@article {Southey800, author = {Melissa C Southey and David E Goldgar and Robert Winqvist and Katri Pylk{\"a}s and Fergus Couch and Marc Tischkowitz and William D Foulkes and Joe Dennis and Kyriaki Michailidou and Elizabeth J van Rensburg and Tuomas Heikkinen and Heli Nevanlinna and John L Hopper and Thilo D{\"o}rk and Kathleen BM Claes and Jorge Reis-Filho and Zhi Ling Teo and Paolo Radice and Irene Catucci and Paolo Peterlongo and Helen Tsimiklis and Fabrice A Odefrey and James G Dowty and Marjanka K Schmidt and Annegien Broeks and Frans B Hogervorst and Senno Verhoef and Jane Carpenter and Christine Clarke and Rodney J Scott and Peter A Fasching and Lothar Haeberle and Arif B Ekici and Matthias W Beckmann and Julian Peto and Isabel dos-Santos-Silva and Olivia Fletcher and Nichola Johnson and Manjeet K Bolla and Elinor J Sawyer and Ian Tomlinson and Michael J Kerin and Nicola Miller and Federik Marme and Barbara Burwinkel and Rongxi Yang and Pascal Gu{\'e}nel and Th{\'e}r{\`e}se Truong and Florence Menegaux and Marie Sanchez and Stig Bojesen and Sune F Nielsen and Henrik Flyger and Javier Benitez and M Pilar Zamora and Jose Ignacio Arias Perez and Primitiva Men{\'e}ndez and Hoda Anton-Culver and Susan Neuhausen and Argyrios Ziogas and Christina A Clarke and Hermann Brenner and Volker Arndt and Christa Stegmaier and Hiltrud Brauch and Thomas Br{\"u}ning and Yon-Dschun Ko and Taru A Muranen and Kristiina Aittom{\"a}ki and Carl Blomqvist and Natalia V Bogdanova and Natalia N Antonenkova and Annika Lindblom and Sara Margolin and Arto Mannermaa and Vesa Kataja and Veli-Matti Kosma and Jaana M Hartikainen and Amanda B Spurdle and kConFab Investigators and Australian Ovarian Cancer Study Group and Els Wauters and Dominiek Smeets and Benoit Beuselinck and Giuseppe Floris and Jenny Chang-Claude and Anja Rudolph and Petra Seibold and Dieter Flesch-Janys and Janet E Olson and Celine Vachon and Vernon S Pankratz and Catriona McLean and Christopher A Haiman and Brian E Henderson and Fredrick Schumacher and Loic Le Marchand and Vessela Kristensen and Grethe Grenaker Aln{\ae}s and Wei Zheng and David J Hunter and Sara Lindstrom and Susan E Hankinson and Peter Kraft and Irene Andrulis and Julia A Knight and Gord Glendon and Anna Marie Mulligan and Arja Jukkola-Vuorinen and Mervi Grip and Saila Kauppila and Peter Devilee and Robert A E M Tollenaar and Caroline Seynaeve and Antoinette Hollestelle and Montserrat Garcia-Closas and Jonine Figueroa and Stephen J Chanock and Jolanta Lissowska and Kamila Czene and Hatef Darabi and Mikael Eriksson and Diana M Eccles and Sajjad Rafiq and William J Tapper and Sue M Gerty and Maartje J Hooning and John W M Martens and J Margriet Coll{\'e}e and Madeleine Tilanus-Linthorst and Per Hall and Jingmei Li and Judith S Brand and Keith Humphreys and Angela Cox and Malcolm W R Reed and Craig Luccarini and Caroline Baynes and Alison M Dunning and Ute Hamann and Diana Torres and Hans Ulrich Ulmer and Thomas R{\"u}diger and Anna Jakubowska and Jan Lubinski and Katarzyna Jaworska and Katarzyna Durda and Susan Slager and Amanda E Toland and Christine B Ambrosone and Drakoulis Yannoukakos and Anthony Swerdlow and Alan Ashworth and Nick Orr and Michael Jones and Anna Gonz{\'a}lez-Neira and Guillermo Pita and M Rosario Alonso and Nuria {\'A}lvarez and Daniel Herrero and Daniel C Tessier and Daniel Vincent and Francois Bacot and Jacques Simard and Martine Dumont and Penny Soucy and Rosalind Eeles and Kenneth Muir and Fredrik Wiklund and Henrik Gronberg and Johanna Schleutker and B{\o}rge G Nordestgaard and Maren Weischer and Ruth C Travis and David Neal and Jenny L Donovan and Freddie C Hamdy and Kay-Tee Khaw and Janet L Stanford and William J Blot and Stephen Thibodeau and Daniel J Schaid and Joseph L Kelley and Christiane Maier and Adam S Kibel and Cezary Cybulski and Lisa Cannon-Albright and Katja Butterbach and Jong Park and Radka Kaneva and Jyotsna Batra and Manuel R Teixeira and Zsofia Kote-Jarai and Ali Amin Al Olama and Sara Benlloch and Stefan P Renner and Arndt Hartmann and Alexander Hein and Matthias Ruebner and Diether Lambrechts and Els Van Nieuwenhuysen and Ignace Vergote and Sandrina Lambretchs and Jennifer A Doherty and Mary Anne Rossing and Stefan Nickels and Ursula Eilber and Shan Wang-Gohrke and Kunle Odunsi and Lara E Sucheston-Campbell and Grace Friel and Galina Lurie and Jeffrey L Killeen and Lynne R Wilkens and Marc T Goodman and Ingo Runnebaum and Peter A Hillemanns and Liisa M Pelttari and Ralf Butzow and Francesmary Modugno and Robert P Edwards and Roberta B Ness and Kirsten B Moysich and Andreas du Bois and Florian Heitz and Philipp Harter and Stefan Kommoss and Beth Y Karlan and Christine Walsh and Jenny Lester and Allan Jensen and Susanne Kr{\"u}ger Kjaer and Estrid H{\o}gdall and Bernard Peissel and Bernardo Bonanni and Loris Bernard and Ellen L Goode and Brooke L Fridley and Robert A Vierkant and Julie M Cunningham and Melissa C Larson and Zachary C Fogarty and Kimberly R Kalli and Dong Liang and Karen H Lu and Michelle A T Hildebrandt and Xifeng Wu and Douglas A Levine and Fanny Dao and Maria Bisogna and Andrew Berchuck and Edwin S Iversen and Jeffrey R Marks and Lucy Akushevich and Daniel W Cramer and Joellen Schildkraut and Kathryn L Terry and Elizabeth M Poole and Meir Stampfer and Shelley S Tworoger and Elisa V Bandera and Irene Orlow and Sara H Olson and Line Bjorge and Helga B Salvesen and Anne M van Altena and Katja K H Aben and Lambertus A Kiemeney and Leon F A G Massuger and Tanja Pejovic and Yukie Bean and Angela Brooks-Wilson and Linda E Kelemen and Linda S Cook and Nhu D Le and Bohdan G{\'o}rski and Jacek Gronwald and Janusz Menkiszak and Claus K H{\o}gdall and Lene Lundvall and Lotte Nedergaard and Svend Aage Engelholm and Ed Dicks and Jonathan Tyrer and Ian Campbell and Iain McNeish and James Paul and Nadeem Siddiqui and Rosalind Glasspool and Alice S Whittemore and Joseph H Rothstein and Valerie McGuire and Weiva Sieh and Hui Cai and Xiao-Ou Shu and Rachel T Teten and Rebecca Sutphen and John R McLaughlin and Steven A Narod and Catherine M Phelan and Alvaro N Monteiro and David Fenstermacher and Hui-Yi Lin and Jennifer B Permuth and Thomas A Sellers and Y Ann Chen and Ya-Yu Tsai and Zhihua Chen and Aleksandra Gentry-Maharaj and Simon A Gayther and Susan J Ramus and Usha Menon and Anna H Wu and Celeste L Pearce and David Van Den Berg and Malcolm C Pike and Agnieszka Dansonka-Mieszkowska and Joanna Plisiecka-Halasa and Joanna Moes-Sosnowska and Jolanta Kupryjanczyk and Paul DP Pharoah and Honglin Song and Ingrid Winship and Georgia Chenevix-Trench and Graham G Giles and Sean V Tavtigian and Doug F Easton and Roger L Milne}, title = {PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS}, volume = {53}, number = {12}, pages = {800--811}, year = {2016}, doi = {10.1136/jmedgenet-2016-103839}, publisher = {BMJ Publishing Group Ltd}, abstract = {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{\texttimes}10-5), PALB2 c.3113G\>A OR 4.21 (95\% CI 1.84 to 9.60, p=6.9{\texttimes}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.}, issn = {0022-2593}, URL = {https://jmg.bmj.com/content/53/12/800}, eprint = {https://jmg.bmj.com/content/53/12/800.full.pdf}, journal = {Journal of Medical Genetics} }