BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers

Huong D. Meeks, Honglin Song, Kyriaki Michailidou, Manjeet K. Bolla, Joe Dennis, Qin Wang, Daniel Barrowdale, D. Frost, Lesley McGuffog, Steve Ellis, Bingjian Feng, Saundra S. Buys, John Hopper, Melissa Southey, Andrea Tesoriero, Paul A. James, Fiona Bruinsma, Ian Campbell, Annegien Broeks, Marjanka K. Schmidt & 233 others Frans B. Hogervorst, Matthias W. Beckman, Peter A. Fasching, Olivia Fletcher, Nichola Johnson, Elinor J. Sawyer, E. Riboli, S. Banerjee, Usha Menon, Ian P M Tomlinson, Barbara Burwinkel, Ute Hamann, Frederik Marme, Anja Rudolph, Ramunas Janavicius, Laima Tihomirova, Nadine Tung, Judy E. Garber, Daniel Cramer, Kathryn L. Terry, Elizabeth M. Poole, Shelley S. Tworoger, Cecilia M. Dorfling, Elizabeth J. van Rensburg, Andrew K. Godwin, Pascal Guenel, Therese Truong, Dominique Stoppa-Lyonnet, Francesca Damiola, Sylvie Mazoyer, Olga M. Sinilnikova, Claudine Isaacs, Christine Maugard, Stig E. Bojesen, Henrik Flyger, Anne Marie Gerdes, Thomas v O Hansen, Allen Jensen, Susanne Krüger Kjær, Claus Hogdall, Estrid Hogdall, Inge Sokilde Pedersen, Mads Thomassen, Javier Benitez, Anna González-Neira, Ana Osorio, Miguel De La Hoya, Pedro Perez Segura, Orland Diez, Conxi Lazaro, Joan Brunet, Hoda Anton-Culver, Lee Eunjung, Esther M. John, Susan L. Neuhausen, Yuan Chun Ding, Danielle Castillo, Jeffrey Weitzel, Patricia A. Ganz, Robert L. Nussbaum, Salina Chan, Beth Y. Karlan, Jenny Lester, Anna Wu, Simon A. Gayther, Susan J. Ramus, Weiva Sieh, Alice S. Whittermore, Alvaro N A Monteiro, Catherine M. Phelan, Mary Beth Terry, Marion Piedmonte, Kenneth Offit, Mark E. Robson, Douglas A. Levine, Kirsten B. Moysich, Rikki Cannioto, Sara H. Olson, Mary B. Daly, Katherine L. Nathanson, Susan M. Domchek, Karen H. Lu, Dong Liang, Michelle A T Hildebrant, R. B. Ness, Francesmary Modugno, Leigh Pearce, Marc T. Goodman, Pamela J. Thompson, Hermann Brenner, Katja Butterbach, Alfons Meindl, Eric Hahnen, Barbara Wappenschmidt, Hiltrud Brauch, Thomas Brüning, Carl Blomqvist, Sofia Khan, Heli Nevanlinna, Liisa M. Pelttari, Kristiina Aittomäki, Ralf Butzow, Natalia V. Bogdanova, Thilo Dörk, Annika Lindblom, Sara Margolin, Johanna Rantala, Veli Matti Kosma, Arto Mannermaa, Diether Lambrechts, Patrick Neven, Kathleen Claes, Tom Van Maerken, Jenny Chang-Claude, Dieter Flesch-Janys, Florian Heitz, Raymonda Varon-Mateeva, Paolo Peterlongo, Paolo Radice, Alessandra Viel, Monica Barile, Bernard Gilles Peissel, Siranoush Manoukian, Marco Montagna, Cristina Oliani, Ana Peixoto, Manuel R. Teixeira, Anita Collavoli, Emily Hallberg, Janet E. Olson, Ellen L. Goode, Steven N. Hart, Hermela Shimelis, Julie Cunningham, Graham Giles, Roger L. Milne, Sue Healey, Kathy Tucker, Christopher A. Haiman, Brian E. Henderson, Mark S. Goldberg, Marc Tischkowitz, Jacques Simard, Penny Soucy, Diana Eccles, Nhu Le, Anne Lise Børresen-Dale, Vessela Kristensen, Helga B. Salvesen, Line Bjorge, Elisa V. Bandera, Harvey A. Risch, Wei Zheng, Alicia Beeghly-Fadiel, Hui Cai, Katri Pylkäs, Robert A E M Tollenaar, Ans M W Van Der Ouweland, Irene L. Andrulis, Julia A. Knight, Steven Narod, Peter Devilee, Robert Winqvist, Jonine D. Figueroa, Mark H. Greene, Phuong L. Mai, Jennifer T. Loud, Montse Garcia-Closas, Minouk J. Schoemaker, Kamila Czene, Hatef Darabi, Iain A. McNeish, Nadeem Siddiquil, Rosalind Glasspool, A. Kwong, Sue K. Park, Soo Hwang Teo, Sook Yee Yoon, Keitaro Matsuo, Satoyo Hosono, Yin Ling Woo, Yu Tang Gao, Lenka Foretova, Christian F. Singer, Christine Rappaport-Feurhauser, Eitan Friedman, Yael Laitman, Gad Rennert, Evgeny Imyanitov, Peter J. Hulick, Olufunmilayo I. Olopade, Leigha Senter, Edith Olah, Jennifer A. Doherty, Joellen M. Schildkraut, Linetta B. Koppert, Lambartus Kiemeney, Leon F A G Massuger, Linda S. Cook, Tanja Pejovic, Jingmei Li, Ake Borg, Anna Öfverholm, Mary Anne Rossing, Nicolas Wentzensen, Karin Henriksson, Angela Cox, Simon S. Cross, Barbara Pasini, Mitul Shah, Maria Kabisch, Diana Torres, Anna Jakubowska, Jan Lubinski, Jacek Gronwald, Bjarni A. Agnarsson, Jolanta Kupryjanczyk, Joanna Moes-Sosnowska, Florentia Fostira, Irene Konstantopoulou, Susan Slager, Michael E. Jones, Antonis C. Antoniou, Andrew Berchuck, Anthony J. Swerdlow, Georgia Chenevix-Trench, Alison Dunning, Paul D P Pharoah, Per Hall, Douglas F. Easton, Fergus J. Couch, Amanda B. Spurdle, David Goldgar

Research output: Contribution to journalArticle

Abstract

Background: The K3326X variant in BRCA2 (BRCA2∗c.9976A>T p.Lys3326∗rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormonerelated cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76637 cancer case patients and 83796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9×10-6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8×10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor-negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4×10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1×10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations.

Original languageEnglish
Article numberdjv315
JournalJournal of the National Cancer Institute
Volume108
Issue number2
DOIs
Publication statusPublished - Feb 1 2016

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Terminator Codon
Ovarian Neoplasms
Prostatic Neoplasms
Confidence Intervals
Breast Neoplasms
Mutation
Linkage Disequilibrium
Estrogen Receptors
Neoplasms
Breast
Logistic Models
Odds Ratio
Weights and Measures

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Meeks, H. D., Song, H., Michailidou, K., Bolla, M. K., Dennis, J., Wang, Q., ... Goldgar, D. (2016). BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers. Journal of the National Cancer Institute, 108(2), [djv315]. https://doi.org/10.1093/jnci/djv315

BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers. / Meeks, Huong D.; Song, Honglin; Michailidou, Kyriaki; Bolla, Manjeet K.; Dennis, Joe; Wang, Qin; Barrowdale, Daniel; Frost, D.; McGuffog, Lesley; Ellis, Steve; Feng, Bingjian; Buys, Saundra S.; Hopper, John; Southey, Melissa; Tesoriero, Andrea; James, Paul A.; Bruinsma, Fiona; Campbell, Ian; Broeks, Annegien; Schmidt, Marjanka K.; Hogervorst, Frans B.; Beckman, Matthias W.; Fasching, Peter A.; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor J.; Riboli, E.; Banerjee, S.; Menon, Usha; Tomlinson, Ian P M; Burwinkel, Barbara; Hamann, Ute; Marme, Frederik; Rudolph, Anja; Janavicius, Ramunas; Tihomirova, Laima; Tung, Nadine; Garber, Judy E.; Cramer, Daniel; Terry, Kathryn L.; Poole, Elizabeth M.; Tworoger, Shelley S.; Dorfling, Cecilia M.; van Rensburg, Elizabeth J.; Godwin, Andrew K.; Guenel, Pascal; Truong, Therese; Stoppa-Lyonnet, Dominique; Damiola, Francesca; Mazoyer, Sylvie; Sinilnikova, Olga M.; Isaacs, Claudine; Maugard, Christine; Bojesen, Stig E.; Flyger, Henrik; Gerdes, Anne Marie; Hansen, Thomas v O; Jensen, Allen; Kjær, Susanne Krüger; Hogdall, Claus; Hogdall, Estrid; Pedersen, Inge Sokilde; Thomassen, Mads; Benitez, Javier; González-Neira, Anna; Osorio, Ana; Hoya, Miguel De La; Segura, Pedro Perez; Diez, Orland; Lazaro, Conxi; Brunet, Joan; Anton-Culver, Hoda; Eunjung, Lee; John, Esther M.; Neuhausen, Susan L.; Ding, Yuan Chun; Castillo, Danielle; Weitzel, Jeffrey; Ganz, Patricia A.; Nussbaum, Robert L.; Chan, Salina; Karlan, Beth Y.; Lester, Jenny; Wu, Anna; Gayther, Simon A.; Ramus, Susan J.; Sieh, Weiva; Whittermore, Alice S.; Monteiro, Alvaro N A; Phelan, Catherine M.; Terry, Mary Beth; Piedmonte, Marion; Offit, Kenneth; Robson, Mark E.; Levine, Douglas A.; Moysich, Kirsten B.; Cannioto, Rikki; Olson, Sara H.; Daly, Mary B.; Nathanson, Katherine L.; Domchek, Susan M.; Lu, Karen H.; Liang, Dong; Hildebrant, Michelle A T; Ness, R. B.; Modugno, Francesmary; Pearce, Leigh; Goodman, Marc T.; Thompson, Pamela J.; Brenner, Hermann; Butterbach, Katja; Meindl, Alfons; Hahnen, Eric; Wappenschmidt, Barbara; Brauch, Hiltrud; Brüning, Thomas; Blomqvist, Carl; Khan, Sofia; Nevanlinna, Heli; Pelttari, Liisa M.; Aittomäki, Kristiina; Butzow, Ralf; Bogdanova, Natalia V.; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Rantala, Johanna; Kosma, Veli Matti; Mannermaa, Arto; Lambrechts, Diether; Neven, Patrick; Claes, Kathleen; Van Maerken, Tom; Chang-Claude, Jenny; Flesch-Janys, Dieter; Heitz, Florian; Varon-Mateeva, Raymonda; Peterlongo, Paolo; Radice, Paolo; Viel, Alessandra; Barile, Monica; Peissel, Bernard Gilles; Manoukian, Siranoush; Montagna, Marco; Oliani, Cristina; Peixoto, Ana; Teixeira, Manuel R.; Collavoli, Anita; Hallberg, Emily; Olson, Janet E.; Goode, Ellen L.; Hart, Steven N.; Shimelis, Hermela; Cunningham, Julie; Giles, Graham; Milne, Roger L.; Healey, Sue; Tucker, Kathy; Haiman, Christopher A.; Henderson, Brian E.; Goldberg, Mark S.; Tischkowitz, Marc; Simard, Jacques; Soucy, Penny; Eccles, Diana; Le, Nhu; Børresen-Dale, Anne Lise; Kristensen, Vessela; Salvesen, Helga B.; Bjorge, Line; Bandera, Elisa V.; Risch, Harvey A.; Zheng, Wei; Beeghly-Fadiel, Alicia; Cai, Hui; Pylkäs, Katri; Tollenaar, Robert A E M; Ouweland, Ans M W Van Der; Andrulis, Irene L.; Knight, Julia A.; Narod, Steven; Devilee, Peter; Winqvist, Robert; Figueroa, Jonine D.; Greene, Mark H.; Mai, Phuong L.; Loud, Jennifer T.; Garcia-Closas, Montse; Schoemaker, Minouk J.; Czene, Kamila; Darabi, Hatef; McNeish, Iain A.; Siddiquil, Nadeem; Glasspool, Rosalind; Kwong, A.; Park, Sue K.; Teo, Soo Hwang; Yoon, Sook Yee; Matsuo, Keitaro; Hosono, Satoyo; Woo, Yin Ling; Gao, Yu Tang; Foretova, Lenka; Singer, Christian F.; Rappaport-Feurhauser, Christine; Friedman, Eitan; Laitman, Yael; Rennert, Gad; Imyanitov, Evgeny; Hulick, Peter J.; Olopade, Olufunmilayo I.; Senter, Leigha; Olah, Edith; Doherty, Jennifer A.; Schildkraut, Joellen M.; Koppert, Linetta B.; Kiemeney, Lambartus; Massuger, Leon F A G; Cook, Linda S.; Pejovic, Tanja; Li, Jingmei; Borg, Ake; Öfverholm, Anna; Rossing, Mary Anne; Wentzensen, Nicolas; Henriksson, Karin; Cox, Angela; Cross, Simon S.; Pasini, Barbara; Shah, Mitul; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Gronwald, Jacek; Agnarsson, Bjarni A.; Kupryjanczyk, Jolanta; Moes-Sosnowska, Joanna; Fostira, Florentia; Konstantopoulou, Irene; Slager, Susan; Jones, Michael E.; Antoniou, Antonis C.; Berchuck, Andrew; Swerdlow, Anthony J.; Chenevix-Trench, Georgia; Dunning, Alison; Pharoah, Paul D P; Hall, Per; Easton, Douglas F.; Couch, Fergus J.; Spurdle, Amanda B.; Goldgar, David.

In: Journal of the National Cancer Institute, Vol. 108, No. 2, djv315, 01.02.2016.

Research output: Contribution to journalArticle

Meeks, HD, Song, H, Michailidou, K, Bolla, MK, Dennis, J, Wang, Q, Barrowdale, D, Frost, D, McGuffog, L, Ellis, S, Feng, B, Buys, SS, Hopper, J, Southey, M, Tesoriero, A, James, PA, Bruinsma, F, Campbell, I, Broeks, A, Schmidt, MK, Hogervorst, FB, Beckman, MW, Fasching, PA, Fletcher, O, Johnson, N, Sawyer, EJ, Riboli, E, Banerjee, S, Menon, U, Tomlinson, IPM, Burwinkel, B, Hamann, U, Marme, F, Rudolph, A, Janavicius, R, Tihomirova, L, Tung, N, Garber, JE, Cramer, D, Terry, KL, Poole, EM, Tworoger, SS, Dorfling, CM, van Rensburg, EJ, Godwin, AK, Guenel, P, Truong, T, Stoppa-Lyonnet, D, Damiola, F, Mazoyer, S, Sinilnikova, OM, Isaacs, C, Maugard, C, Bojesen, SE, Flyger, H, Gerdes, AM, Hansen, TVO, Jensen, A, Kjær, SK, Hogdall, C, Hogdall, E, Pedersen, IS, Thomassen, M, Benitez, J, González-Neira, A, Osorio, A, Hoya, MDL, Segura, PP, Diez, O, Lazaro, C, Brunet, J, Anton-Culver, H, Eunjung, L, John, EM, Neuhausen, SL, Ding, YC, Castillo, D, Weitzel, J, Ganz, PA, Nussbaum, RL, Chan, S, Karlan, BY, Lester, J, Wu, A, Gayther, SA, Ramus, SJ, Sieh, W, Whittermore, AS, Monteiro, ANA, Phelan, CM, Terry, MB, Piedmonte, M, Offit, K, Robson, ME, Levine, DA, Moysich, KB, Cannioto, R, Olson, SH, Daly, MB, Nathanson, KL, Domchek, SM, Lu, KH, Liang, D, Hildebrant, MAT, Ness, RB, Modugno, F, Pearce, L, Goodman, MT, Thompson, PJ, Brenner, H, Butterbach, K, Meindl, A, Hahnen, E, Wappenschmidt, B, Brauch, H, Brüning, T, Blomqvist, C, Khan, S, Nevanlinna, H, Pelttari, LM, Aittomäki, K, Butzow, R, Bogdanova, NV, Dörk, T, Lindblom, A, Margolin, S, Rantala, J, Kosma, VM, Mannermaa, A, Lambrechts, D, Neven, P, Claes, K, Van Maerken, T, Chang-Claude, J, Flesch-Janys, D, Heitz, F, Varon-Mateeva, R, Peterlongo, P, Radice, P, Viel, A, Barile, M, Peissel, BG, Manoukian, S, Montagna, M, Oliani, C, Peixoto, A, Teixeira, MR, Collavoli, A, Hallberg, E, Olson, JE, Goode, EL, Hart, SN, Shimelis, H, Cunningham, J, Giles, G, Milne, RL, Healey, S, Tucker, K, Haiman, CA, Henderson, BE, Goldberg, MS, Tischkowitz, M, Simard, J, Soucy, P, Eccles, D, Le, N, Børresen-Dale, AL, Kristensen, V, Salvesen, HB, Bjorge, L, Bandera, EV, Risch, HA, Zheng, W, Beeghly-Fadiel, A, Cai, H, Pylkäs, K, Tollenaar, RAEM, Ouweland, AMWVD, Andrulis, IL, Knight, JA, Narod, S, Devilee, P, Winqvist, R, Figueroa, JD, Greene, MH, Mai, PL, Loud, JT, Garcia-Closas, M, Schoemaker, MJ, Czene, K, Darabi, H, McNeish, IA, Siddiquil, N, Glasspool, R, Kwong, A, Park, SK, Teo, SH, Yoon, SY, Matsuo, K, Hosono, S, Woo, YL, Gao, YT, Foretova, L, Singer, CF, Rappaport-Feurhauser, C, Friedman, E, Laitman, Y, Rennert, G, Imyanitov, E, Hulick, PJ, Olopade, OI, Senter, L, Olah, E, Doherty, JA, Schildkraut, JM, Koppert, LB, Kiemeney, L, Massuger, LFAG, Cook, LS, Pejovic, T, Li, J, Borg, A, Öfverholm, A, Rossing, MA, Wentzensen, N, Henriksson, K, Cox, A, Cross, SS, Pasini, B, Shah, M, Kabisch, M, Torres, D, Jakubowska, A, Lubinski, J, Gronwald, J, Agnarsson, BA, Kupryjanczyk, J, Moes-Sosnowska, J, Fostira, F, Konstantopoulou, I, Slager, S, Jones, ME, Antoniou, AC, Berchuck, A, Swerdlow, AJ, Chenevix-Trench, G, Dunning, A, Pharoah, PDP, Hall, P, Easton, DF, Couch, FJ, Spurdle, AB & Goldgar, D 2016, 'BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers', Journal of the National Cancer Institute, vol. 108, no. 2, djv315. https://doi.org/10.1093/jnci/djv315
Meeks, Huong D. ; Song, Honglin ; Michailidou, Kyriaki ; Bolla, Manjeet K. ; Dennis, Joe ; Wang, Qin ; Barrowdale, Daniel ; Frost, D. ; McGuffog, Lesley ; Ellis, Steve ; Feng, Bingjian ; Buys, Saundra S. ; Hopper, John ; Southey, Melissa ; Tesoriero, Andrea ; James, Paul A. ; Bruinsma, Fiona ; Campbell, Ian ; Broeks, Annegien ; Schmidt, Marjanka K. ; Hogervorst, Frans B. ; Beckman, Matthias W. ; Fasching, Peter A. ; Fletcher, Olivia ; Johnson, Nichola ; Sawyer, Elinor J. ; Riboli, E. ; Banerjee, S. ; Menon, Usha ; Tomlinson, Ian P M ; Burwinkel, Barbara ; Hamann, Ute ; Marme, Frederik ; Rudolph, Anja ; Janavicius, Ramunas ; Tihomirova, Laima ; Tung, Nadine ; Garber, Judy E. ; Cramer, Daniel ; Terry, Kathryn L. ; Poole, Elizabeth M. ; Tworoger, Shelley S. ; Dorfling, Cecilia M. ; van Rensburg, Elizabeth J. ; Godwin, Andrew K. ; Guenel, Pascal ; Truong, Therese ; Stoppa-Lyonnet, Dominique ; Damiola, Francesca ; Mazoyer, Sylvie ; Sinilnikova, Olga M. ; Isaacs, Claudine ; Maugard, Christine ; Bojesen, Stig E. ; Flyger, Henrik ; Gerdes, Anne Marie ; Hansen, Thomas v O ; Jensen, Allen ; Kjær, Susanne Krüger ; Hogdall, Claus ; Hogdall, Estrid ; Pedersen, Inge Sokilde ; Thomassen, Mads ; Benitez, Javier ; González-Neira, Anna ; Osorio, Ana ; Hoya, Miguel De La ; Segura, Pedro Perez ; Diez, Orland ; Lazaro, Conxi ; Brunet, Joan ; Anton-Culver, Hoda ; Eunjung, Lee ; John, Esther M. ; Neuhausen, Susan L. ; Ding, Yuan Chun ; Castillo, Danielle ; Weitzel, Jeffrey ; Ganz, Patricia A. ; Nussbaum, Robert L. ; Chan, Salina ; Karlan, Beth Y. ; Lester, Jenny ; Wu, Anna ; Gayther, Simon A. ; Ramus, Susan J. ; Sieh, Weiva ; Whittermore, Alice S. ; Monteiro, Alvaro N A ; Phelan, Catherine M. ; Terry, Mary Beth ; Piedmonte, Marion ; Offit, Kenneth ; Robson, Mark E. ; Levine, Douglas A. ; Moysich, Kirsten B. ; Cannioto, Rikki ; Olson, Sara H. ; Daly, Mary B. ; Nathanson, Katherine L. ; Domchek, Susan M. ; Lu, Karen H. ; Liang, Dong ; Hildebrant, Michelle A T ; Ness, R. B. ; Modugno, Francesmary ; Pearce, Leigh ; Goodman, Marc T. ; Thompson, Pamela J. ; Brenner, Hermann ; Butterbach, Katja ; Meindl, Alfons ; Hahnen, Eric ; Wappenschmidt, Barbara ; Brauch, Hiltrud ; Brüning, Thomas ; Blomqvist, Carl ; Khan, Sofia ; Nevanlinna, Heli ; Pelttari, Liisa M. ; Aittomäki, Kristiina ; Butzow, Ralf ; Bogdanova, Natalia V. ; Dörk, Thilo ; Lindblom, Annika ; Margolin, Sara ; Rantala, Johanna ; Kosma, Veli Matti ; Mannermaa, Arto ; Lambrechts, Diether ; Neven, Patrick ; Claes, Kathleen ; Van Maerken, Tom ; Chang-Claude, Jenny ; Flesch-Janys, Dieter ; Heitz, Florian ; Varon-Mateeva, Raymonda ; Peterlongo, Paolo ; Radice, Paolo ; Viel, Alessandra ; Barile, Monica ; Peissel, Bernard Gilles ; Manoukian, Siranoush ; Montagna, Marco ; Oliani, Cristina ; Peixoto, Ana ; Teixeira, Manuel R. ; Collavoli, Anita ; Hallberg, Emily ; Olson, Janet E. ; Goode, Ellen L. ; Hart, Steven N. ; Shimelis, Hermela ; Cunningham, Julie ; Giles, Graham ; Milne, Roger L. ; Healey, Sue ; Tucker, Kathy ; Haiman, Christopher A. ; Henderson, Brian E. ; Goldberg, Mark S. ; Tischkowitz, Marc ; Simard, Jacques ; Soucy, Penny ; Eccles, Diana ; Le, Nhu ; Børresen-Dale, Anne Lise ; Kristensen, Vessela ; Salvesen, Helga B. ; Bjorge, Line ; Bandera, Elisa V. ; Risch, Harvey A. ; Zheng, Wei ; Beeghly-Fadiel, Alicia ; Cai, Hui ; Pylkäs, Katri ; Tollenaar, Robert A E M ; Ouweland, Ans M W Van Der ; Andrulis, Irene L. ; Knight, Julia A. ; Narod, Steven ; Devilee, Peter ; Winqvist, Robert ; Figueroa, Jonine D. ; Greene, Mark H. ; Mai, Phuong L. ; Loud, Jennifer T. ; Garcia-Closas, Montse ; Schoemaker, Minouk J. ; Czene, Kamila ; Darabi, Hatef ; McNeish, Iain A. ; Siddiquil, Nadeem ; Glasspool, Rosalind ; Kwong, A. ; Park, Sue K. ; Teo, Soo Hwang ; Yoon, Sook Yee ; Matsuo, Keitaro ; Hosono, Satoyo ; Woo, Yin Ling ; Gao, Yu Tang ; Foretova, Lenka ; Singer, Christian F. ; Rappaport-Feurhauser, Christine ; Friedman, Eitan ; Laitman, Yael ; Rennert, Gad ; Imyanitov, Evgeny ; Hulick, Peter J. ; Olopade, Olufunmilayo I. ; Senter, Leigha ; Olah, Edith ; Doherty, Jennifer A. ; Schildkraut, Joellen M. ; Koppert, Linetta B. ; Kiemeney, Lambartus ; Massuger, Leon F A G ; Cook, Linda S. ; Pejovic, Tanja ; Li, Jingmei ; Borg, Ake ; Öfverholm, Anna ; Rossing, Mary Anne ; Wentzensen, Nicolas ; Henriksson, Karin ; Cox, Angela ; Cross, Simon S. ; Pasini, Barbara ; Shah, Mitul ; Kabisch, Maria ; Torres, Diana ; Jakubowska, Anna ; Lubinski, Jan ; Gronwald, Jacek ; Agnarsson, Bjarni A. ; Kupryjanczyk, Jolanta ; Moes-Sosnowska, Joanna ; Fostira, Florentia ; Konstantopoulou, Irene ; Slager, Susan ; Jones, Michael E. ; Antoniou, Antonis C. ; Berchuck, Andrew ; Swerdlow, Anthony J. ; Chenevix-Trench, Georgia ; Dunning, Alison ; Pharoah, Paul D P ; Hall, Per ; Easton, Douglas F. ; Couch, Fergus J. ; Spurdle, Amanda B. ; Goldgar, David. / BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers. In: Journal of the National Cancer Institute. 2016 ; Vol. 108, No. 2.
@article{c737ba53f76f45eaa9b6a6a8d45f83e7,
title = "BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers",
abstract = "Background: The K3326X variant in BRCA2 (BRCA2∗c.9976A>T p.Lys3326∗rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormonerelated cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76637 cancer case patients and 83796 control patients to estimate odds ratios (ORw) and 95{\%} confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95{\%} CI = 1.17 to 1.40, P = 5.9×10-6) and invasive ovarian cancer (ORw = 1.26, 95{\%} CI = 1.10 to 1.43, P = 3.8×10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor-negative breast cancer (ORw = 1.46, 95{\%} CI = 1.2 to 1.70, P = 3.4×10-5 and ORw = 1.50, 95{\%} CI = 1.28 to 1.76, P = 4.1×10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95{\%} CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations.",
author = "Meeks, {Huong D.} and Honglin Song and Kyriaki Michailidou and Bolla, {Manjeet K.} and Joe Dennis and Qin Wang and Daniel Barrowdale and D. Frost and Lesley McGuffog and Steve Ellis and Bingjian Feng and Buys, {Saundra S.} and John Hopper and Melissa Southey and Andrea Tesoriero and James, {Paul A.} and Fiona Bruinsma and Ian Campbell and Annegien Broeks and Schmidt, {Marjanka K.} and Hogervorst, {Frans B.} and Beckman, {Matthias W.} and Fasching, {Peter A.} and Olivia Fletcher and Nichola Johnson and Sawyer, {Elinor J.} and E. Riboli and S. Banerjee and Usha Menon and Tomlinson, {Ian P M} and Barbara Burwinkel and Ute Hamann and Frederik Marme and Anja Rudolph and Ramunas Janavicius and Laima Tihomirova and Nadine Tung and Garber, {Judy E.} and Daniel Cramer and Terry, {Kathryn L.} and Poole, {Elizabeth M.} and Tworoger, {Shelley S.} and Dorfling, {Cecilia M.} and {van Rensburg}, {Elizabeth J.} and Godwin, {Andrew K.} and Pascal Guenel and Therese Truong and Dominique Stoppa-Lyonnet and Francesca Damiola and Sylvie Mazoyer and Sinilnikova, {Olga M.} and Claudine Isaacs and Christine Maugard and Bojesen, {Stig E.} and Henrik Flyger and Gerdes, {Anne Marie} and Hansen, {Thomas v O} and Allen Jensen and Kj{\ae}r, {Susanne Kr{\"u}ger} and Claus Hogdall and Estrid Hogdall and Pedersen, {Inge Sokilde} and Mads Thomassen and Javier Benitez and Anna Gonz{\'a}lez-Neira and Ana Osorio and Hoya, {Miguel De La} and Segura, {Pedro Perez} and Orland Diez and Conxi Lazaro and Joan Brunet and Hoda Anton-Culver and Lee Eunjung and John, {Esther M.} and Neuhausen, {Susan L.} and Ding, {Yuan Chun} and Danielle Castillo and Jeffrey Weitzel and Ganz, {Patricia A.} and Nussbaum, {Robert L.} and Salina Chan and Karlan, {Beth Y.} and Jenny Lester and Anna Wu and Gayther, {Simon A.} and Ramus, {Susan J.} and Weiva Sieh and Whittermore, {Alice S.} and Monteiro, {Alvaro N A} and Phelan, {Catherine M.} and Terry, {Mary Beth} and Marion Piedmonte and Kenneth Offit and Robson, {Mark E.} and Levine, {Douglas A.} and Moysich, {Kirsten B.} and Rikki Cannioto and Olson, {Sara H.} and Daly, {Mary B.} and Nathanson, {Katherine L.} and Domchek, {Susan M.} and Lu, {Karen H.} and Dong Liang and Hildebrant, {Michelle A T} and Ness, {R. B.} and Francesmary Modugno and Leigh Pearce and Goodman, {Marc T.} and Thompson, {Pamela J.} and Hermann Brenner and Katja Butterbach and Alfons Meindl and Eric Hahnen and Barbara Wappenschmidt and Hiltrud Brauch and Thomas Br{\"u}ning and Carl Blomqvist and Sofia Khan and Heli Nevanlinna and Pelttari, {Liisa M.} and Kristiina Aittom{\"a}ki and Ralf Butzow and Bogdanova, {Natalia V.} and Thilo D{\"o}rk and Annika Lindblom and Sara Margolin and Johanna Rantala and Kosma, {Veli Matti} and Arto Mannermaa and Diether Lambrechts and Patrick Neven and Kathleen Claes and {Van Maerken}, Tom and Jenny Chang-Claude and Dieter Flesch-Janys and Florian Heitz and Raymonda Varon-Mateeva and Paolo Peterlongo and Paolo Radice and Alessandra Viel and Monica Barile and Peissel, {Bernard Gilles} and Siranoush Manoukian and Marco Montagna and Cristina Oliani and Ana Peixoto and Teixeira, {Manuel R.} and Anita Collavoli and Emily Hallberg and Olson, {Janet E.} and Goode, {Ellen L.} and Hart, {Steven N.} and Hermela Shimelis and Julie Cunningham and Graham Giles and Milne, {Roger L.} and Sue Healey and Kathy Tucker and Haiman, {Christopher A.} and Henderson, {Brian E.} and Goldberg, {Mark S.} and Marc Tischkowitz and Jacques Simard and Penny Soucy and Diana Eccles and Nhu Le and B{\o}rresen-Dale, {Anne Lise} and Vessela Kristensen and Salvesen, {Helga B.} and Line Bjorge and Bandera, {Elisa V.} and Risch, {Harvey A.} and Wei Zheng and Alicia Beeghly-Fadiel and Hui Cai and Katri Pylk{\"a}s and Tollenaar, {Robert A E M} and Ouweland, {Ans M W Van Der} and Andrulis, {Irene L.} and Knight, {Julia A.} and Steven Narod and Peter Devilee and Robert Winqvist and Figueroa, {Jonine D.} and Greene, {Mark H.} and Mai, {Phuong L.} and Loud, {Jennifer T.} and Montse Garcia-Closas and Schoemaker, {Minouk J.} and Kamila Czene and Hatef Darabi and McNeish, {Iain A.} and Nadeem Siddiquil and Rosalind Glasspool and A. Kwong and Park, {Sue K.} and Teo, {Soo Hwang} and Yoon, {Sook Yee} and Keitaro Matsuo and Satoyo Hosono and Woo, {Yin Ling} and Gao, {Yu Tang} and Lenka Foretova and Singer, {Christian F.} and Christine Rappaport-Feurhauser and Eitan Friedman and Yael Laitman and Gad Rennert and Evgeny Imyanitov and Hulick, {Peter J.} and Olopade, {Olufunmilayo I.} and Leigha Senter and Edith Olah and Doherty, {Jennifer A.} and Schildkraut, {Joellen M.} and Koppert, {Linetta B.} and Lambartus Kiemeney and Massuger, {Leon F A G} and Cook, {Linda S.} and Tanja Pejovic and Jingmei Li and Ake Borg and Anna {\"O}fverholm and Rossing, {Mary Anne} and Nicolas Wentzensen and Karin Henriksson and Angela Cox and Cross, {Simon S.} and Barbara Pasini and Mitul Shah and Maria Kabisch and Diana Torres and Anna Jakubowska and Jan Lubinski and Jacek Gronwald and Agnarsson, {Bjarni A.} and Jolanta Kupryjanczyk and Joanna Moes-Sosnowska and Florentia Fostira and Irene Konstantopoulou and Susan Slager and Jones, {Michael E.} and Antoniou, {Antonis C.} and Andrew Berchuck and Swerdlow, {Anthony J.} and Georgia Chenevix-Trench and Alison Dunning and Pharoah, {Paul D P} and Per Hall and Easton, {Douglas F.} and Couch, {Fergus J.} and Spurdle, {Amanda B.} and David Goldgar",
year = "2016",
month = "2",
day = "1",
doi = "10.1093/jnci/djv315",
language = "English",
volume = "108",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers

AU - Meeks, Huong D.

AU - Song, Honglin

AU - Michailidou, Kyriaki

AU - Bolla, Manjeet K.

AU - Dennis, Joe

AU - Wang, Qin

AU - Barrowdale, Daniel

AU - Frost, D.

AU - McGuffog, Lesley

AU - Ellis, Steve

AU - Feng, Bingjian

AU - Buys, Saundra S.

AU - Hopper, John

AU - Southey, Melissa

AU - Tesoriero, Andrea

AU - James, Paul A.

AU - Bruinsma, Fiona

AU - Campbell, Ian

AU - Broeks, Annegien

AU - Schmidt, Marjanka K.

AU - Hogervorst, Frans B.

AU - Beckman, Matthias W.

AU - Fasching, Peter A.

AU - Fletcher, Olivia

AU - Johnson, Nichola

AU - Sawyer, Elinor J.

AU - Riboli, E.

AU - Banerjee, S.

AU - Menon, Usha

AU - Tomlinson, Ian P M

AU - Burwinkel, Barbara

AU - Hamann, Ute

AU - Marme, Frederik

AU - Rudolph, Anja

AU - Janavicius, Ramunas

AU - Tihomirova, Laima

AU - Tung, Nadine

AU - Garber, Judy E.

AU - Cramer, Daniel

AU - Terry, Kathryn L.

AU - Poole, Elizabeth M.

AU - Tworoger, Shelley S.

AU - Dorfling, Cecilia M.

AU - van Rensburg, Elizabeth J.

AU - Godwin, Andrew K.

AU - Guenel, Pascal

AU - Truong, Therese

AU - Stoppa-Lyonnet, Dominique

AU - Damiola, Francesca

AU - Mazoyer, Sylvie

AU - Sinilnikova, Olga M.

AU - Isaacs, Claudine

AU - Maugard, Christine

AU - Bojesen, Stig E.

AU - Flyger, Henrik

AU - Gerdes, Anne Marie

AU - Hansen, Thomas v O

AU - Jensen, Allen

AU - Kjær, Susanne Krüger

AU - Hogdall, Claus

AU - Hogdall, Estrid

AU - Pedersen, Inge Sokilde

AU - Thomassen, Mads

AU - Benitez, Javier

AU - González-Neira, Anna

AU - Osorio, Ana

AU - Hoya, Miguel De La

AU - Segura, Pedro Perez

AU - Diez, Orland

AU - Lazaro, Conxi

AU - Brunet, Joan

AU - Anton-Culver, Hoda

AU - Eunjung, Lee

AU - John, Esther M.

AU - Neuhausen, Susan L.

AU - Ding, Yuan Chun

AU - Castillo, Danielle

AU - Weitzel, Jeffrey

AU - Ganz, Patricia A.

AU - Nussbaum, Robert L.

AU - Chan, Salina

AU - Karlan, Beth Y.

AU - Lester, Jenny

AU - Wu, Anna

AU - Gayther, Simon A.

AU - Ramus, Susan J.

AU - Sieh, Weiva

AU - Whittermore, Alice S.

AU - Monteiro, Alvaro N A

AU - Phelan, Catherine M.

AU - Terry, Mary Beth

AU - Piedmonte, Marion

AU - Offit, Kenneth

AU - Robson, Mark E.

AU - Levine, Douglas A.

AU - Moysich, Kirsten B.

AU - Cannioto, Rikki

AU - Olson, Sara H.

AU - Daly, Mary B.

AU - Nathanson, Katherine L.

AU - Domchek, Susan M.

AU - Lu, Karen H.

AU - Liang, Dong

AU - Hildebrant, Michelle A T

AU - Ness, R. B.

AU - Modugno, Francesmary

AU - Pearce, Leigh

AU - Goodman, Marc T.

AU - Thompson, Pamela J.

AU - Brenner, Hermann

AU - Butterbach, Katja

AU - Meindl, Alfons

AU - Hahnen, Eric

AU - Wappenschmidt, Barbara

AU - Brauch, Hiltrud

AU - Brüning, Thomas

AU - Blomqvist, Carl

AU - Khan, Sofia

AU - Nevanlinna, Heli

AU - Pelttari, Liisa M.

AU - Aittomäki, Kristiina

AU - Butzow, Ralf

AU - Bogdanova, Natalia V.

AU - Dörk, Thilo

AU - Lindblom, Annika

AU - Margolin, Sara

AU - Rantala, Johanna

AU - Kosma, Veli Matti

AU - Mannermaa, Arto

AU - Lambrechts, Diether

AU - Neven, Patrick

AU - Claes, Kathleen

AU - Van Maerken, Tom

AU - Chang-Claude, Jenny

AU - Flesch-Janys, Dieter

AU - Heitz, Florian

AU - Varon-Mateeva, Raymonda

AU - Peterlongo, Paolo

AU - Radice, Paolo

AU - Viel, Alessandra

AU - Barile, Monica

AU - Peissel, Bernard Gilles

AU - Manoukian, Siranoush

AU - Montagna, Marco

AU - Oliani, Cristina

AU - Peixoto, Ana

AU - Teixeira, Manuel R.

AU - Collavoli, Anita

AU - Hallberg, Emily

AU - Olson, Janet E.

AU - Goode, Ellen L.

AU - Hart, Steven N.

AU - Shimelis, Hermela

AU - Cunningham, Julie

AU - Giles, Graham

AU - Milne, Roger L.

AU - Healey, Sue

AU - Tucker, Kathy

AU - Haiman, Christopher A.

AU - Henderson, Brian E.

AU - Goldberg, Mark S.

AU - Tischkowitz, Marc

AU - Simard, Jacques

AU - Soucy, Penny

AU - Eccles, Diana

AU - Le, Nhu

AU - Børresen-Dale, Anne Lise

AU - Kristensen, Vessela

AU - Salvesen, Helga B.

AU - Bjorge, Line

AU - Bandera, Elisa V.

AU - Risch, Harvey A.

AU - Zheng, Wei

AU - Beeghly-Fadiel, Alicia

AU - Cai, Hui

AU - Pylkäs, Katri

AU - Tollenaar, Robert A E M

AU - Ouweland, Ans M W Van Der

AU - Andrulis, Irene L.

AU - Knight, Julia A.

AU - Narod, Steven

AU - Devilee, Peter

AU - Winqvist, Robert

AU - Figueroa, Jonine D.

AU - Greene, Mark H.

AU - Mai, Phuong L.

AU - Loud, Jennifer T.

AU - Garcia-Closas, Montse

AU - Schoemaker, Minouk J.

AU - Czene, Kamila

AU - Darabi, Hatef

AU - McNeish, Iain A.

AU - Siddiquil, Nadeem

AU - Glasspool, Rosalind

AU - Kwong, A.

AU - Park, Sue K.

AU - Teo, Soo Hwang

AU - Yoon, Sook Yee

AU - Matsuo, Keitaro

AU - Hosono, Satoyo

AU - Woo, Yin Ling

AU - Gao, Yu Tang

AU - Foretova, Lenka

AU - Singer, Christian F.

AU - Rappaport-Feurhauser, Christine

AU - Friedman, Eitan

AU - Laitman, Yael

AU - Rennert, Gad

AU - Imyanitov, Evgeny

AU - Hulick, Peter J.

AU - Olopade, Olufunmilayo I.

AU - Senter, Leigha

AU - Olah, Edith

AU - Doherty, Jennifer A.

AU - Schildkraut, Joellen M.

AU - Koppert, Linetta B.

AU - Kiemeney, Lambartus

AU - Massuger, Leon F A G

AU - Cook, Linda S.

AU - Pejovic, Tanja

AU - Li, Jingmei

AU - Borg, Ake

AU - Öfverholm, Anna

AU - Rossing, Mary Anne

AU - Wentzensen, Nicolas

AU - Henriksson, Karin

AU - Cox, Angela

AU - Cross, Simon S.

AU - Pasini, Barbara

AU - Shah, Mitul

AU - Kabisch, Maria

AU - Torres, Diana

AU - Jakubowska, Anna

AU - Lubinski, Jan

AU - Gronwald, Jacek

AU - Agnarsson, Bjarni A.

AU - Kupryjanczyk, Jolanta

AU - Moes-Sosnowska, Joanna

AU - Fostira, Florentia

AU - Konstantopoulou, Irene

AU - Slager, Susan

AU - Jones, Michael E.

AU - Antoniou, Antonis C.

AU - Berchuck, Andrew

AU - Swerdlow, Anthony J.

AU - Chenevix-Trench, Georgia

AU - Dunning, Alison

AU - Pharoah, Paul D P

AU - Hall, Per

AU - Easton, Douglas F.

AU - Couch, Fergus J.

AU - Spurdle, Amanda B.

AU - Goldgar, David

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Background: The K3326X variant in BRCA2 (BRCA2∗c.9976A>T p.Lys3326∗rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormonerelated cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76637 cancer case patients and 83796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9×10-6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8×10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor-negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4×10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1×10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations.

AB - Background: The K3326X variant in BRCA2 (BRCA2∗c.9976A>T p.Lys3326∗rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormonerelated cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76637 cancer case patients and 83796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9×10-6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8×10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor-negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4×10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1×10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations.

UR - http://www.scopus.com/inward/record.url?scp=84962488384&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962488384&partnerID=8YFLogxK

U2 - 10.1093/jnci/djv315

DO - 10.1093/jnci/djv315

M3 - Article

VL - 108

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 2

M1 - djv315

ER -