroudis,Roger L Milne,Nur Aishah Mohd Taib,Kenneth Muir,Heli Nevanlinna,William G Newman,Jan C Oosterwijk,Sue K Park,Paolo Peterlongo,Paolo Radice,Emmanouil Saloustros,Elinor J Sawyer,Rita K Schmutzler,Mitul Shah,Xueling Sim,Melissa C Southey,Harald Surowy,Maija Suvanto,Ian Tomlinson,Diana Torres,Thérèse Truong,Christi J van Asperen,Regina Waltes,Qin Wang,Xiaohong R Yang,Paul DP Pharoah,Marjanka K Schmidt,Javier Benitez,Bas Vroling,Alison M Dunning,Soo Hwang Teo,Anders Kvist,Miguel de la Hoya,Peter Devilee,Amanda B Spurdle,Maaike PG Vreeswijk,Douglas F Easton

Journal

Genome medicine

Published Date

2022/5/18

BackgroundProtein truncating variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are associated with increased breast cancer risk, but risks associated with missense variants in these genes are uncertain.MethodsWe analyzed data on 59,639 breast cancer cases and 53,165 controls from studies participating in the Breast Cancer Association Consortium BRIDGES project. We sampled training (80%) and validation (20%) sets to analyze rare missense variants in ATM (1146 training variants), BRCA1 (644), BRCA2 (1425), CHEK2 (325), and PALB2 (472). We evaluated breast cancer risks according to five in silico prediction-of-deleteriousness algorithms, functional protein domain, and frequency, using logistic regression models and also mixture models in which a subset of variants was assumed to be risk-associated.ResultsThe most predictive in silico algorithms were Helix (BRCA1, BRCA2 and CHEK2) and …

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

Authors

Andrew Lee,Xin Yang,Jonathan Tyrer,Aleksandra Gentry-Maharaj,Andy Ryan,Nasim Mavaddat,Alex P Cunningham,Tim Carver,Stephanie Archer,Goska Leslie,Jatinder Kalsi,Faiza Gaba,Ranjit Manchanda,Simon Gayther,Susan J Ramus,Fiona M Walter,Marc Tischkowitz,Ian Jacobs,Usha Menon,Douglas F Easton,Paul Pharoah,Antonis C Antoniou

Journal

Journal of Medical Genetics

Published Date

2021/11/21

BackgroundEpithelial 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.MethodsWe 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.ResultsBased 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 …

Incorporating progesterone receptor expression into the PREDICT breast prognostic model

Authors

Isabelle Grootes,Renske Keeman,Fiona M Blows,Roger L Milne,Graham G Giles,Anthony J Swerdlow,Peter A Fasching,Mustapha Abubakar,Irene L Andrulis,Hoda Anton-Culver,Matthias W Beckmann,Carl Blomqvist,Stig E Bojesen,Manjeet K Bolla,Bernardo Bonanni,Ignacio Briceno,Barbara Burwinkel,Nicola J Camp,Jose E Castelao,Ji-Yeob Choi,Christine L Clarke,Fergus J Couch,Angela Cox,Simon S Cross,Kamila Czene,Peter Devilee,Thilo Dörk,Alison M Dunning,Miriam Dwek,Douglas F Easton,Diana M Eccles,Mikael Eriksson,Kristina Ernst,D Gareth Evans,Jonine D Figueroa,Visnja Fink,Giuseppe Floris,Stephen Fox,Marike Gabrielson,Manuela Gago-Dominguez,Jose A Garcia-Saenz,Anna Gonzalez-Neira,Lothar Haeberle,Christopher A Haiman,Per Hall,Ute Hamann,Elaine F Harkness,Mikael Hartman,Alexander Hein,Maartje J Hooning,Ming-Feng Hou,Sacha J Howell,Hidemi Ito,Anna Jakubowska,Wolfgang Janni,Esther M John,Audrey Jung,Daehee Kang,Vessela N Kristensen,Ava Kwong,Diether Lambrechts,Jingmei Li,Jan Lubiński,Mehdi Manoochehri,Sara Margolin,Keitaro Matsuo,Nur Aishah Mohd Taib,Anna Marie Mulligan,Heli Nevanlinna,William G Newman,Kenneth Offit,Ana Osorio,Sue K Park,Tjoung-Won Park-Simon,Alpa V Patel,Nadege Presneau,Katri Pylkäs,Brigitte Rack,Paolo Radice,Gad Rennert,Atocha Romero,Emmanouil Saloustros,Elinor J Sawyer,Andreas Schneeweiss,Fabienne Schochter,Minouk J Schoemaker,Chen-Yang Shen,Rana Shibli,Peter Sinn,William J Tapper,Essa Tawfiq,Soo Hwang Teo,Lauren R Teras,Diana Torres,Celine M Vachon,Carolien HM van Deurzen,Camilla Wendt,Justin A Williams,Robert Winqvist,Mark Elwood,Marjanka K Schmidt,Montserrat García-Closas,Paul DP Pharoah,ABCTB Investigators,kConFab Investigators

Journal

European Journal of Cancer

Published Date

2022/9/1

BackgroundPredict Breast (www.predict.nhs.uk) is an online prognostication and treatment benefit tool for early invasive breast cancer. The aim of this study was to incorporate the prognostic effect of progesterone receptor (PR) status into a new version of PREDICT and to compare its performance to the current version (2.2).MethodThe prognostic effect of PR status was based on the analysis of data from 45,088 European patients with breast cancer from 49 studies in the Breast Cancer Association Consortium. Cox proportional hazard models were used to estimate the hazard ratio for PR status. Data from a New Zealand study of 11,365 patients with early invasive breast cancer were used for external validation. Model calibration and discrimination were used to test the model performance.ResultsHaving a PR-positive tumour was associated with a 23% and 28% lower risk of dying from breast cancer for women with …

Distinct reproductive risk profiles for intrinsic-like breast cancer subtypes: pooled analysis of population-based studies

Authors

Audrey Y Jung,Thomas U Ahearn,Sabine Behrens,Pooja Middha,Manjeet K Bolla,Qin Wang,Volker Arndt,Kristan J Aronson,Annelie Augustinsson,Laura E Beane Freeman,Heiko Becher,Hermann Brenner,Federico Canzian,Lisa A Carey,CTS Consortium,Kamila Czene,A Heather Eliassen,Mikael Eriksson,D Gareth Evans,Jonine D Figueroa,Lin Fritschi,Marike Gabrielson,Graham G Giles,Pascal Guénel,Andreas Hadjisavvas,Christopher A Haiman,Niclas Håkansson,Per Hall,Ute Hamann,Reiner Hoppe,John L Hopper,Anthony Howell,David J Hunter,Anika Hüsing,Rudolf Kaaks,Veli-Matti Kosma,Stella Koutros,Peter Kraft,James V Lacey,Loic Le Marchand,Jolanta Lissowska,Maria A Loizidou,Arto Mannermaa,Tabea Maurer,Rachel A Murphy,Andrew F Olshan,Håkan Olsson,Alpa V Patel,Charles M Perou,Gad Rennert,Rana Shibli,Xiao-Ou Shu,Melissa C Southey,Jennifer Stone,Rulla M Tamimi,Lauren R Teras,Melissa A Troester,Thérèse Truong,Celine M Vachon,Sophia S Wang,Alicja Wolk,Anna H Wu,Xiaohong R Yang,Wei Zheng,Alison M Dunning,Paul DP Pharoah,Douglas F Easton,Roger L Milne,Nilanjan Chatterjee,Marjanka K Schmidt,Montserrat García-Closas,Jenny Chang-Claude

Journal

JNCI: Journal of the National Cancer Institute

Published Date

2022/12/1

Background Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER)-positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear. Methods Analyses included up to 23 353 cases and 71 072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2–like, HER2-enriched–like, and triple-negative breast cancer) and by invasiveness. All statistical tests were 2-sided. Results Compared with nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like …

Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study

Authors

Suzanne C Dixon-Suen,Sarah J Lewis,Richard M Martin,Dallas R English,Terry Boyle,Graham G Giles,Kyriaki Michailidou,Manjeet K Bolla,Qin Wang,Joe Dennis,Michael Lush,Thomas U Ahearn,Christine B Ambrosone,Irene L Andrulis,Hoda Anton-Culver,Volker Arndt,Kristan J Aronson,Annelie Augustinsson,Päivi Auvinen,Laura E Beane Freeman,Heiko Becher,Matthias W Beckmann,Sabine Behrens,Marina Bermisheva,Carl Blomqvist,Natalia V Bogdanova,Stig E Bojesen,Bernardo Bonanni,Hermann Brenner,Thomas Brüning,Saundra S Buys,Nicola J Camp,Daniele Campa,Federico Canzian,Jose E Castelao,Melissa H Cessna,Jenny Chang-Claude,Stephen J Chanock,Christine L Clarke,Don M Conroy,Fergus J Couch,Angela Cox,Simon S Cross,Kamila Czene,Mary B Daly,Peter Devilee,Thilo Dörk,Miriam Dwek,Diana M Eccles,A Heather Eliassen,Christoph Engel,Mikael Eriksson,D Gareth Evans,Peter A Fasching,Olivia Fletcher,Henrik Flyger,Lin Fritschi,Marike Gabrielson,Manuela Gago-Dominguez,Montserrat García-Closas,José A García-Sáenz,Mark S Goldberg,Pascal Guénel,Melanie Gündert,Eric Hahnen,Christopher A Haiman,Lothar Häberle,Niclas Håkansson,Per Hall,Ute Hamann,Steven N Hart,Michelle Harvie,Peter Hillemanns,Antoinette Hollestelle,Maartje J Hooning,Reiner Hoppe,John Hopper,Anthony Howell,David J Hunter,Anna Jakubowska,Wolfgang Janni,Esther M John,Audrey Jung,Rudolf Kaaks,Renske Keeman,Cari M Kitahara,Stella Koutros,Peter Kraft,Vessela N Kristensen,Katerina Kubelka-Sabit,Allison W Kurian,James V Lacey,Diether Lambrechts,Loic Le Marchand,Annika Lindblom,Sibylle Loibl,Jan Lubiński,Arto Mannermaa,Mehdi Manoochehri,Sara Margolin,Maria Elena Martinez,Dimitrios Mavroudis,Usha Menon,Anna Marie Mulligan,Rachel A Murphy,Heli Nevanlinna,Ines Nevelsteen,William G Newman,Kenneth Offit,Andrew F Olshan,Håkan Olsson,Nick Orr,Alpa Patel,Julian Peto,Dijana Plaseska-Karanfilska,Nadege Presneau,Brigitte Rack,Paolo Radice,Erika Rees-Punia,Gad Rennert,Hedy S Rennert,Atocha Romero,Emmanouil Saloustros,Dale P Sandler,Marjanka K Schmidt,Rita K Schmutzler,Lukas Schwentner,Christopher Scott,Mitul Shah,Xiao-Ou Shu,Jacques Simard,Melissa C Southey,Jennifer Stone,Harald Surowy,Anthony J Swerdlow,Rulla M Tamimi,William J Tapper,Jack A Taylor,Mary Beth Terry,Rob AEM Tollenaar,Melissa A Troester,Thérèse Truong,Michael Untch,Celine M Vachon,Vijai Joseph,Barbara Wappenschmidt,Clarice R Weinberg,Alicja Wolk,Drakoulis Yannoukakos,Wei Zheng

Journal

British journal of sports medicine

Published Date

2022/10/1

Authors

Filipa Esteves,Joana M Xavier,Anthony M Ford,Cátia Rocha,Paul DP Pharoah,Carlos Caldas,Suet-Feung Chin,Ana-Teresa Maia

Journal

European Journal of Cancer

Published Date

2022/9/1

HighlightsCase-control analysis using AE as a phenotype detects risk associations.AE of STXBP4 and COX11 in breast tissue and blood associates with BC risk.rs17817901 and rs8066588 are putative cis-regulatory risk-causing variants.Biological risk mechanisms likely involve altered miRNA and protein binding.

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