PALB2, CHEK2 and ATM rare variants and cancer risk: Data from COGS

Melissa Southey, David E. Goldgar, Robert Winqvist, Katri Pylkäs, Fergus J. Couch, Marc Tischkowitz, W. D. Foulkes, Joe Dennis, Kyriaki Michailidou, Elizabeth J. van Rensburg, Tuomas Heikkinen, Heli Nevanlinna, John Hopper, Thilo Dörk, Kathleen Claes, Jorge S. Reis-Filho, Z. L. Teo, Paolo Radice, Irene Catucci, Paolo PeterlongoHelen Tsimiklis, Fabrice Odefrey, James G. Dowty, Marjanka K. Schmidt, Annegien Broeks, Frans B. Hogervorst, S. Verhoef, Jane Carpenter, Christine Clarke, Rodney J. Scott, Peter A. Fasching, Lothar Haeberle, Arif B. Ekici, Matthias W. Beckmann, Julian Peto, Isabel Dos-Santos-Silva, Olivia Fletcher, Nichola Johnson, Manjeet K. Bolla, Elinor J. Sawyer, Ian Tomlinson, Michael J. Kerin, Nicola Miller, Federik Marme, Barbara Burwinkel, Rongxi Yang, Pascal Guenel, Thérèse Truong, Florence Menegaux, Marie Sanchez, Stig E. Bojesen, Sune F. Nielsen, Henrik Flyger, Javier Benitez, M. Pilar Zamora, Jose Ignacio Arias Perez, Primitiva Menéndez, Hoda Anton-Culver, Susan L. Neuhausen, Argyrios Ziogas, Christina A. Clarke, Hermann Brenner, Volker Arndt, Christa Stegmaier, Hiltrud Brauch, Thomas Brüning, Yon Dschun Ko, Taru A. Muranen, Kristiina Aittomäki, Carl Blomqvist, Natalia V. Bogdanova, Natalia N. Antonenkova, Annika Lindblom, Sara Margolin, Arto Mannermaa, Vesa Kataja, Veli Matti Kosma, Jaana M. Hartikainen, Amanda B. Spurdle, Els Wauters, Dominiek Smeets, Benoit Beuselinck, Giuseppe Floris, Jenny Chang-Claude, Anja Rudolph, Petra Seibold, Dieter Flesch-Janys, Janet E. Olson, Celine Vachon, Vernon S. Pankratz, Catriona McLean, Christopher A. Haiman, Brian E. Henderson, Fredrick R. Schumacher, Loic Le Marchand, Vessela Kristensen, Grethe Grenaker Alnaes, Wei Zheng, David J. Hunter, Sara Lindström, Susan E. Hankinson, Peter Kraft, Irene L. Andrulis, Julia A. Knight, Gord Glendon, Anna Marie Mulligan, Arja Jukkola-Vuorinen, Mervi Grip, Saila Kauppila, Peter Devilee, Robert A E M Tollenaar, Caroline Seynaeve, Antoinette Hollestelle, Montse Garcia-Closas, Jonine D. Figueroa, Stephen J. Chanock, Jolanta Lissowska, Kamila Czene, Hatef Darabi, Mikael Eriksson, Diana Eccles, Sajjad Rafiq, William J. Tapper, Sue M. Gerty, Maartje J. Hooning, John W M Martens, J. Margriet Collée, M. M A Tilanus-Linthorst, Per Hall, Jingmei Li, Judith S. Brand, Keith Humphreys, Angela Cox, Malcolm W R Reed, Craig Luccarini, Caroline Baynes, Alison Dunning, Ute Hamann, Diana Torres, Hans Ulrich Ulmer, Thomas Rüdiger, Anna Jakubowska, Jan Lubinski, Katarzyna Jaworska, Katarzyna Durda, Susan Slager, Amanda E. Toland, Christine B. Ambrosone, Drakoulis Yannoukakos, Anthony J. Swerdlow, Alan Ashworth, Nick Orr, Michael E. Jones, Anna González-Neira, Guillermo Pita, M. Rosario Alonso, Nuria Álvarez, Daniel Herrero, Daniel C. Tessier, Daniel Vincent, Francois Bacot, Jacques Simard, Martine Dumont, Penny Soucy, Rosalind Eeles, Kenneth Muir, Fredrik Wiklund, Henrik Grönberg, Johanna Schleutker, Børge G. Nordestgaard, Maren Weischer, Ruth C. Travis, David E. Neal, J. L. Donovan, Freddie C. Hamdy, Kay Thee Khaw, J. L. Stanford, William J. Blot, Stephen Thibodeau, D. J. Schaid, Joseph L. Kelley, Christiane Maier, Adam S. Kibel, Cezary Cybulski, Lisa Cannon-Albright, Katja Butterbach, Jong Park, R. Kaneva, Jyotsna Batra, Manuel R. Teixeira, Zsofia Kote-Jarai, Ali Amin Al Olama, Sara Benlloch, S. P. Renner, Arndt Hartmann, Alexander Hein, Matthias Ruebner, Diether Lambrechts, Els Van Nieuwenhuysen, Ignace Vergote, Sandrina Lambretchs, Jennifer A. Doherty, Mary Anne Rossing, Stefan Nickels, Ursula Eilber, Shan Wang-Gohrke, Kunle Odunsi, Lara E. Sucheston-Campbell, Grace Friel, G. Lurie, Jeffrey L. Killeen, Lynne R. Wilkens, Marc T. Goodman, I. B. Runnebaum, Peter Hillemanns, Liisa M. Pelttari, Ralf Butzow, Francesmary Modugno, Robert P. Edwards, R. B. Ness, Kirsten B. Moysich, A. du Bois, Florian Heitz, Philipp Harter, Stefan Kommoss, Beth Y. Karlan, Christine S. Walsh, Jenny Lester, Allan Jensen, Susanne Krüger Kjær, Estrid Hogdall, Bernard Gilles Peissel, Bernardo Bonanni, Loris Bernard, Ellen L. Goode, Brooke L. Fridley, Robert A. Vierkant, Julie Cunningham, Melissa C. Larson, Zachary C. Fogarty, Kimberly R. Kalli, Dong Liang, Karen H. Lu, Michelle A T Hildebrandt, Xifeng Wu, Douglas A. Levine, Fanny Dao, Maria Bisogna, Andrew Berchuck, Edwin S. Iversen, Jeffrey R. Marks, Lucy Akushevich, Daniel W. Cramer, Joellen M. Schildkraut, Kathryn L. Terry, Elizabeth M. Poole, M. Stampfer, Shelley S. Tworoger, Elisa V. Bandera, Irene Orlow, Sara H. Olson, Line Bjorge, Helga B. Salvesen, Anne M. Van Altena, Katja K H Aben, Lambartus Kiemeney, Leon F A G Massuger, Tanja Pejovic, Yukie Bean, Angela Brooks-Wilson, Linda E. Kelemen, Linda S. Cook, Nhu D. Le, Bohdan Gorski, Jacek Gronwald, Janusz Menkiszak, Claus Hogdall, Lene Lundvall, Lotte Nedergaard, Svend Aage Engelholm, Ed Dicks, Jonathan Tyrer, Ian Campbell, Iain A. McNeish, James Paul, Nadeem Siddiqui, Rosalind Glasspool, Alice S. Whittemore, Joseph H. Rothstein, Valerie McGuire, Weiva Sieh, Hui Cai, Xiao Ou Shu, Rachel T. Teten, Rebecca Sutphen, John R. McLaughlin, S. A. Narod, Catherine M. Phelan, Alvaro N. Monteiro, David A. Fenstermacher, Hui Yi Lin, Jennifer B. Permuth, Thomas A. Sellers, Y. Ann Chen, Ya Yu Tsai, Zhihua Chen, Aleksandra Gentry-Maharaj, Simon A. Gayther, Susan J. Ramus, Usha Menon, Anna H. Wu, Celeste L. Pearce, David Van Den Berg, Malcolm C. Pike, Agnieszka Dansonka-Mieszkowska, Joanna Plisiecka-Halasa, Joanna Moes-Sosnowska, Jolanta Kupryjanczyk, Paul D P Pharoah, Honglin Song, Ingrid M. Winship, Georgia Chenevix-Trench, Graham G. Giles, Sean V. Tavtigian, Douglas F. Easton, Roger L. Milne

Research output: Contribution to journalArticle

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=7.1×10-5), 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.

Original languageEnglish
JournalJournal of Medical Genetics
DOIs
Publication statusAccepted/In press - Sep 2 2016

Fingerprint

Neoplasms
Breast Neoplasms
Mutation
Ovarian Neoplasms
Case-Control Studies
Prostate
Prostatic Neoplasms
Population
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Southey, M., Goldgar, D. E., Winqvist, R., Pylkäs, K., Couch, F. J., Tischkowitz, M., ... Milne, R. L. (Accepted/In press). PALB2, CHEK2 and ATM rare variants and cancer risk: Data from COGS. Journal of Medical Genetics. https://doi.org/10.1136/jmedgenet-2016-103839

PALB2, CHEK2 and ATM rare variants and cancer risk : Data from COGS. / Southey, Melissa; Goldgar, David E.; Winqvist, Robert; Pylkäs, Katri; Couch, Fergus J.; Tischkowitz, Marc; Foulkes, W. D.; Dennis, Joe; Michailidou, Kyriaki; van Rensburg, Elizabeth J.; Heikkinen, Tuomas; Nevanlinna, Heli; Hopper, John; Dörk, Thilo; Claes, Kathleen; Reis-Filho, Jorge S.; Teo, Z. L.; Radice, Paolo; Catucci, Irene; Peterlongo, Paolo; Tsimiklis, Helen; Odefrey, Fabrice; Dowty, James G.; Schmidt, Marjanka K.; Broeks, Annegien; Hogervorst, Frans B.; Verhoef, S.; Carpenter, Jane; Clarke, Christine; Scott, Rodney J.; Fasching, Peter A.; Haeberle, Lothar; Ekici, Arif B.; Beckmann, Matthias W.; Peto, Julian; Dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Bolla, Manjeet K.; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Marme, Federik; Burwinkel, Barbara; Yang, Rongxi; Guenel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Bojesen, Stig E.; Nielsen, Sune F.; Flyger, Henrik; Benitez, Javier; Zamora, M. Pilar; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Anton-Culver, Hoda; Neuhausen, Susan L.; Ziogas, Argyrios; Clarke, Christina A.; Brenner, Hermann; Arndt, Volker; Stegmaier, Christa; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon Dschun; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli Matti; Hartikainen, Jaana M.; Spurdle, Amanda B.; Wauters, Els; Smeets, Dominiek; Beuselinck, Benoit; Floris, Giuseppe; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Olson, Janet E.; Vachon, Celine; Pankratz, Vernon S.; McLean, Catriona; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick R.; Marchand, Loic Le; Kristensen, Vessela; Alnaes, Grethe Grenaker; Zheng, Wei; Hunter, David J.; Lindström, Sara; Hankinson, Susan E.; Kraft, Peter; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Jukkola-Vuorinen, Arja; Grip, Mervi; Kauppila, Saila; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Hollestelle, Antoinette; Garcia-Closas, Montse; Figueroa, Jonine D.; Chanock, Stephen J.; Lissowska, Jolanta; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Eccles, Diana; Rafiq, Sajjad; Tapper, William J.; Gerty, Sue M.; Hooning, Maartje J.; Martens, John W M; Collée, J. Margriet; Tilanus-Linthorst, M. M A; Hall, Per; Li, Jingmei; Brand, Judith S.; Humphreys, Keith; Cox, Angela; Reed, Malcolm W R; Luccarini, Craig; Baynes, Caroline; Dunning, Alison; Hamann, Ute; Torres, Diana; Ulmer, Hans Ulrich; Rüdiger, Thomas; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Slager, Susan; Toland, Amanda E.; Ambrosone, Christine B.; Yannoukakos, Drakoulis; Swerdlow, Anthony J.; Ashworth, Alan; Orr, Nick; Jones, Michael E.; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Simard, Jacques; Dumont, Martine; Soucy, Penny; Eeles, Rosalind; Muir, Kenneth; Wiklund, Fredrik; Grönberg, Henrik; Schleutker, Johanna; Nordestgaard, Børge G.; Weischer, Maren; Travis, Ruth C.; Neal, David E.; Donovan, J. L.; Hamdy, Freddie C.; Khaw, Kay Thee; Stanford, J. L.; Blot, William J.; Thibodeau, Stephen; Schaid, D. J.; Kelley, Joseph L.; Maier, Christiane; Kibel, Adam S.; Cybulski, Cezary; Cannon-Albright, Lisa; Butterbach, Katja; Park, Jong; Kaneva, R.; Batra, Jyotsna; Teixeira, Manuel R.; Kote-Jarai, Zsofia; Olama, Ali Amin Al; Benlloch, Sara; Renner, S. P.; Hartmann, Arndt; Hein, Alexander; Ruebner, Matthias; Lambrechts, Diether; Nieuwenhuysen, Els Van; Vergote, Ignace; Lambretchs, Sandrina; Doherty, Jennifer A.; Rossing, Mary Anne; Nickels, Stefan; Eilber, Ursula; Wang-Gohrke, Shan; Odunsi, Kunle; Sucheston-Campbell, Lara E.; Friel, Grace; Lurie, G.; Killeen, Jeffrey L.; Wilkens, Lynne R.; Goodman, Marc T.; Runnebaum, I. B.; Hillemanns, Peter; Pelttari, Liisa M.; Butzow, Ralf; Modugno, Francesmary; Edwards, Robert P.; Ness, R. B.; Moysich, Kirsten B.; du Bois, A.; Heitz, Florian; Harter, Philipp; Kommoss, Stefan; Karlan, Beth Y.; Walsh, Christine S.; Lester, Jenny; Jensen, Allan; Kjær, Susanne Krüger; Hogdall, Estrid; Peissel, Bernard Gilles; Bonanni, Bernardo; Bernard, Loris; Goode, Ellen L.; Fridley, Brooke L.; Vierkant, Robert A.; Cunningham, Julie; Larson, Melissa C.; Fogarty, Zachary C.; Kalli, Kimberly R.; Liang, Dong; Lu, Karen H.; Hildebrandt, Michelle A T; Wu, Xifeng; Levine, Douglas A.; Dao, Fanny; Bisogna, Maria; Berchuck, Andrew; Iversen, Edwin S.; Marks, Jeffrey R.; Akushevich, Lucy; Cramer, Daniel W.; Schildkraut, Joellen M.; Terry, Kathryn L.; Poole, Elizabeth M.; Stampfer, M.; Tworoger, Shelley S.; Bandera, Elisa V.; Orlow, Irene; Olson, Sara H.; Bjorge, Line; Salvesen, Helga B.; Van Altena, Anne M.; Aben, Katja K H; Kiemeney, Lambartus; Massuger, Leon F A G; Pejovic, Tanja; Bean, Yukie; Brooks-Wilson, Angela; Kelemen, Linda E.; Cook, Linda S.; Le, Nhu D.; Gorski, Bohdan; Gronwald, Jacek; Menkiszak, Janusz; Hogdall, Claus; Lundvall, Lene; Nedergaard, Lotte; Engelholm, Svend Aage; Dicks, Ed; Tyrer, Jonathan; Campbell, Ian; McNeish, Iain A.; Paul, James; Siddiqui, Nadeem; Glasspool, Rosalind; Whittemore, Alice S.; Rothstein, Joseph H.; McGuire, Valerie; Sieh, Weiva; Cai, Hui; Shu, Xiao Ou; Teten, Rachel T.; Sutphen, Rebecca; McLaughlin, John R.; Narod, S. A.; Phelan, Catherine M.; Monteiro, Alvaro N.; Fenstermacher, David A.; Lin, Hui Yi; Permuth, Jennifer B.; Sellers, Thomas A.; Chen, Y. Ann; Tsai, Ya Yu; Chen, Zhihua; Gentry-Maharaj, Aleksandra; Gayther, Simon A.; Ramus, Susan J.; Menon, Usha; Wu, Anna H.; Pearce, Celeste L.; Van Den Berg, David; Pike, Malcolm C.; Dansonka-Mieszkowska, Agnieszka; Plisiecka-Halasa, Joanna; Moes-Sosnowska, Joanna; Kupryjanczyk, Jolanta; Pharoah, Paul D P; Song, Honglin; Winship, Ingrid M.; Chenevix-Trench, Georgia; Giles, Graham G.; Tavtigian, Sean V.; Easton, Douglas F.; Milne, Roger L.

In: Journal of Medical Genetics, 02.09.2016.

Research output: Contribution to journalArticle

Southey, M, Goldgar, DE, Winqvist, R, Pylkäs, K, Couch, FJ, Tischkowitz, M, Foulkes, WD, Dennis, J, Michailidou, K, van Rensburg, EJ, Heikkinen, T, Nevanlinna, H, Hopper, J, Dörk, T, Claes, K, Reis-Filho, JS, Teo, ZL, Radice, P, Catucci, I, Peterlongo, P, Tsimiklis, H, Odefrey, F, Dowty, JG, Schmidt, MK, Broeks, A, Hogervorst, FB, Verhoef, S, Carpenter, J, Clarke, C, Scott, RJ, Fasching, PA, Haeberle, L, Ekici, AB, Beckmann, MW, Peto, J, Dos-Santos-Silva, I, Fletcher, O, Johnson, N, Bolla, MK, Sawyer, EJ, Tomlinson, I, Kerin, MJ, Miller, N, Marme, F, Burwinkel, B, Yang, R, Guenel, P, Truong, T, Menegaux, F, Sanchez, M, Bojesen, SE, Nielsen, SF, Flyger, H, Benitez, J, Zamora, MP, Perez, JIA, Menéndez, P, Anton-Culver, H, Neuhausen, SL, Ziogas, A, Clarke, CA, Brenner, H, Arndt, V, Stegmaier, C, Brauch, H, Brüning, T, Ko, YD, Muranen, TA, Aittomäki, K, Blomqvist, C, Bogdanova, NV, Antonenkova, NN, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, VM, Hartikainen, JM, Spurdle, AB, Wauters, E, Smeets, D, Beuselinck, B, Floris, G, Chang-Claude, J, Rudolph, A, Seibold, P, Flesch-Janys, D, Olson, JE, Vachon, C, Pankratz, VS, McLean, C, Haiman, CA, Henderson, BE, Schumacher, FR, Marchand, LL, Kristensen, V, Alnaes, GG, Zheng, W, Hunter, DJ, Lindström, S, Hankinson, SE, Kraft, P, Andrulis, IL, Knight, JA, Glendon, G, Mulligan, AM, Jukkola-Vuorinen, A, Grip, M, Kauppila, S, Devilee, P, Tollenaar, RAEM, Seynaeve, C, Hollestelle, A, Garcia-Closas, M, Figueroa, JD, Chanock, SJ, Lissowska, J, Czene, K, Darabi, H, Eriksson, M, Eccles, D, Rafiq, S, Tapper, WJ, Gerty, SM, Hooning, MJ, Martens, JWM, Collée, JM, Tilanus-Linthorst, MMA, Hall, P, Li, J, Brand, JS, Humphreys, K, Cox, A, Reed, MWR, Luccarini, C, Baynes, C, Dunning, A, Hamann, U, Torres, D, Ulmer, HU, Rüdiger, T, Jakubowska, A, Lubinski, J, Jaworska, K, Durda, K, Slager, S, Toland, AE, Ambrosone, CB, Yannoukakos, D, Swerdlow, AJ, Ashworth, A, Orr, N, Jones, ME, González-Neira, A, Pita, G, Alonso, MR, Álvarez, N, Herrero, D, Tessier, DC, Vincent, D, Bacot, F, Simard, J, Dumont, M, Soucy, P, Eeles, R, Muir, K, Wiklund, F, Grönberg, H, Schleutker, J, Nordestgaard, BG, Weischer, M, Travis, RC, Neal, DE, Donovan, JL, Hamdy, FC, Khaw, KT, Stanford, JL, Blot, WJ, Thibodeau, S, Schaid, DJ, Kelley, JL, Maier, C, Kibel, AS, Cybulski, C, Cannon-Albright, L, Butterbach, K, Park, J, Kaneva, R, Batra, J, Teixeira, MR, Kote-Jarai, Z, Olama, AAA, Benlloch, S, Renner, SP, Hartmann, A, Hein, A, Ruebner, M, Lambrechts, D, Nieuwenhuysen, EV, Vergote, I, Lambretchs, S, Doherty, JA, Rossing, MA, Nickels, S, Eilber, U, Wang-Gohrke, S, Odunsi, K, Sucheston-Campbell, LE, Friel, G, Lurie, G, Killeen, JL, Wilkens, LR, Goodman, MT, Runnebaum, IB, Hillemanns, P, Pelttari, LM, Butzow, R, Modugno, F, Edwards, RP, Ness, RB, Moysich, KB, du Bois, A, Heitz, F, Harter, P, Kommoss, S, Karlan, BY, Walsh, CS, Lester, J, Jensen, A, Kjær, SK, Hogdall, E, Peissel, BG, Bonanni, B, Bernard, L, Goode, EL, Fridley, BL, Vierkant, RA, Cunningham, J, Larson, MC, Fogarty, ZC, Kalli, KR, Liang, D, Lu, KH, Hildebrandt, MAT, Wu, X, Levine, DA, Dao, F, Bisogna, M, Berchuck, A, Iversen, ES, Marks, JR, Akushevich, L, Cramer, DW, Schildkraut, JM, Terry, KL, Poole, EM, Stampfer, M, Tworoger, SS, Bandera, EV, Orlow, I, Olson, SH, Bjorge, L, Salvesen, HB, Van Altena, AM, Aben, KKH, Kiemeney, L, Massuger, LFAG, Pejovic, T, Bean, Y, Brooks-Wilson, A, Kelemen, LE, Cook, LS, Le, ND, Gorski, B, Gronwald, J, Menkiszak, J, Hogdall, C, Lundvall, L, Nedergaard, L, Engelholm, SA, Dicks, E, Tyrer, J, Campbell, I, McNeish, IA, Paul, J, Siddiqui, N, Glasspool, R, Whittemore, AS, Rothstein, JH, McGuire, V, Sieh, W, Cai, H, Shu, XO, Teten, RT, Sutphen, R, McLaughlin, JR, Narod, SA, Phelan, CM, Monteiro, AN, Fenstermacher, DA, Lin, HY, Permuth, JB, Sellers, TA, Chen, YA, Tsai, YY, Chen, Z, Gentry-Maharaj, A, Gayther, SA, Ramus, SJ, Menon, U, Wu, AH, Pearce, CL, Van Den Berg, D, Pike, MC, Dansonka-Mieszkowska, A, Plisiecka-Halasa, J, Moes-Sosnowska, J, Kupryjanczyk, J, Pharoah, PDP, Song, H, Winship, IM, Chenevix-Trench, G, Giles, GG, Tavtigian, SV, Easton, DF & Milne, RL 2016, 'PALB2, CHEK2 and ATM rare variants and cancer risk: Data from COGS', Journal of Medical Genetics. https://doi.org/10.1136/jmedgenet-2016-103839
Southey M, Goldgar DE, Winqvist R, Pylkäs K, Couch FJ, Tischkowitz M et al. PALB2, CHEK2 and ATM rare variants and cancer risk: Data from COGS. Journal of Medical Genetics. 2016 Sep 2. https://doi.org/10.1136/jmedgenet-2016-103839
Southey, Melissa ; Goldgar, David E. ; Winqvist, Robert ; Pylkäs, Katri ; Couch, Fergus J. ; Tischkowitz, Marc ; Foulkes, W. D. ; Dennis, Joe ; Michailidou, Kyriaki ; van Rensburg, Elizabeth J. ; Heikkinen, Tuomas ; Nevanlinna, Heli ; Hopper, John ; Dörk, Thilo ; Claes, Kathleen ; Reis-Filho, Jorge S. ; Teo, Z. L. ; Radice, Paolo ; Catucci, Irene ; Peterlongo, Paolo ; Tsimiklis, Helen ; Odefrey, Fabrice ; Dowty, James G. ; Schmidt, Marjanka K. ; Broeks, Annegien ; Hogervorst, Frans B. ; Verhoef, S. ; Carpenter, Jane ; Clarke, Christine ; Scott, Rodney J. ; Fasching, Peter A. ; Haeberle, Lothar ; Ekici, Arif B. ; Beckmann, Matthias W. ; Peto, Julian ; Dos-Santos-Silva, Isabel ; Fletcher, Olivia ; Johnson, Nichola ; Bolla, Manjeet K. ; Sawyer, Elinor J. ; Tomlinson, Ian ; Kerin, Michael J. ; Miller, Nicola ; Marme, Federik ; Burwinkel, Barbara ; Yang, Rongxi ; Guenel, Pascal ; Truong, Thérèse ; Menegaux, Florence ; Sanchez, Marie ; Bojesen, Stig E. ; Nielsen, Sune F. ; Flyger, Henrik ; Benitez, Javier ; Zamora, M. Pilar ; Perez, Jose Ignacio Arias ; Menéndez, Primitiva ; Anton-Culver, Hoda ; Neuhausen, Susan L. ; Ziogas, Argyrios ; Clarke, Christina A. ; Brenner, Hermann ; Arndt, Volker ; Stegmaier, Christa ; Brauch, Hiltrud ; Brüning, Thomas ; Ko, Yon Dschun ; Muranen, Taru A. ; Aittomäki, Kristiina ; Blomqvist, Carl ; Bogdanova, Natalia V. ; Antonenkova, Natalia N. ; Lindblom, Annika ; Margolin, Sara ; Mannermaa, Arto ; Kataja, Vesa ; Kosma, Veli Matti ; Hartikainen, Jaana M. ; Spurdle, Amanda B. ; Wauters, Els ; Smeets, Dominiek ; Beuselinck, Benoit ; Floris, Giuseppe ; Chang-Claude, Jenny ; Rudolph, Anja ; Seibold, Petra ; Flesch-Janys, Dieter ; Olson, Janet E. ; Vachon, Celine ; Pankratz, Vernon S. ; McLean, Catriona ; Haiman, Christopher A. ; Henderson, Brian E. ; Schumacher, Fredrick R. ; Marchand, Loic Le ; Kristensen, Vessela ; Alnaes, Grethe Grenaker ; Zheng, Wei ; Hunter, David J. ; Lindström, Sara ; Hankinson, Susan E. ; Kraft, Peter ; Andrulis, Irene L. ; Knight, Julia A. ; Glendon, Gord ; Mulligan, Anna Marie ; Jukkola-Vuorinen, Arja ; Grip, Mervi ; Kauppila, Saila ; Devilee, Peter ; Tollenaar, Robert A E M ; Seynaeve, Caroline ; Hollestelle, Antoinette ; Garcia-Closas, Montse ; Figueroa, Jonine D. ; Chanock, Stephen J. ; Lissowska, Jolanta ; Czene, Kamila ; Darabi, Hatef ; Eriksson, Mikael ; Eccles, Diana ; Rafiq, Sajjad ; Tapper, William J. ; Gerty, Sue M. ; Hooning, Maartje J. ; Martens, John W M ; Collée, J. Margriet ; Tilanus-Linthorst, M. M A ; Hall, Per ; Li, Jingmei ; Brand, Judith S. ; Humphreys, Keith ; Cox, Angela ; Reed, Malcolm W R ; Luccarini, Craig ; Baynes, Caroline ; Dunning, Alison ; Hamann, Ute ; Torres, Diana ; Ulmer, Hans Ulrich ; Rüdiger, Thomas ; Jakubowska, Anna ; Lubinski, Jan ; Jaworska, Katarzyna ; Durda, Katarzyna ; Slager, Susan ; Toland, Amanda E. ; Ambrosone, Christine B. ; Yannoukakos, Drakoulis ; Swerdlow, Anthony J. ; Ashworth, Alan ; Orr, Nick ; Jones, Michael E. ; González-Neira, Anna ; Pita, Guillermo ; Alonso, M. Rosario ; Álvarez, Nuria ; Herrero, Daniel ; Tessier, Daniel C. ; Vincent, Daniel ; Bacot, Francois ; Simard, Jacques ; Dumont, Martine ; Soucy, Penny ; Eeles, Rosalind ; Muir, Kenneth ; Wiklund, Fredrik ; Grönberg, Henrik ; Schleutker, Johanna ; Nordestgaard, Børge G. ; Weischer, Maren ; Travis, Ruth C. ; Neal, David E. ; Donovan, J. L. ; Hamdy, Freddie C. ; Khaw, Kay Thee ; Stanford, J. L. ; Blot, William J. ; Thibodeau, Stephen ; Schaid, D. J. ; Kelley, Joseph L. ; Maier, Christiane ; Kibel, Adam S. ; Cybulski, Cezary ; Cannon-Albright, Lisa ; Butterbach, Katja ; Park, Jong ; Kaneva, R. ; Batra, Jyotsna ; Teixeira, Manuel R. ; Kote-Jarai, Zsofia ; Olama, Ali Amin Al ; Benlloch, Sara ; Renner, S. P. ; Hartmann, Arndt ; Hein, Alexander ; Ruebner, Matthias ; Lambrechts, Diether ; Nieuwenhuysen, Els Van ; Vergote, Ignace ; Lambretchs, Sandrina ; Doherty, Jennifer A. ; Rossing, Mary Anne ; Nickels, Stefan ; Eilber, Ursula ; Wang-Gohrke, Shan ; Odunsi, Kunle ; Sucheston-Campbell, Lara E. ; Friel, Grace ; Lurie, G. ; Killeen, Jeffrey L. ; Wilkens, Lynne R. ; Goodman, Marc T. ; Runnebaum, I. B. ; Hillemanns, Peter ; Pelttari, Liisa M. ; Butzow, Ralf ; Modugno, Francesmary ; Edwards, Robert P. ; Ness, R. B. ; Moysich, Kirsten B. ; du Bois, A. ; Heitz, Florian ; Harter, Philipp ; Kommoss, Stefan ; Karlan, Beth Y. ; Walsh, Christine S. ; Lester, Jenny ; Jensen, Allan ; Kjær, Susanne Krüger ; Hogdall, Estrid ; Peissel, Bernard Gilles ; Bonanni, Bernardo ; Bernard, Loris ; Goode, Ellen L. ; Fridley, Brooke L. ; Vierkant, Robert A. ; Cunningham, Julie ; Larson, Melissa C. ; Fogarty, Zachary C. ; Kalli, Kimberly R. ; Liang, Dong ; Lu, Karen H. ; Hildebrandt, Michelle A T ; Wu, Xifeng ; Levine, Douglas A. ; Dao, Fanny ; Bisogna, Maria ; Berchuck, Andrew ; Iversen, Edwin S. ; Marks, Jeffrey R. ; Akushevich, Lucy ; Cramer, Daniel W. ; Schildkraut, Joellen M. ; Terry, Kathryn L. ; Poole, Elizabeth M. ; Stampfer, M. ; Tworoger, Shelley S. ; Bandera, Elisa V. ; Orlow, Irene ; Olson, Sara H. ; Bjorge, Line ; Salvesen, Helga B. ; Van Altena, Anne M. ; Aben, Katja K H ; Kiemeney, Lambartus ; Massuger, Leon F A G ; Pejovic, Tanja ; Bean, Yukie ; Brooks-Wilson, Angela ; Kelemen, Linda E. ; Cook, Linda S. ; Le, Nhu D. ; Gorski, Bohdan ; Gronwald, Jacek ; Menkiszak, Janusz ; Hogdall, Claus ; Lundvall, Lene ; Nedergaard, Lotte ; Engelholm, Svend Aage ; Dicks, Ed ; Tyrer, Jonathan ; Campbell, Ian ; McNeish, Iain A. ; Paul, James ; Siddiqui, Nadeem ; Glasspool, Rosalind ; Whittemore, Alice S. ; Rothstein, Joseph H. ; McGuire, Valerie ; Sieh, Weiva ; Cai, Hui ; Shu, Xiao Ou ; Teten, Rachel T. ; Sutphen, Rebecca ; McLaughlin, John R. ; Narod, S. A. ; Phelan, Catherine M. ; Monteiro, Alvaro N. ; Fenstermacher, David A. ; Lin, Hui Yi ; Permuth, Jennifer B. ; Sellers, Thomas A. ; Chen, Y. Ann ; Tsai, Ya Yu ; Chen, Zhihua ; Gentry-Maharaj, Aleksandra ; Gayther, Simon A. ; Ramus, Susan J. ; Menon, Usha ; Wu, Anna H. ; Pearce, Celeste L. ; Van Den Berg, David ; Pike, Malcolm C. ; Dansonka-Mieszkowska, Agnieszka ; Plisiecka-Halasa, Joanna ; Moes-Sosnowska, Joanna ; Kupryjanczyk, Jolanta ; Pharoah, Paul D P ; Song, Honglin ; Winship, Ingrid M. ; Chenevix-Trench, Georgia ; Giles, Graham G. ; Tavtigian, Sean V. ; Easton, Douglas F. ; Milne, Roger L. / PALB2, CHEK2 and ATM rare variants and cancer risk : Data from COGS. In: Journal of Medical Genetics. 2016.
@article{ae974530521d476bb78bf3567ae22084,
title = "PALB2, CHEK2 and ATM rare variants and cancer risk: Data from COGS",
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=7.1×10-5), 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.",
author = "Melissa Southey and Goldgar, {David E.} and Robert Winqvist and Katri Pylk{\"a}s and Couch, {Fergus J.} and Marc Tischkowitz and Foulkes, {W. D.} and Joe Dennis and Kyriaki Michailidou and {van Rensburg}, {Elizabeth J.} and Tuomas Heikkinen and Heli Nevanlinna and John Hopper and Thilo D{\"o}rk and Kathleen Claes and Reis-Filho, {Jorge S.} and Teo, {Z. L.} and Paolo Radice and Irene Catucci and Paolo Peterlongo and Helen Tsimiklis and Fabrice Odefrey and Dowty, {James G.} and Schmidt, {Marjanka K.} and Annegien Broeks and Hogervorst, {Frans B.} and S. Verhoef and Jane Carpenter and Christine Clarke and Scott, {Rodney J.} and Fasching, {Peter A.} and Lothar Haeberle and Ekici, {Arif B.} and Beckmann, {Matthias W.} and Julian Peto and Isabel Dos-Santos-Silva and Olivia Fletcher and Nichola Johnson and Bolla, {Manjeet K.} and Sawyer, {Elinor J.} and Ian Tomlinson and Kerin, {Michael J.} and Nicola Miller and Federik Marme and Barbara Burwinkel and Rongxi Yang and Pascal Guenel and Th{\'e}r{\`e}se Truong and Florence Menegaux and Marie Sanchez and Bojesen, {Stig E.} and Nielsen, {Sune F.} and Henrik Flyger and Javier Benitez and Zamora, {M. Pilar} and Perez, {Jose Ignacio Arias} and Primitiva Men{\'e}ndez and Hoda Anton-Culver and Neuhausen, {Susan L.} and Argyrios Ziogas and Clarke, {Christina A.} and Hermann Brenner and Volker Arndt and Christa Stegmaier and Hiltrud Brauch and Thomas Br{\"u}ning and Ko, {Yon Dschun} and Muranen, {Taru A.} and Kristiina Aittom{\"a}ki and Carl Blomqvist and Bogdanova, {Natalia V.} and Antonenkova, {Natalia N.} and Annika Lindblom and Sara Margolin and Arto Mannermaa and Vesa Kataja and Kosma, {Veli Matti} and Hartikainen, {Jaana M.} and Spurdle, {Amanda B.} 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 Olson, {Janet E.} and Celine Vachon and Pankratz, {Vernon S.} and Catriona McLean and Haiman, {Christopher A.} and Henderson, {Brian E.} and Schumacher, {Fredrick R.} and Marchand, {Loic Le} and Vessela Kristensen and Alnaes, {Grethe Grenaker} and Wei Zheng and Hunter, {David J.} and Sara Lindstr{\"o}m and Hankinson, {Susan E.} and Peter Kraft and Andrulis, {Irene L.} and Knight, {Julia A.} and Gord Glendon and Mulligan, {Anna Marie} and Arja Jukkola-Vuorinen and Mervi Grip and Saila Kauppila and Peter Devilee and Tollenaar, {Robert A E M} and Caroline Seynaeve and Antoinette Hollestelle and Montse Garcia-Closas and Figueroa, {Jonine D.} and Chanock, {Stephen J.} and Jolanta Lissowska and Kamila Czene and Hatef Darabi and Mikael Eriksson and Diana Eccles and Sajjad Rafiq and Tapper, {William J.} and Gerty, {Sue M.} and Hooning, {Maartje J.} and Martens, {John W M} and Coll{\'e}e, {J. Margriet} and Tilanus-Linthorst, {M. M A} and Per Hall and Jingmei Li and Brand, {Judith S.} and Keith Humphreys and Angela Cox and Reed, {Malcolm W R} and Craig Luccarini and Caroline Baynes and Alison Dunning and Ute Hamann and Diana Torres and Ulmer, {Hans Ulrich} and Thomas R{\"u}diger and Anna Jakubowska and Jan Lubinski and Katarzyna Jaworska and Katarzyna Durda and Susan Slager and Toland, {Amanda E.} and Ambrosone, {Christine B.} and Drakoulis Yannoukakos and Swerdlow, {Anthony J.} and Alan Ashworth and Nick Orr and Jones, {Michael E.} and Anna Gonz{\'a}lez-Neira and Guillermo Pita and Alonso, {M. Rosario} and Nuria {\'A}lvarez and Daniel Herrero and Tessier, {Daniel C.} 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 Gr{\"o}nberg and Johanna Schleutker and Nordestgaard, {B{\o}rge G.} and Maren Weischer and Travis, {Ruth C.} and Neal, {David E.} and Donovan, {J. L.} and Hamdy, {Freddie C.} and Khaw, {Kay Thee} and Stanford, {J. L.} and Blot, {William J.} and Stephen Thibodeau and Schaid, {D. J.} and Kelley, {Joseph L.} and Christiane Maier and Kibel, {Adam S.} and Cezary Cybulski and Lisa Cannon-Albright and Katja Butterbach and Jong Park and R. Kaneva and Jyotsna Batra and Teixeira, {Manuel R.} and Zsofia Kote-Jarai and Olama, {Ali Amin Al} and Sara Benlloch and Renner, {S. P.} and Arndt Hartmann and Alexander Hein and Matthias Ruebner and Diether Lambrechts and Nieuwenhuysen, {Els Van} and Ignace Vergote and Sandrina Lambretchs and Doherty, {Jennifer A.} and Rossing, {Mary Anne} and Stefan Nickels and Ursula Eilber and Shan Wang-Gohrke and Kunle Odunsi and Sucheston-Campbell, {Lara E.} and Grace Friel and G. Lurie and Killeen, {Jeffrey L.} and Wilkens, {Lynne R.} and Goodman, {Marc T.} and Runnebaum, {I. B.} and Peter Hillemanns and Pelttari, {Liisa M.} and Ralf Butzow and Francesmary Modugno and Edwards, {Robert P.} and Ness, {R. B.} and Moysich, {Kirsten B.} and {du Bois}, A. and Florian Heitz and Philipp Harter and Stefan Kommoss and Karlan, {Beth Y.} and Walsh, {Christine S.} and Jenny Lester and Allan Jensen and Kj{\ae}r, {Susanne Kr{\"u}ger} and Estrid Hogdall and Peissel, {Bernard Gilles} and Bernardo Bonanni and Loris Bernard and Goode, {Ellen L.} and Fridley, {Brooke L.} and Vierkant, {Robert A.} and Julie Cunningham and Larson, {Melissa C.} and Fogarty, {Zachary C.} and Kalli, {Kimberly R.} and Dong Liang and Lu, {Karen H.} and Hildebrandt, {Michelle A T} and Xifeng Wu and Levine, {Douglas A.} and Fanny Dao and Maria Bisogna and Andrew Berchuck and Iversen, {Edwin S.} and Marks, {Jeffrey R.} and Lucy Akushevich and Cramer, {Daniel W.} and Schildkraut, {Joellen M.} and Terry, {Kathryn L.} and Poole, {Elizabeth M.} and M. Stampfer and Tworoger, {Shelley S.} and Bandera, {Elisa V.} and Irene Orlow and Olson, {Sara H.} and Line Bjorge and Salvesen, {Helga B.} and {Van Altena}, {Anne M.} and Aben, {Katja K H} and Lambartus Kiemeney and Massuger, {Leon F A G} and Tanja Pejovic and Yukie Bean and Angela Brooks-Wilson and Kelemen, {Linda E.} and Cook, {Linda S.} and Le, {Nhu D.} and Bohdan Gorski and Jacek Gronwald and Janusz Menkiszak and Claus Hogdall and Lene Lundvall and Lotte Nedergaard and Engelholm, {Svend Aage} and Ed Dicks and Jonathan Tyrer and Ian Campbell and McNeish, {Iain A.} and James Paul and Nadeem Siddiqui and Rosalind Glasspool and Whittemore, {Alice S.} and Rothstein, {Joseph H.} and Valerie McGuire and Weiva Sieh and Hui Cai and Shu, {Xiao Ou} and Teten, {Rachel T.} and Rebecca Sutphen and McLaughlin, {John R.} and Narod, {S. A.} and Phelan, {Catherine M.} and Monteiro, {Alvaro N.} and Fenstermacher, {David A.} and Lin, {Hui Yi} and Permuth, {Jennifer B.} and Sellers, {Thomas A.} and Chen, {Y. Ann} and Tsai, {Ya Yu} and Zhihua Chen and Aleksandra Gentry-Maharaj and Gayther, {Simon A.} and Ramus, {Susan J.} and Usha Menon and Wu, {Anna H.} and Pearce, {Celeste L.} and {Van Den Berg}, David and Pike, {Malcolm C.} and Agnieszka Dansonka-Mieszkowska and Joanna Plisiecka-Halasa and Joanna Moes-Sosnowska and Jolanta Kupryjanczyk and Pharoah, {Paul D P} and Honglin Song and Winship, {Ingrid M.} and Georgia Chenevix-Trench and Giles, {Graham G.} and Tavtigian, {Sean V.} and Easton, {Douglas F.} and Milne, {Roger L.}",
year = "2016",
month = "9",
day = "2",
doi = "10.1136/jmedgenet-2016-103839",
language = "English",
journal = "Journal of Medical Genetics",
issn = "0022-2593",
publisher = "BMJ Publishing Group",

}

TY - JOUR

T1 - PALB2, CHEK2 and ATM rare variants and cancer risk

T2 - Data from COGS

AU - Southey, Melissa

AU - Goldgar, David E.

AU - Winqvist, Robert

AU - Pylkäs, Katri

AU - Couch, Fergus J.

AU - Tischkowitz, Marc

AU - Foulkes, W. D.

AU - Dennis, Joe

AU - Michailidou, Kyriaki

AU - van Rensburg, Elizabeth J.

AU - Heikkinen, Tuomas

AU - Nevanlinna, Heli

AU - Hopper, John

AU - Dörk, Thilo

AU - Claes, Kathleen

AU - Reis-Filho, Jorge S.

AU - Teo, Z. L.

AU - Radice, Paolo

AU - Catucci, Irene

AU - Peterlongo, Paolo

AU - Tsimiklis, Helen

AU - Odefrey, Fabrice

AU - Dowty, James G.

AU - Schmidt, Marjanka K.

AU - Broeks, Annegien

AU - Hogervorst, Frans B.

AU - Verhoef, S.

AU - Carpenter, Jane

AU - Clarke, Christine

AU - Scott, Rodney J.

AU - Fasching, Peter A.

AU - Haeberle, Lothar

AU - Ekici, Arif B.

AU - Beckmann, Matthias W.

AU - Peto, Julian

AU - Dos-Santos-Silva, Isabel

AU - Fletcher, Olivia

AU - Johnson, Nichola

AU - Bolla, Manjeet K.

AU - Sawyer, Elinor J.

AU - Tomlinson, Ian

AU - Kerin, Michael J.

AU - Miller, Nicola

AU - Marme, Federik

AU - Burwinkel, Barbara

AU - Yang, Rongxi

AU - Guenel, Pascal

AU - Truong, Thérèse

AU - Menegaux, Florence

AU - Sanchez, Marie

AU - Bojesen, Stig E.

AU - Nielsen, Sune F.

AU - Flyger, Henrik

AU - Benitez, Javier

AU - Zamora, M. Pilar

AU - Perez, Jose Ignacio Arias

AU - Menéndez, Primitiva

AU - Anton-Culver, Hoda

AU - Neuhausen, Susan L.

AU - Ziogas, Argyrios

AU - Clarke, Christina A.

AU - Brenner, Hermann

AU - Arndt, Volker

AU - Stegmaier, Christa

AU - Brauch, Hiltrud

AU - Brüning, Thomas

AU - Ko, Yon Dschun

AU - Muranen, Taru A.

AU - Aittomäki, Kristiina

AU - Blomqvist, Carl

AU - Bogdanova, Natalia V.

AU - Antonenkova, Natalia N.

AU - Lindblom, Annika

AU - Margolin, Sara

AU - Mannermaa, Arto

AU - Kataja, Vesa

AU - Kosma, Veli Matti

AU - Hartikainen, Jaana M.

AU - Spurdle, Amanda B.

AU - Wauters, Els

AU - Smeets, Dominiek

AU - Beuselinck, Benoit

AU - Floris, Giuseppe

AU - Chang-Claude, Jenny

AU - Rudolph, Anja

AU - Seibold, Petra

AU - Flesch-Janys, Dieter

AU - Olson, Janet E.

AU - Vachon, Celine

AU - Pankratz, Vernon S.

AU - McLean, Catriona

AU - Haiman, Christopher A.

AU - Henderson, Brian E.

AU - Schumacher, Fredrick R.

AU - Marchand, Loic Le

AU - Kristensen, Vessela

AU - Alnaes, Grethe Grenaker

AU - Zheng, Wei

AU - Hunter, David J.

AU - Lindström, Sara

AU - Hankinson, Susan E.

AU - Kraft, Peter

AU - Andrulis, Irene L.

AU - Knight, Julia A.

AU - Glendon, Gord

AU - Mulligan, Anna Marie

AU - Jukkola-Vuorinen, Arja

AU - Grip, Mervi

AU - Kauppila, Saila

AU - Devilee, Peter

AU - Tollenaar, Robert A E M

AU - Seynaeve, Caroline

AU - Hollestelle, Antoinette

AU - Garcia-Closas, Montse

AU - Figueroa, Jonine D.

AU - Chanock, Stephen J.

AU - Lissowska, Jolanta

AU - Czene, Kamila

AU - Darabi, Hatef

AU - Eriksson, Mikael

AU - Eccles, Diana

AU - Rafiq, Sajjad

AU - Tapper, William J.

AU - Gerty, Sue M.

AU - Hooning, Maartje J.

AU - Martens, John W M

AU - Collée, J. Margriet

AU - Tilanus-Linthorst, M. M A

AU - Hall, Per

AU - Li, Jingmei

AU - Brand, Judith S.

AU - Humphreys, Keith

AU - Cox, Angela

AU - Reed, Malcolm W R

AU - Luccarini, Craig

AU - Baynes, Caroline

AU - Dunning, Alison

AU - Hamann, Ute

AU - Torres, Diana

AU - Ulmer, Hans Ulrich

AU - Rüdiger, Thomas

AU - Jakubowska, Anna

AU - Lubinski, Jan

AU - Jaworska, Katarzyna

AU - Durda, Katarzyna

AU - Slager, Susan

AU - Toland, Amanda E.

AU - Ambrosone, Christine B.

AU - Yannoukakos, Drakoulis

AU - Swerdlow, Anthony J.

AU - Ashworth, Alan

AU - Orr, Nick

AU - Jones, Michael E.

AU - González-Neira, Anna

AU - Pita, Guillermo

AU - Alonso, M. Rosario

AU - Álvarez, Nuria

AU - Herrero, Daniel

AU - Tessier, Daniel C.

AU - Vincent, Daniel

AU - Bacot, Francois

AU - Simard, Jacques

AU - Dumont, Martine

AU - Soucy, Penny

AU - Eeles, Rosalind

AU - Muir, Kenneth

AU - Wiklund, Fredrik

AU - Grönberg, Henrik

AU - Schleutker, Johanna

AU - Nordestgaard, Børge G.

AU - Weischer, Maren

AU - Travis, Ruth C.

AU - Neal, David E.

AU - Donovan, J. L.

AU - Hamdy, Freddie C.

AU - Khaw, Kay Thee

AU - Stanford, J. L.

AU - Blot, William J.

AU - Thibodeau, Stephen

AU - Schaid, D. J.

AU - Kelley, Joseph L.

AU - Maier, Christiane

AU - Kibel, Adam S.

AU - Cybulski, Cezary

AU - Cannon-Albright, Lisa

AU - Butterbach, Katja

AU - Park, Jong

AU - Kaneva, R.

AU - Batra, Jyotsna

AU - Teixeira, Manuel R.

AU - Kote-Jarai, Zsofia

AU - Olama, Ali Amin Al

AU - Benlloch, Sara

AU - Renner, S. P.

AU - Hartmann, Arndt

AU - Hein, Alexander

AU - Ruebner, Matthias

AU - Lambrechts, Diether

AU - Nieuwenhuysen, Els Van

AU - Vergote, Ignace

AU - Lambretchs, Sandrina

AU - Doherty, Jennifer A.

AU - Rossing, Mary Anne

AU - Nickels, Stefan

AU - Eilber, Ursula

AU - Wang-Gohrke, Shan

AU - Odunsi, Kunle

AU - Sucheston-Campbell, Lara E.

AU - Friel, Grace

AU - Lurie, G.

AU - Killeen, Jeffrey L.

AU - Wilkens, Lynne R.

AU - Goodman, Marc T.

AU - Runnebaum, I. B.

AU - Hillemanns, Peter

AU - Pelttari, Liisa M.

AU - Butzow, Ralf

AU - Modugno, Francesmary

AU - Edwards, Robert P.

AU - Ness, R. B.

AU - Moysich, Kirsten B.

AU - du Bois, A.

AU - Heitz, Florian

AU - Harter, Philipp

AU - Kommoss, Stefan

AU - Karlan, Beth Y.

AU - Walsh, Christine S.

AU - Lester, Jenny

AU - Jensen, Allan

AU - Kjær, Susanne Krüger

AU - Hogdall, Estrid

AU - Peissel, Bernard Gilles

AU - Bonanni, Bernardo

AU - Bernard, Loris

AU - Goode, Ellen L.

AU - Fridley, Brooke L.

AU - Vierkant, Robert A.

AU - Cunningham, Julie

AU - Larson, Melissa C.

AU - Fogarty, Zachary C.

AU - Kalli, Kimberly R.

AU - Liang, Dong

AU - Lu, Karen H.

AU - Hildebrandt, Michelle A T

AU - Wu, Xifeng

AU - Levine, Douglas A.

AU - Dao, Fanny

AU - Bisogna, Maria

AU - Berchuck, Andrew

AU - Iversen, Edwin S.

AU - Marks, Jeffrey R.

AU - Akushevich, Lucy

AU - Cramer, Daniel W.

AU - Schildkraut, Joellen M.

AU - Terry, Kathryn L.

AU - Poole, Elizabeth M.

AU - Stampfer, M.

AU - Tworoger, Shelley S.

AU - Bandera, Elisa V.

AU - Orlow, Irene

AU - Olson, Sara H.

AU - Bjorge, Line

AU - Salvesen, Helga B.

AU - Van Altena, Anne M.

AU - Aben, Katja K H

AU - Kiemeney, Lambartus

AU - Massuger, Leon F A G

AU - Pejovic, Tanja

AU - Bean, Yukie

AU - Brooks-Wilson, Angela

AU - Kelemen, Linda E.

AU - Cook, Linda S.

AU - Le, Nhu D.

AU - Gorski, Bohdan

AU - Gronwald, Jacek

AU - Menkiszak, Janusz

AU - Hogdall, Claus

AU - Lundvall, Lene

AU - Nedergaard, Lotte

AU - Engelholm, Svend Aage

AU - Dicks, Ed

AU - Tyrer, Jonathan

AU - Campbell, Ian

AU - McNeish, Iain A.

AU - Paul, James

AU - Siddiqui, Nadeem

AU - Glasspool, Rosalind

AU - Whittemore, Alice S.

AU - Rothstein, Joseph H.

AU - McGuire, Valerie

AU - Sieh, Weiva

AU - Cai, Hui

AU - Shu, Xiao Ou

AU - Teten, Rachel T.

AU - Sutphen, Rebecca

AU - McLaughlin, John R.

AU - Narod, S. A.

AU - Phelan, Catherine M.

AU - Monteiro, Alvaro N.

AU - Fenstermacher, David A.

AU - Lin, Hui Yi

AU - Permuth, Jennifer B.

AU - Sellers, Thomas A.

AU - Chen, Y. Ann

AU - Tsai, Ya Yu

AU - Chen, Zhihua

AU - Gentry-Maharaj, Aleksandra

AU - Gayther, Simon A.

AU - Ramus, Susan J.

AU - Menon, Usha

AU - Wu, Anna H.

AU - Pearce, Celeste L.

AU - Van Den Berg, David

AU - Pike, Malcolm C.

AU - Dansonka-Mieszkowska, Agnieszka

AU - Plisiecka-Halasa, Joanna

AU - Moes-Sosnowska, Joanna

AU - Kupryjanczyk, Jolanta

AU - Pharoah, Paul D P

AU - Song, Honglin

AU - Winship, Ingrid M.

AU - Chenevix-Trench, Georgia

AU - Giles, Graham G.

AU - Tavtigian, Sean V.

AU - Easton, Douglas F.

AU - Milne, Roger L.

PY - 2016/9/2

Y1 - 2016/9/2

N2 - 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.

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.

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U2 - 10.1136/jmedgenet-2016-103839

DO - 10.1136/jmedgenet-2016-103839

M3 - Article

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

SN - 0022-2593

ER -