Citations 7
Association of the CHEK2 c. 1100delC variant, radiotherapy, and systemic treatment with contralateral b
Morra, Anna , Schreurs, Maartje A. C. , Andrulis, Irene L. , Anton‐Culver, Hoda , Beckmann, Matthias W. , Bolla, Manjeet K. , Camp, Nicola J. , Cessna, Melissa H., Chang‐Claude, Jenny , Collaborators, NBCS, Dörk, Thilo , Easton, Douglas F. , Eccles, Diana M., Evans, D. Gareth , Fasching, Peter A. , Flyger, Henrik, García‐Closas, Montserrat , Graßmann, Felix , Gündert, Melanie , Hahnen, Eric , Haiman, Christopher A. , Hamann, Ute, Harrington, Patricia, Hoppe, Reiner , Hopper, John L. , Houlston, Richard S. , Howell, Anthony, Investigators, ABCTB, Investigators, kConFab, Janni, Wolfgang, John, Esther M. , Johnson, Nichola , Jones, Michael E. , Kristensen, Vessela N. , Kurian, Allison W. , Lambrechts, Diether , Lindblom, Annika , Mannermaa, Arto, Mavroudis, Dimitrios, Muranen, Taru , Nevelsteen, Ines, Neven, Patrick , Newman, William G. , Obi, Nadia , Offit, Kenneth , Park‐Simon, Tjoung‐Won , Patel, Alpa V. , Peterlongo, Paolo , Phillips, Kelly‐Anne , Plaseska‐Karanfilska, Dijana , Rack, Brigitte , Rhenius, Valerie , Romero, Atocha , Sawyer, Elinor J. , Schmutzler, Rita K. , Schuetze, Sabine, Shah, Mitul , Smichkoska, Snezhana , Tollenaar, Rob A.�E.�M. , Tomlinson, Ian , Vachon, Celine M. , Veen, Elke M. van , Wang, Qin , Wendt, Camilla, Wildiers, Hans , Pharoah, Paul D.P. , Adank, Muriel A. , Hooning, Maartje J. , Howell, Anthony , Ramus, Susan J. , Bojesen, Stig E. , Eccles, Diana , Cummings, Margaret C. , Loi, Sherene , Lambrechts, Diether , Howell, Sacha J. , Bojesen, Stig E , Dörk, Thilo , Figueroa, Jonine D , Gabrielson, Marike , Gago-Dominguez, Manuela , García-Sáenz, José A , Hahnen, Eric , Hartikainen, Jaana M , Jernström, Helena , John, Esther M , Lambrechts, Diether , Muranen, Taru A , Nevanlinna, H , Patel, Alpa V , Pylkäs, Katri , Rashid, Muhammad U , Hooning, Maartje J. , Lambrechts, Diether , Peterlongo, Paolo , Ramus, Susan J , Pharoah, Paul D P , Eccles, Diana , Houlston, Richard S , Anton-Culver, Hoda , Evans, D Gareth , Jones, Michael E , Newman, William G , Romero, Atocha , García-Closas, Montserrat , Kurian, Allison W , Loi, Sherene , Bojesen, Stig E , Phillips, Kelly-Anne , Wildiers, Hans , Lindblom, Annika , Plaseska-Karanfilska, Dijana , Sawyer, Elinor J , Augustinsson, Annelie , Behrens, Sabine , Brauch, Hiltrud , Broeks, Annegien , Buys, Saundra S. , Castelao, Jose E. , Chung, Wendy K. , Collaborators, NBCS, Colonna, Sarah V. , Couch, Fergus J. , Cox, Angela , Cross, Simon S. , Czene, Kamila , Daly, Mary Beryl , Dennis, Joe , Devilee, Peter , Dunning, Alison M. , Dwek, Miriam , Eriksson, Mikael , Fehm, Tanja , Figueroa, Jonine D. , Gabrielson, Marike , Gago-Domínguez, Manuela , García-Sáenz, José Á. , Genkinger, Jeanine M. , Hartikainen, Jaana M. , Howell, Anthony, Investigators, ABCTB, Investigators, kConFab, Jakubowska, Anna , Jernström, Helena , Marchand, Loı̈c Le , Lubiński, Jan , Lux, Michael P. , Mannermaa, Arto, Mulligan, Anna Marie , Nevanlinna, Heli , Olshan, Andrew F. , Polley, Eric C. , Presneau, Nadège , Pylkäs, Katri , Radice, Paolo , Rashid, Muhammad Usman , Robson, Mark E. , Saloustros, Emmanouil , Scott, Christopher G. , Southey, Melissa C. , Tapper, William , Teras, Lauren R. , Tomczyk, Katarzyna , Troester, Melissa A. , Vachon, Celine M. , Winqvist, Robert , Ziogas, Argyrios , Hall, Per N , Hollestelle, Antoinette , Schmidt, Marjanka K.
Cancer Medicine | July 4, 2023 | Volume: 12 | Issue: 15 | Pages: 16142-16162
Abstract Background Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC‐specific survival (BCSS) compared to non‐carriers. Aim To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Methods Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow‐up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi‐state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. Results There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55–0.78)]. No association was observed with radiotherapy. Results from the multi‐state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non‐carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09–1.56)]. Conclusion Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk.
Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival
Morra, Anna , Andrulis, Irene L. , Beckmann, Matthias W. , Bolla, Manjeet K. , Camp, Nicola J. , Cessna, Melissa H., Chang‐Claude, Jenny , Collaborators, NBCS, Daly, Mary B., Easton, Douglas F. , Eccles, Diana M., Evans, D. Gareth , Fasching, Peter A. , Flyger, Henrik, García‐Closas, Montserrat , Gündert, Melanie , Hahnen, Eric , Haiman, Christopher A. , Hamann, Ute, Harrington, Patricia, Hoppe, Reiner , Howell, Anthony , Investigators, ABCTB, Investigators, kConFab, Janni, Wolfgang, Johnson, Nichola , Kristensen, Vessela N. , Lindblom, Annika , Mannermaa, Arto , Mavroudis, Dimitrios, Nevelsteen, Ines, Neven, Patrick , Obi, Nadia , Offit, Kenneth , Park‐Simon, Tjoung‐Won , Patel, Alpa V. , Phillips, Kelly‐Anne , Plaseska-Karanfilska, Dijana, Rack, Brigitte , Rhenius, Valerie , Sawyer, Elinor J. , Schmutzler, Rita K. , Schuetze, Sabine, Shah, Mitul , Smichkoska, Snezhana , Tollenaar, Rob A.�E.�M. , Tomlinson, Ian , Vachon, Celine M. , Veen, Elke M. van , Wang, Qin , Wendt, Camilla, Wildiers, Hans , Adank, Muriel A. , Hooning, Maartje J. , Eccles, Diana , Plaseska‐Karanfilska, Dijana , Eccles, Diana , Evans, D Gareth , García-Closas, Montserrat , Phillips, Kelly-Anne , Wildiers, Hans , Lindblom, Annika , Plaseska-Karanfilska, Dijana , Sawyer, Elinor J , Schreurs, Maartje A. C. , Anton‐Culver, Hoda , Augustinsson, Annelie , Behrens, Sabine , Bojesen, Stig E. , Brauch, Hiltrud , Broeks, Annegien , Buys, Saundra S. , Castelao, Jose E. , Chung, Wendy K. , Colonna, Sarah V. , Couch, Fergus J. , Cox, Angela , Cross, Simon S. , Czene, Kamila , Dennis, Joe , Devilee, Peter , Dörk, Thilo , Dunning, Alison M. , Dwek, Miriam , Eriksson, Mikael , Fehm, Tanja , Figueroa, Jonine D. , Gabrielson, Marike , Gago-Domínguez, Manuela , García-Sáenz, José Á. , Genkinger, Jeanine M. , Graßmann, Felix , Hartikainen, Jaana M. , Hopper, John L. , Houlston, Richard S. , Jakubowska, Anna , Jernström, Helena , John, Esther M. , Jones, Michael E. , Kurian, Allison W. , Lambrechts, Diether , Marchand, Loı̈c Le , Lubiński, Jan , Lux, Michael P. , Mulligan, Anna Marie , Muranen, Taru , Nevanlinna, Heli , Newman, William G. , Olshan, Andrew F. , Peterlongo, Paolo , Polley, Eric C. , Presneau, Nadège , Pylkäs, Katri , Radice, Paolo , Rashid, Muhammad Usman , Robson, Mark E. , Romero, Atocha , Saloustros, Emmanouil , Scott, Christopher, Southey, Melissa C. , Tapper, William , Teras, Lauren R. , Tomczyk, Katarzyna , Troester, Melissa A. , Vachon, Celine M. , Winqvist, Robert , Ziogas, Argyrios , Hall, Per N , Pharoah, Paul D.P. , Hollestelle, Antoinette , Schmidt, Marjanka K.
No container title available | February 13, 2023 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers. We aimed to assess the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Analyses were based on 82,701 women diagnosed with invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations of treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR(95%CI): 0.66 (0.55–0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR(95%CI) :1.30 (1.09–1.56)]. In conclusion, systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk. (Main MS: 3201 words)
Cancer Risks Associated With GermlinePALB2Pathogenic Variants: An International Study of 524 Families
Yang, Xin , Doroszuk, Alicja, Schneider, Sandra , Allen, Jamie , Decker, Brennan , Redman, James , Scarth, James A. , Plaskocinska, Inga, Luccarini, Craig , Shah, Mitul , Pooley, Karen A. , Dorling, Leila , Lee, Andrew , Adank, Muriel A. , Aittomäki, Kristiina, Andrulis, Irene L. , Ang, Peter , Bernstein, Jonine L. , Bobolis, Kristie, Borg, Åke , Blomqvist, Carl , Claes, Kathleen , Cuggia, Adeline , Culver, Julie O. , Damiola, Francesca , Pauw, Antoine De , Dolinsky, Jill S. , Engel, Christoph , Evans, D. Gareth , Goode, Ellen L. , Gruber, Stephen B., Hahnen, Eric , Hake, Christopher R., Heikkinen, Tuomas , Hurley, Judith , Janavičius, Ramūnas , Kleibl, Zdeněk , Kleiblová, Petra , Konstantopoulou, Irene , Kvist, Anders , LaDuca, Holly , Lee, Ann S. G. , Lesueur, Fabienne , Mannermaa, Arto, Manoukian, Siranoush , McFarland, Rachel, McKinnon, Wendy, Meindl, Alfons , Metcalfe, Kelly , Taib, Nur Aishah Mohd , Moilanen, Jukka S. , Nathanson, Katherine L. , Ng, Pei Sze , Nguyen‐Dumont, Tú , Nielsen, Sarah M. , Obermair, Florian , Offit, Kenneth, Olopade, Olufunmilayo I. , Ottini, Laura , Penkert, Judith , Pylkäs, Katri , Ramus, Susan J. , Rudaitis, Vilius , Side, Lucy, Silva‐Smith, Rachel , Silvestri, Valentina , Skytte, Anne‐Bine , Slavin, Thomas, Soukupová, Jana , Trainer, Alison H., Unzeitig, Gary, Usha, Lydia , Hansen, Thomas van Overeem , Whitworth, James , Wood, Marie , Yip, Cheng Har , Yoon, Sook‐Yee , Yussuf, Amal , Zogopoulos, George , Goldgar, David E. , Chenevix‐Trench, Georgia , George, Sophia , Houdayer, Claude , James, Paul A. , El-Haffaf, Zaki, Ehrencrona, Hans , Janatová, Markéta , Peterlongo, Paolo , Nevanlinna, Heli, Schmutzler, Rita K., Teo, Soo‐Hwang , Weitzel, Jeffrey N. , Elliott, Aaron , Winqvist, Robert , Easton, Douglas F. , Antoniou, Antonis C. , Houdayer, Claude , James, Paul , Lesueur, Fabienne , Peterlongo, Paolo , Ramus, Susan J , Teo, Soo H , Weitzel, Jeffrey N , Claes, Kathleen B M , Ehrencrona, Hans , Evans, D Gareth , Konstantopoulou, Irene , Olopade, Olufunmilayo I , Silvestri, Valentina , Nathanson, Katherine L , Engel, Christoph , Nguyen-Dumont, Tu , Chenevix-Trench, Georgia , Ottini, Laura , Metcalfe, Kelly A , Pylkäs, Katri , Janatova, Marketa , Soukupova, Jana , Hansen, Thomas van Overeem , Kleibl, Zdenek , Manoukian, Siranoush , Mohd Taib, Nur Aishah , Decker, Brennan , Leslie, Goska , Dunning, Alison M. , Adlard, Julian , Barwell, Julian , CONCANNON, PATRICK J. , Dı́ez, Orland , Domchek, Susan M. , Fostira, Florentia , Garber, Judy E. , Golmard, Lisa , Maher, Eamonn R. , Mannermaa, Arto, Meindl, Alfons , Neuhausen, Susan L. , Radice, Paolo , Slavin, Thomas P. , Tondini, Carlo Alberto , Hopper, John L. , Pharoah, Paul D.P. , Balmañà, Judith , El-Haffaf, Zaki, Nevanlinna, Heli , Robson, Mark E. , Pal, Tuya , Couch, Fergus J. , Southey, Melissa C. , Foulkes, William D. , Tischkowitz, Marc D.
Journal of Clinical Oncology | December 16, 2019 | Volume: 38 | Issue: 7 | Pages: 674-685
PURPOSETo estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized.METHODSWe analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes.RESULTSWe found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10−76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10−3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10−3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 × 10−2). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age ( P for trend = 2.0 × 10−3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies ( P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer.CONCLUSIONThese results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.
Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study
Qian, Frank , Wang, Shengfeng , McGuffog, Lesley, Barrowdale, Daniel , Oosterwijk, Jan C., Evans, D. Gareth , Engel, Christoph , Kast, Karin, Aalfs, Cora M. , Adank, Muriel A. , Agnarsson, Bjarni A. , Aittomäki, Kristiina, Alducci, Elisa, Andrulis, Irene L. , Ausems, Margreet G.E.M. , Azzollini, Jacopo , Barouk-Simonet, Emmanuelle, Belotti, Muriel, Benı́tez, Javier , Berger, Andreas, Borg, Åke , Bradbury, Angela R. , Brunet, Joan , Caldés, Trinidad , Caputo, Sandrine M. , Chiquette, Jocelyne , Collée, J. Margriet, Coupier, Isabelle, Daly, Mary B., Davidson, Rosemarie, Donaldson, Alan, Dorfling, Cecilia M., Eeles, Rosalind A. , Feliubadaló, Lídia , Foretová, Lenka , Fowler, Jeffrey M., Friedman, Eitan , Frost, Debra, Ganz, Patricia A. , García‐Barberán, Vanesa , Glendon, Gord , Gómez, E. , Hahnen, Eric , Hamann, Ute, Henderson, Alex, Hendricks, Carolyn B., Hulick, Peter J. , Imyanitov, Evgeny N., Izatt, Louise , Jakubowska, Anna , Kaczmarek, Katarzyna, Kang, Eunyoung , Kets, Carolien M., Kim, Sung-Won, Kwong, Ava , Laitman, Yael , Lasset, Christine, Lee, Min Hyuk , Lee, Jong Won, Lee, Jihyoun , Lester, Jenny, Lesueur, Fabienne , Loud, Jennifer T. , Mebirouk, Noura, Meijers‐Heijboer, Hanne , Meindl, Alfons , Montagna, Marco , Mooij, Thea M. , Mouret‐Fourme, Emmanuelle, Nathanson, Katherine L. , Niederacher, Dieter , Offit, Kenneth, Oláh, Edith , Ong, Kai-Ren, Ottini, Laura , Park, Sue K. , Peterlongo, Paolo , Pfeiler, Georg , Phelan, Catherine M., Poppe, Bruce , Pradhan, Nisha , Radice, Paolo , Ramus, Susan J. , Rantala, Johanna, Rodriguez, Gustavo C. , Schmutzler, Rita K., Selkirk, Christina G. , Shah, Payal D. , Simard, Jacques , Sutter, Christian , Tan, Yen Y. , Teixeira, R , Teo, Soo‐Hwang , Terry, Mary Beth , Thomassen, Mads , Toland, Amanda Ewart, Tucker, Kathy , Engelen, Klaartje van , Rensburg, Elizabeth J. van , Wang‐Gohrke, Shan , Wappenschmidt, Barbara , Weitzel, Jeffrey N. , Collaborators, GEMO Study, HEBON, EMBRACE, Greene, Mark H. , Rookus, Matti A. , Easton, Douglas F. , Chenevix‐Trench, Georgia , Antoniou, Antonis C. , Goldgar, David E., Olopade, Olufunmilayo I. , Huo, Dezheng , Durocher, Francine , Teixeira, Manuel R. , Mitchell, Jonathan A. , Białkowska, Katarzyna , Hulick, Peter J , Lesueur, Fabienne , Peterlongo, Paolo , Ramus, Susan J , Teixeira, Manuel R , Teo, Soo H , van Rensburg, Elizabeth J , Radice, Paolo , Weitzel, Jeffrey N , Azzollini, Jacopo , Brunet, Joan , Eeles, Rosalind A , Evans, D Gareth , Olopade, Olufunmilayo I , Jakubowska, Anna , Nathanson, Katherine L , Barrowdale, Daniel , Benitez, Javier , Engel, Christoph , Montagna, Marco , Simard, Jacques , Chenevix-Trench, Georgia , Ottini, Laura , Mitchell, Jonathan S. , Leslie, Goska , Chung, Wendy K. , Adlard, Julian , Arun, Banu , Barwell, Julian , Borg, Åke , Buys, Saundra S. , Caligo, Maria A. , Campbell, Ian , Claes, Kathleen , Couch, Fergus J. , Dı́ez, Orland , Domchek, Susan M. , Garber, Judy E. , Godwin, Andrew K. , Gronwald, Jacek , Hopper, John L. , Isaacs, Claudine , Izquierdo, Á. , Karlan, Beth Y. , Kim, Sung-Won , Lasset, Christine , Lubiński, Jan , Meindl, Alfons , Miller, Austin , Morrison, Patrick J. , Neuhausen, Susan L. , Nevanlinna, Heli , Nielsen, Finn Cilius , Nussbaum, Robert L. , Robson, Mark E. , Singer, Christian F. , Giles, Graham G , Stoppa‐Lyonnet, Dominique , Tischkowitz, Marc D. , Toland, Amanda Ewart , Tung, Nadine , Asperen, Christi J. van , Yannoukakos, Drakoulis , Collaborators, GEMO Study, HEBON, EMBRACE, Rebbeck, Timothy R. , Feliubadaló, Lidia , Gómez-García, Encarna B , Terry, Mary Beth , Kwong, Ava
JNCI: Journal of the National Cancer Institute | July 3, 2018 | Volume: 111 | Issue: 4 | Pages: 350-364
The BRCA1 c. 5096G>A p.Arg1699Gln (R1699Q) intermediate risk variant: breast and ovarian cancer risk estimation and recommendations for clinical management from the ENIGMA consortium
Moghadasi, Setareh , Vreeswijk, Maaike P.G. , Janssen, Linda AM, Borg, Åke , Ehrencrona, Hans , Paulsson-Karlsson, Ylva, Wappenschmidt, Barbara , Engel, Christoph , Gehrig, Andrea, Hansen, Thomas van Overeem , Thomassen, Mads , Jensen, Uffe Birk , Kruse, Torben A., Ejlertsen, Bent , Gerdes, Anne‐Marie , Pedersen, Inge Søkilde , Caputo, Sandrine M. , Couch, Fergus J., Hallberg, Emily J., Ouweland, Ans MW van den, Collée, Margriet J., Teugels, Erik , Adank, Muriel A. , Luijt, Rob B. van der , Mensenkamp, Arjen R. , Oosterwijk, Jan C., Blok, Marinus J. , Janin, Nicolas, Claes, Kathleen , Tucker, Kathy , Viassolo, Valeria , Eccles, Diana , Devilee, Peter , Asperen, Christi J. van , Goldgar, David E., Gómez, E. , Meeks, Huong , Janssen, Linda A.M., Arnold, Norbert , Collée, Margriet , Toland, Amanda Ewart , Spurdle, Amanda B. , Eccles, Diana , Vreeswijk, Maaike P G , Claes, Kathleen B M , Ehrencrona, Hans , van der Luijt, Rob B , Engel, Christoph , van Asperen, Christi J , Gómez-García, Encarna B , Hansen, Thomas van Overeem , Devilee, Peter
Journal of Medical Genetics | May 11, 2017 | Volume: 55 | Issue: 1 | Pages: 15-20
Background We previously showed that the BRCA1 variant c.5096G>A p.Arg1699Gln (R1699Q) was associated with an intermediate risk of breast cancer (BC) and ovarian cancer (OC). This study aimed to assess these cancer risks for R1699Q carriers in a larger cohort, including follow-up of previously studied families, to further define cancer risks and to propose adjusted clinical management of female BRCA1*R1699Q carriers. Methods Data were collected from 129 BRCA1*R1699Q families ascertained internationally by ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) consortium members. A modified segregation analysis was used to calculate BC and OC risks. Relative risks were calculated under both monogenic model and major gene plus polygenic model assumptions. Results In this cohort the cumulative risk of BC and OC by age 70 years was 20% and 6%, respectively. The relative risk for developing cancer was higher when using a model that included the effects of both the R1699Q variant and a residual polygenic component compared with monogenic model (for BC 3.67 vs 2.83, and for OC 6.41 vs 5.83). Conclusion Our results confirm that BRCA1*R1699Q confers an intermediate risk for BC and OC. Breast surveillance for female carriers based on mammogram annually from age 40 is advised. Bilateral salpingo-oophorectomy should be considered based on family history.
Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations
Fehringer, Gordon , Kraft, Peter , Eeles, Rosalind A. , Chatterjee, Nilanjan , Schumacher, Fredrick R. , Schildkraut, Joellen M. , Lindström, Sara , Brennan, Paul , Bickeböller, Heike , Houlston, Richard S. , Landi, Maria Teresa , Caporaso, Neil E. , Risch, Angela , Olama, Ali Amin Al , Berndt, Sonja I. , Giovannucci, Edward L. , Grönberg, Henrik , Muir, Kenneth , Stampfer, Meir J. , Stevens, Victoria L. , Goode, Ellen L. , Reid, Brett M. , Brenner, Hermann , Chang‐Claude, Jenny , Kocarnik, Jonathan K., Slattery, Martha L. , Adank, Muriel A. , Ahsan, Habibul , Aittomäki, Kristiina, Baglietto, Laura , Blomquist, Carl, Canzian, Federico , Eliassen, A. Heather , Figueroa, Jonine D. , Flesch‐Janys, Dieter, Fletcher, Olivia , García‐Closas, Montserrat , Gaudet, Mia M. , Johnson, Nichola , Hazra, Aditi , Hein, Rebecca, Hofman, Albert , Irwanto, Astrid , Johansson, Mattias , Lichtner, Peter , Liu, Jianjun , Lund, Eiliv , Makalic, Enes , Meindl, Alfons , Müller‐Myhsok, Bertram , Muranen, Taru , Peeters, Petra H., Peto, Julian, Prentice, Ross L. , Sánchez, María‐José , Schmutzler, Rita K. , Southey, Melissa C. , Travis, Ruth C. , Turnbull, Clare , Uitterlinden, André G. , Wang, Zhaoming , Whittemore, Alice S. , Yang, Xiaohong R. , Zheng, Wei , Buchanan, Daniel D. , Casey, Graham , Conti, David V. , Edlund, Christopher K., Gallinger, Steven , Haile, Robert W. , Jenkins, Mark A. , Li, Li , Lindor, Noralene M., Schmit, Stephanie L. , Thibodeau, Stephen N. , Woods, Michael O. , Rafnar, Þórunn , Guðmundsson, Jūlı́us, Stacey, Simon , Stefánsson, Kāri , Sulem, Patrick , Chen, Y. Ann , Wei, Yongyue , Shen, Hongbing , Hu, Zhibin , Obeidat, Ma’en , Nickle, David C. , Timens, Wim , Freedman, Matthew L. , Seminara, Daniela, Gong, Jian , Peters, Ulrike , Gruber, Stephen B. , Sellers, Thomas A. , Easton, Douglas F. , Hunter, David J. , Haiman, Christopher A. , Henderson, Brian E., Hung, Rayjean J., Batra, Jyotsna , Hung, Rayjean J. , Pharoah, Paul D.P. , Kote‐Jarai, Zsofia , Ma, Jing , Wiklund, Fredrik E. , Willett, Walter C. , Permuth, Jennifer B. , Risch, Harvey A. , Bezieau, Stéphane , Chan, Andrew T. , Hudson, Thomas J , Newcomb, Polly A. , Schoen, Robert E. , White, Emily E. , Czene, Kamila , dos‐Santos‐Silva, Isabel , Hall, Per N , Hopper, John L. , Kaaks, Rudolf , Kibriya, Muhammad Ghulam , Meindl, Alfons , Nevanlinna, Heli , Rahman, Nazneen , Schmidt, Daniel F. , Tamimi, Rulla M. , Marchand, Loı̈c Le , Tyrer, Jonathan P. , Christiani, David C. , Shu, Xiao‐Ou , Shiraishi, Kouya , Takahashi, Atsushi , Bossé, Yohan , Li, Qiyuan , Chanock, Stephen Jacob , Amos, Christopher I. , Hung, Rayjean J., Buchanan, Daniel D , Houlston, Richard S , Eeles, Rosalind A , Southey, Melissa C , Jenkins, Mark A , Canzian, Federico , Hung, Rayjean J , Muir, Kenneth , Travis, Ruth C , Haile, Robert W , Wang, Zhaoming , Brenner, Hermann , Muranen, Taru A , García-Closas, Montserrat , Makalic, Enes , Kraft, Peter , Zheng, Wei , Figueroa, Jonine D , Eliassen, A Heather , Conti, David V , Batra, Jyotsna , Johansson, Mattias , Baglietto, Laura , Fletcher, Olivia , Sánchez, Maria-Jose , Risch, Angela , Bickeböller, Heike , Shen, Hongbing , Timens, Wim , Liu, Jing
Cancer Research | April 21, 2016 | Volume: 76 | Issue: 17 | Pages: 5103-5114
Abstract Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103–14. ©2016 AACR.
Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk
Lin, Wei‐Yu , Camp, Nicola J. , Ghoussaini, Maya , Beesley, Jonathan, Michailidou, Kyriaki , Hopper, John L. , Apicella, Carmel, Southey, Melissa C. , Stone, Jennifer , Schmidt, Marjanka K. , Veer, Laura J. van’t , Muir, Kenneth , Lophatananon, Artitaya, Stewart‐Brown, Sarah , Siriwanarangsan, Pornthep, Fasching, Peter A. , Haeberle, Lothar, Ekici, Arif B. , Beckmann, Matthias W. , Peto, Julian, dos‐Santos‐Silva, Isabel , Fletcher, Olivia , Johnson, Nichola , Bolla, Manjeet K. , Wang, Qin, Sawyer, Elinor J. , Cheng, Timothy, Tomlinson, Ian , Kerin, Michael J. , Miller, Nicola, Surowy, Harald , Burwinkel, Barbara , Guénel, Pascal , Truong, Thérèse , Ménégaux, F. , Mulot, Claire , Bojesen, Stig E. , Nordestgaard, Børge G. , Nielsen, Sune F. , Flyger, Henrik, Benı́tez, Javier , Zamora, M. Pilar , Pérez, José Ignacio Arias , Menéndez, Primitiva, González‐Neira, Anna , Pita, Guillermo , Alonso, M. Rosario, Álvarez, Núria, Herrero, Daniel, Brenner, Hermann , Dieffenbach, Aida Karina, Stegmaier, Christa, Meindl, Alfons , Lichtner, Peter , Schmutzler, Rita K., Müller‐Myhsok, Bertram , Brauch, Hiltrud , Brüning, Thomas , Ko, Yon‐Dschun, Network, The GENICA, Tessier, Daniel C., Vincent, Daniel , Bacot, François, Nevanlinna, Heli , Aittomäki, Kristiina, Blomqvist, Carl , Khan, Sofia , Matsuo, Keitaro , Iwata, Hiroji, Horio, Akiyo, Bogdanova, Natalia , Antonenkova, Natalia, Dörk, Thilo , Lindblom, Annika , Margolin, Sara , Mannermaa, Arto, Kataja, Vesa , Kosma, Veli‐Matti, Hartikainen, Jaana M. , Investigators, kConFab, Group, Australian Ovarian Cancer Study, Wu, Anna H. , Tseng, Chiu-Chen , Neven, Patrick , Wauters, Els , Wildiers, Hans , Lambrechts, Diether , Chang‐Claude, Jenny , Flesch‐Janys, Dieter, Radice, Paolo , Peterlongo, Paolo , Manoukian, Siranoush , Couch, Fergus J. , Vachon, Celine M. , Purrington, Kristen S. , Giles, Graham G. , McLean, Catriona , Haiman, Christopher A., Henderson, Brian E., Schumacher, Fredrick R. , Simard, Jacques , Goldberg, Mark S. , Dumont, Martine , Teo, Soo‐Hwang , Yip, Cheng Har , Vithana, Eranga N. , Kristensen, Vessela N. , Deming-Halverson, Sandra, Shrubsole, Martha J. , Long, Jirong , Winqvist, Robert , Pylkäs, Katri , Jukkola‐Vuorinen, Arja , Kauppila, Saila , Andrulis, Irene L. , Knight, Julia A. , Glendon, Gord, Tchatchou, Sandrine, Devilee, Peter , Tollenaar, Robert A.E.M., Seynaeve, Caroline, García‐Closas, Montserrat , Figueroa, Jonine D. , Lissowska, Jolanta , Brinton, Louise A. , Czene, Kamila , Darabi, Hatef, Eriksson, Mikael , Brand, Judith S. , Hooning, Maartje J. , Hollestelle, Antoinette , Ouweland, Ans M.W. van den, Jager, Agnes , Li, Jingmei , Liu, Jianjun , Humphreys, Keith , Shu, Xiao‐Ou , Lu, Wei , Gao, Yu‐Tang , Cai, Hui , Cross, Simon S. , Reed, Malcolm , Blot, William J. , Signorello, Lisa B., Cai, Qiuyin, Perkins, Barbara, Shah, Mitul, Blows, Fiona M., Kang, Daehee , Yoo, Keun-Young, Noh, Dong‐Young , Hartman, Mikael , Miao, Hui , Chia, Kee Seng , Putti, Thomas Choudary , Hamann, Ute , Luccarini, Craig , Baynes, Caroline, Maranian, Mel, Healey, Catherine S., Jakubowska, Anna , Lubiński, Jan , Jaworska–Bieniek, Katarzyna, Durda, Katarzyna, Sangrajrang, Suleeporn , Gaborieau, Valérie , Brennan, Paul , McKay, James , Slager, Susan, Yannoukakos, Drakoulis , Hsiung, Chia‐Ni , Wu, Pei‐Ei , Ding, Shian-ling, Ashworth, Alan , Jones, Michael E. , Orr, Nick , Swerdlow, Anthony J. , Makalic, Enes , Bui, Minh , Hunter, David J. , Hein, Rebecca, Dahmen, Norbert, Beckmann, Lars , Aaltonen, Kirsimari, Muranen, Taru , Heikkinen, Tuomas , Irwanto, Astrid , Rahman, Nazneen , Turnbull, Clare , Study, The Breast and Ovarian Cancer Susceptibility (BOCS), Waisfisz, Quinten , Meijers‐Heijboer, Hanne , Adank, Muriel A. , Luijt, Rob B. van der , Chenevix‐Trench, Georgia , Dunning, Alison M. , Easton, Douglas F. , Cox, Angela , Durocher, Francine , Zheng, Wei , Thorne, Heather , Lambrechts, Diether , Vachon, Celine, Broeks, Annegien , Rutgers, Emiel J. , Wang, Qin, Dennis, Joe , Marmé, Frederik , Anton‐Culver, Hoda , Arndt, Volker , Meindl, Alfons , Network, The GENICA, Ito, Hidemi , Iwata, Hiroji , Mannermaa, Arto , Investigators, kConFab, Group, Australian Ovarian Cancer Study, Berg, David Van Den , Stram, Daniel O. , Rudolph, Anja , Seibold, Petra , Bonanni, Bernardo , Couch, Fergus J. , Wang, Xianshu , Vachon, Celine M. , Milne, Roger L. , Marchand, Loı̈c Le , Labrèche, France , Rudolph, Anja , Zheng, Wei , Asperen, Christi J. van , Eriksson, Mikael , Hooning, Maartje J. , Pharoah, Paul D.P. , Ahmed, Shahana , Toland, Amanda Ewart , Shen, Chen‐Yang , Tsimiklis, Helen , Schmidt, Daniel Frederick , Bui, Minh , Chanock, Stephen Jacob , Study, The Breast and Ovarian Cancer Susceptibility (BOCS), Hall, Per N , Nevanlinna, H , Dörk, Thilo , Lambrechts, Diether , Giles, Graham G , Peterlongo, Paolo , Teo, Soo H , Shrubsole, Martha J , Swerdlow, Anthony J , Radice, Paolo , Lissowska, Jolanta , Southey, Melissa C , van der Luijt, Rob B , Muir, Kenneth , Shu, Xiao-Ou , Matsuo, Keitaro , Dunning, Alison M , Jakubowska, Anna , Jones, Michael E , Lambrechts, Diether , Brenner, Hermann , Cox, Angela , Guénel, Pascal , Hartman, Mikael , Li, Jingmei , Muranen, Taru A , García-Closas, Montserrat , Schmidt, Marjanka K , Makalic, Enes , Ekici, Arif B , Michailidou, Kyriaki , Hartikainen, Jaana M , Bogdanova, Natalia V , Benitez, Javier , Simard, Jacques , Chenevix-Trench, Georgia , Zheng, Wei , Figueroa, Jonine D , Czene, Kamila , Stone, Jennifer , Pylkäs, Katri , Yannoukakos, Drakoulis , Devilee, Peter , Manoukian, Siranoush , Lubinski, Jan , Fletcher, Olivia , Bojesen, Stig E , Purrington, Kristen S , Truong, Therese , Wildiers, Hans , Mclean, Catriona , Brauch, Hiltrud , Lindblom, Annika , Sawyer, Elinor J , Orr, Nick , Liu, Jing , Kang, Daehee
Human Molecular Genetics | August 29, 2014 | Volume: 24 | Issue: 1 | Pages: 285-298