RT Journal Article
SR Electronic
T1 PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 800
OP 811
DO 10.1136/jmedgenet-2016-103839
VO 53
IS 12
A1 Melissa C Southey
A1 David E Goldgar
A1 Robert Winqvist
A1 Katri Pylkäs
A1 Fergus Couch
A1 Marc Tischkowitz
A1 William D Foulkes
A1 Joe Dennis
A1 Kyriaki Michailidou
A1 Elizabeth J van Rensburg
A1 Tuomas Heikkinen
A1 Heli Nevanlinna
A1 John L Hopper
A1 Thilo Dörk
A1 Kathleen BM Claes
A1 Jorge Reis-Filho
A1 Zhi Ling Teo
A1 Paolo Radice
A1 Irene Catucci
A1 Paolo Peterlongo
A1 Helen Tsimiklis
A1 Fabrice A Odefrey
A1 James G Dowty
A1 Marjanka K Schmidt
A1 Annegien Broeks
A1 Frans B Hogervorst
A1 Senno Verhoef
A1 Jane Carpenter
A1 Christine Clarke
A1 Rodney J Scott
A1 Peter A Fasching
A1 Lothar Haeberle
A1 Arif B Ekici
A1 Matthias W Beckmann
A1 Julian Peto
A1 Isabel dos-Santos-Silva
A1 Olivia Fletcher
A1 Nichola Johnson
A1 Manjeet K Bolla
A1 Elinor J Sawyer
A1 Ian Tomlinson
A1 Michael J Kerin
A1 Nicola Miller
A1 Federik Marme
A1 Barbara Burwinkel
A1 Rongxi Yang
A1 Pascal Guénel
A1 Thérèse Truong
A1 Florence Menegaux
A1 Marie Sanchez
A1 Stig Bojesen
A1 Sune F Nielsen
A1 Henrik Flyger
A1 Javier Benitez
A1 M Pilar Zamora
A1 Jose Ignacio Arias Perez
A1 Primitiva Menéndez
A1 Hoda Anton-Culver
A1 Susan Neuhausen
A1 Argyrios Ziogas
A1 Christina A Clarke
A1 Hermann Brenner
A1 Volker Arndt
A1 Christa Stegmaier
A1 Hiltrud Brauch
A1 Thomas Brüning
A1 Yon-Dschun Ko
A1 Taru A Muranen
A1 Kristiina Aittomäki
A1 Carl Blomqvist
A1 Natalia V Bogdanova
A1 Natalia N Antonenkova
A1 Annika Lindblom
A1 Sara Margolin
A1 Arto Mannermaa
A1 Vesa Kataja
A1 Veli-Matti Kosma
A1 Jaana M Hartikainen
A1 Amanda B Spurdle
A1 kConFab Investigators
A1 Australian Ovarian Cancer Study Group
A1 Els Wauters
A1 Dominiek Smeets
A1 Benoit Beuselinck
A1 Giuseppe Floris
A1 Jenny Chang-Claude
A1 Anja Rudolph
A1 Petra Seibold
A1 Dieter Flesch-Janys
A1 Janet E Olson
A1 Celine Vachon
A1 Vernon S Pankratz
A1 Catriona McLean
A1 Christopher A Haiman
A1 Brian E Henderson
A1 Fredrick Schumacher
A1 Loic Le Marchand
A1 Vessela Kristensen
A1 Grethe Grenaker Alnæs
A1 Wei Zheng
A1 David J Hunter
A1 Sara Lindstrom
A1 Susan E Hankinson
A1 Peter Kraft
A1 Irene Andrulis
A1 Julia A Knight
A1 Gord Glendon
A1 Anna Marie Mulligan
A1 Arja Jukkola-Vuorinen
A1 Mervi Grip
A1 Saila Kauppila
A1 Peter Devilee
A1 Robert A E M Tollenaar
A1 Caroline Seynaeve
A1 Antoinette Hollestelle
A1 Montserrat Garcia-Closas
A1 Jonine Figueroa
A1 Stephen J Chanock
A1 Jolanta Lissowska
A1 Kamila Czene
A1 Hatef Darabi
A1 Mikael Eriksson
A1 Diana M Eccles
A1 Sajjad Rafiq
A1 William J Tapper
A1 Sue M Gerty
A1 Maartje J Hooning
A1 John W M Martens
A1 J Margriet Collée
A1 Madeleine Tilanus-Linthorst
A1 Per Hall
A1 Jingmei Li
A1 Judith S Brand
A1 Keith Humphreys
A1 Angela Cox
A1 Malcolm W R Reed
A1 Craig Luccarini
A1 Caroline Baynes
A1 Alison M Dunning
A1 Ute Hamann
A1 Diana Torres
A1 Hans Ulrich Ulmer
A1 Thomas Rüdiger
A1 Anna Jakubowska
A1 Jan Lubinski
A1 Katarzyna Jaworska
A1 Katarzyna Durda
A1 Susan Slager
A1 Amanda E Toland
A1 Christine B Ambrosone
A1 Drakoulis Yannoukakos
A1 Anthony Swerdlow
A1 Alan Ashworth
A1 Nick Orr
A1 Michael Jones
A1 Anna González-Neira
A1 Guillermo Pita
A1 M Rosario Alonso
A1 Nuria Álvarez
A1 Daniel Herrero
A1 Daniel C Tessier
A1 Daniel Vincent
A1 Francois Bacot
A1 Jacques Simard
A1 Martine Dumont
A1 Penny Soucy
A1 Rosalind Eeles
A1 Kenneth Muir
A1 Fredrik Wiklund
A1 Henrik Gronberg
A1 Johanna Schleutker
A1 Børge G Nordestgaard
A1 Maren Weischer
A1 Ruth C Travis
A1 David Neal
A1 Jenny L Donovan
A1 Freddie C Hamdy
A1 Kay-Tee Khaw
A1 Janet L Stanford
A1 William J Blot
A1 Stephen Thibodeau
A1 Daniel J Schaid
A1 Joseph L Kelley
A1 Christiane Maier
A1 Adam S Kibel
A1 Cezary Cybulski
A1 Lisa Cannon-Albright
A1 Katja Butterbach
A1 Jong Park
A1 Radka Kaneva
A1 Jyotsna Batra
A1 Manuel R Teixeira
A1 Zsofia Kote-Jarai
A1 Ali Amin Al Olama
A1 Sara Benlloch
A1 Stefan P Renner
A1 Arndt Hartmann
A1 Alexander Hein
A1 Matthias Ruebner
A1 Diether Lambrechts
A1 Els Van Nieuwenhuysen
A1 Ignace Vergote
A1 Sandrina Lambretchs
A1 Jennifer A Doherty
A1 Mary Anne Rossing
A1 Stefan Nickels
A1 Ursula Eilber
A1 Shan Wang-Gohrke
A1 Kunle Odunsi
A1 Lara E Sucheston-Campbell
A1 Grace Friel
A1 Galina Lurie
A1 Jeffrey L Killeen
A1 Lynne R Wilkens
A1 Marc T Goodman
A1 Ingo Runnebaum
A1 Peter A Hillemanns
A1 Liisa M Pelttari
A1 Ralf Butzow
A1 Francesmary Modugno
A1 Robert P Edwards
A1 Roberta B Ness
A1 Kirsten B Moysich
A1 Andreas du Bois
A1 Florian Heitz
A1 Philipp Harter
A1 Stefan Kommoss
A1 Beth Y Karlan
A1 Christine Walsh
A1 Jenny Lester
A1 Allan Jensen
A1 Susanne Krüger Kjaer
A1 Estrid Høgdall
A1 Bernard Peissel
A1 Bernardo Bonanni
A1 Loris Bernard
A1 Ellen L Goode
A1 Brooke L Fridley
A1 Robert A Vierkant
A1 Julie M Cunningham
A1 Melissa C Larson
A1 Zachary C Fogarty
A1 Kimberly R Kalli
A1 Dong Liang
A1 Karen H Lu
A1 Michelle A T Hildebrandt
A1 Xifeng Wu
A1 Douglas A Levine
A1 Fanny Dao
A1 Maria Bisogna
A1 Andrew Berchuck
A1 Edwin S Iversen
A1 Jeffrey R Marks
A1 Lucy Akushevich
A1 Daniel W Cramer
A1 Joellen Schildkraut
A1 Kathryn L Terry
A1 Elizabeth M Poole
A1 Meir Stampfer
A1 Shelley S Tworoger
A1 Elisa V Bandera
A1 Irene Orlow
A1 Sara H Olson
A1 Line Bjorge
A1 Helga B Salvesen
A1 Anne M van Altena
A1 Katja K H Aben
A1 Lambertus A Kiemeney
A1 Leon F A G Massuger
A1 Tanja Pejovic
A1 Yukie Bean
A1 Angela Brooks-Wilson
A1 Linda E Kelemen
A1 Linda S Cook
A1 Nhu D Le
A1 Bohdan Górski
A1 Jacek Gronwald
A1 Janusz Menkiszak
A1 Claus K Høgdall
A1 Lene Lundvall
A1 Lotte Nedergaard
A1 Svend Aage Engelholm
A1 Ed Dicks
A1 Jonathan Tyrer
A1 Ian Campbell
A1 Iain McNeish
A1 James Paul
A1 Nadeem Siddiqui
A1 Rosalind Glasspool
A1 Alice S Whittemore
A1 Joseph H Rothstein
A1 Valerie McGuire
A1 Weiva Sieh
A1 Hui Cai
A1 Xiao-Ou Shu
A1 Rachel T Teten
A1 Rebecca Sutphen
A1 John R McLaughlin
A1 Steven A Narod
A1 Catherine M Phelan
A1 Alvaro N Monteiro
A1 David Fenstermacher
A1 Hui-Yi Lin
A1 Jennifer B Permuth
A1 Thomas A Sellers
A1 Y Ann Chen
A1 Ya-Yu Tsai
A1 Zhihua Chen
A1 Aleksandra Gentry-Maharaj
A1 Simon A Gayther
A1 Susan J Ramus
A1 Usha Menon
A1 Anna H Wu
A1 Celeste L Pearce
A1 David Van Den Berg
A1 Malcolm C Pike
A1 Agnieszka Dansonka-Mieszkowska
A1 Joanna Plisiecka-Halasa
A1 Joanna Moes-Sosnowska
A1 Jolanta Kupryjanczyk
A1 Paul DP Pharoah
A1 Honglin Song
A1 Ingrid Winship
A1 Georgia Chenevix-Trench
A1 Graham G Giles
A1 Sean V Tavtigian
A1 Doug F Easton
A1 Roger L Milne
YR 2016
UL http://jmg.bmj.com/content/53/12/800.abstract
AB Background The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study.Methods We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant.Results For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10−5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10−8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants.Conclusions This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.