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Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants

PURPOSE To provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in BRCA1 and BRCA2 for effective cancer risk management. METHODS We used data from 3,184 BRCA1 and 2,157 BRCA2 families in the Consortium of Invest...

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Main Authors:	Li, Shuai, Silvestri, Valentina, Leslie, Goska, Rebbeck, Timothy R., Neuhausen, Susan L., Hopper, John L., Nielsen, Henriette Roed, Lee, Andrew, Yang, Xin, McGuffog, Lesley, Parsons, Michael T., Andrulis, Irene L., Arnold, Norbert, Belotti, Muriel, Borg, Ake, Buecher, Bruno, Buys, Saundra S., Caputo, Sandrine M., Chung, Wendy K., Colas, Chrystelle, Colonna, Sarah, Cook, Jackie, Daly, Mary B., de la Hoya, Miguel, de Pauw, Antoine, Delhomelle, Helene, Eason, Jacqueline, Engel, Christoph, Evans, D. Gareth, Faust, Ulrike, Fehm, Tanja N., Fostira, Florentia, Fountzilas, George, Frone, Megan, Garcia-Barberan, Vanesa, Garre, Pilar, Gauthier-Villars, Marion, Gehrig, Andrea, Glendon, Gord, Goldgar, David E., Golmard, Lisa, Greene, Mark H., Hahnen, Eric, Hamann, Ute, Hanson, Helen, Hassan, Tiara, Hentschel, Julia, Horvath, Judit, Izatt, Louise, Janavicius, Ramunas, Jiao, Yue, John, Esther M., Karlan, Beth Y., Kim, Sung-Won, Konstantopoulou, Irene, Kwong, Ava, Lauge, Anthony, Lee, Jong Won, Lesueur, Fabienne, Mebirouk, Noura, Meindl, Alfons, Mouret-Fourme, Emmanuelle, Musgrave, Hannah, Yie, Joanne Ngeow Yuen, Niederacher, Dieter, Park, Sue K., Pedersen, Inge Sokilde, Ramser, Juliane, Ramus, Susan J., Rantala, Johanna, Rashid, Muhammad U., Reichl, Florian, Ritter, Julia, Rump, Andreas, Santamarina, Marta, Saule, Claire, Schmidt, Gunnar, Schmutzler, Rita K., Senter, Leigha, Shariff, Saba, Singer, Christian F., Southey, Melissa C., Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen, Teo, Soo Hwang, Terry, Mary Beth, Thomassen, Mads, Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Vega, Ana, Wagner, Sebastian A., Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weber, Bernhard H. F., Yannoukakos, Drakoulis, Spurdle, Amanda B., Easton, Douglas F., Chenevix-Trench, Georgia, Ottini, Laura, Antoniou, Antonis C.
Format:	Article
Published:	Lippincott Williams & Wilkins 2022
Subjects:	RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Online Access:	http://eprints.um.edu.my/41729/ https://doi.org/10.1200/JCO.21.02112
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id	my.um.eprints.41729
record_format	eprints
institution	Universiti Malaya
building	UM Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Universiti Malaya
content_source	UM Research Repository
url_provider	http://eprints.um.edu.my/
topic	RC0254 Neoplasms. Tumors. Oncology (including Cancer)
spellingShingle	RC0254 Neoplasms. Tumors. Oncology (including Cancer) Li, Shuai Silvestri, Valentina Leslie, Goska Rebbeck, Timothy R. Neuhausen, Susan L. Hopper, John L. Nielsen, Henriette Roed Lee, Andrew Yang, Xin McGuffog, Lesley Parsons, Michael T. Andrulis, Irene L. Arnold, Norbert Belotti, Muriel Borg, Ake Buecher, Bruno Buys, Saundra S. Caputo, Sandrine M. Chung, Wendy K. Colas, Chrystelle Colonna, Sarah Cook, Jackie Daly, Mary B. de la Hoya, Miguel de Pauw, Antoine Delhomelle, Helene Eason, Jacqueline Engel, Christoph Evans, D. Gareth Faust, Ulrike Fehm, Tanja N. Fostira, Florentia Fountzilas, George Frone, Megan Garcia-Barberan, Vanesa Garre, Pilar Gauthier-Villars, Marion Gehrig, Andrea Glendon, Gord Goldgar, David E. Golmard, Lisa Greene, Mark H. Hahnen, Eric Hamann, Ute Hanson, Helen Hassan, Tiara Hentschel, Julia Horvath, Judit Izatt, Louise Janavicius, Ramunas Jiao, Yue John, Esther M. Karlan, Beth Y. Kim, Sung-Won Konstantopoulou, Irene Kwong, Ava Lauge, Anthony Lee, Jong Won Lesueur, Fabienne Mebirouk, Noura Meindl, Alfons Mouret-Fourme, Emmanuelle Musgrave, Hannah Yie, Joanne Ngeow Yuen Niederacher, Dieter Park, Sue K. Pedersen, Inge Sokilde Ramser, Juliane Ramus, Susan J. Rantala, Johanna Rashid, Muhammad U. Reichl, Florian Ritter, Julia Rump, Andreas Santamarina, Marta Saule, Claire Schmidt, Gunnar Schmutzler, Rita K. Senter, Leigha Shariff, Saba Singer, Christian F. Southey, Melissa C. Stoppa-Lyonnet, Dominique Sutter, Christian Tan, Yen Teo, Soo Hwang Terry, Mary Beth Thomassen, Mads Tischkowitz, Marc Toland, Amanda E. Torres, Diana Vega, Ana Wagner, Sebastian A. Wang-Gohrke, Shan Wappenschmidt, Barbara Weber, Bernhard H. F. Yannoukakos, Drakoulis Spurdle, Amanda B. Easton, Douglas F. Chenevix-Trench, Georgia Ottini, Laura Antoniou, Antonis C. Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants
description	PURPOSE To provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in BRCA1 and BRCA2 for effective cancer risk management. METHODS We used data from 3,184 BRCA1 and 2,157 BRCA2 families in the Consortium of Investigators of Modifiers of BRCA1/2 to estimate age-specific relative (RR) and absolute risks for 22 first primary cancer types adjusting for family ascertainment. RESULTS BRCA1 PVs were associated with risks of male breast (RR = 4.30; 95% CI, 1.09 to 16.96), pancreatic (RR = 2.36; 95% CI, 1.51 to 3.68), and stomach (RR = 2.17; 95% CI, 1.25 to 3.77) cancers. Associations with colorectal and gallbladder cancers were also suggested. BRCA2 PVs were associated with risks of male breast (RR = 44.0; 95% CI, 21.3 to 90.9), stomach (RR = 3.69; 95% CI, 2.40 to 5.67), pancreatic (RR = 3.34; 95% CI, 2.21 to 5.06), and prostate (RR = 2.22; 95% CI, 1.63 to 3.03) cancers. The stomach cancer RR was higher for females than males (6.89 v 2.76; P = .04). The absolute risks to age 80 years ranged from 0.4% for male breast cancer to approximately 2.5% for pancreatic cancer for BRCA1 carriers and from approximately 2.5% for pancreatic cancer to 27% for prostate cancer for BRCA2 carriers. CONCLUSION In addition to female breast and ovarian cancers, BRCA1 and BRCA2 PVs are associated with increased risks of male breast, pancreatic, stomach, and prostate (only BRCA2 PVs) cancers, but not with the risks of other previously suggested cancers. The estimated age-specific risks will refine cancer risk management in men and women with BRCA1/2 PVs.
format	Article
author	Li, Shuai Silvestri, Valentina Leslie, Goska Rebbeck, Timothy R. Neuhausen, Susan L. Hopper, John L. Nielsen, Henriette Roed Lee, Andrew Yang, Xin McGuffog, Lesley Parsons, Michael T. Andrulis, Irene L. Arnold, Norbert Belotti, Muriel Borg, Ake Buecher, Bruno Buys, Saundra S. Caputo, Sandrine M. Chung, Wendy K. Colas, Chrystelle Colonna, Sarah Cook, Jackie Daly, Mary B. de la Hoya, Miguel de Pauw, Antoine Delhomelle, Helene Eason, Jacqueline Engel, Christoph Evans, D. Gareth Faust, Ulrike Fehm, Tanja N. Fostira, Florentia Fountzilas, George Frone, Megan Garcia-Barberan, Vanesa Garre, Pilar Gauthier-Villars, Marion Gehrig, Andrea Glendon, Gord Goldgar, David E. Golmard, Lisa Greene, Mark H. Hahnen, Eric Hamann, Ute Hanson, Helen Hassan, Tiara Hentschel, Julia Horvath, Judit Izatt, Louise Janavicius, Ramunas Jiao, Yue John, Esther M. Karlan, Beth Y. Kim, Sung-Won Konstantopoulou, Irene Kwong, Ava Lauge, Anthony Lee, Jong Won Lesueur, Fabienne Mebirouk, Noura Meindl, Alfons Mouret-Fourme, Emmanuelle Musgrave, Hannah Yie, Joanne Ngeow Yuen Niederacher, Dieter Park, Sue K. Pedersen, Inge Sokilde Ramser, Juliane Ramus, Susan J. Rantala, Johanna Rashid, Muhammad U. Reichl, Florian Ritter, Julia Rump, Andreas Santamarina, Marta Saule, Claire Schmidt, Gunnar Schmutzler, Rita K. Senter, Leigha Shariff, Saba Singer, Christian F. Southey, Melissa C. Stoppa-Lyonnet, Dominique Sutter, Christian Tan, Yen Teo, Soo Hwang Terry, Mary Beth Thomassen, Mads Tischkowitz, Marc Toland, Amanda E. Torres, Diana Vega, Ana Wagner, Sebastian A. Wang-Gohrke, Shan Wappenschmidt, Barbara Weber, Bernhard H. F. Yannoukakos, Drakoulis Spurdle, Amanda B. Easton, Douglas F. Chenevix-Trench, Georgia Ottini, Laura Antoniou, Antonis C.
author_facet	Li, Shuai Silvestri, Valentina Leslie, Goska Rebbeck, Timothy R. Neuhausen, Susan L. Hopper, John L. Nielsen, Henriette Roed Lee, Andrew Yang, Xin McGuffog, Lesley Parsons, Michael T. Andrulis, Irene L. Arnold, Norbert Belotti, Muriel Borg, Ake Buecher, Bruno Buys, Saundra S. Caputo, Sandrine M. Chung, Wendy K. Colas, Chrystelle Colonna, Sarah Cook, Jackie Daly, Mary B. de la Hoya, Miguel de Pauw, Antoine Delhomelle, Helene Eason, Jacqueline Engel, Christoph Evans, D. Gareth Faust, Ulrike Fehm, Tanja N. Fostira, Florentia Fountzilas, George Frone, Megan Garcia-Barberan, Vanesa Garre, Pilar Gauthier-Villars, Marion Gehrig, Andrea Glendon, Gord Goldgar, David E. Golmard, Lisa Greene, Mark H. Hahnen, Eric Hamann, Ute Hanson, Helen Hassan, Tiara Hentschel, Julia Horvath, Judit Izatt, Louise Janavicius, Ramunas Jiao, Yue John, Esther M. Karlan, Beth Y. Kim, Sung-Won Konstantopoulou, Irene Kwong, Ava Lauge, Anthony Lee, Jong Won Lesueur, Fabienne Mebirouk, Noura Meindl, Alfons Mouret-Fourme, Emmanuelle Musgrave, Hannah Yie, Joanne Ngeow Yuen Niederacher, Dieter Park, Sue K. Pedersen, Inge Sokilde Ramser, Juliane Ramus, Susan J. Rantala, Johanna Rashid, Muhammad U. Reichl, Florian Ritter, Julia Rump, Andreas Santamarina, Marta Saule, Claire Schmidt, Gunnar Schmutzler, Rita K. Senter, Leigha Shariff, Saba Singer, Christian F. Southey, Melissa C. Stoppa-Lyonnet, Dominique Sutter, Christian Tan, Yen Teo, Soo Hwang Terry, Mary Beth Thomassen, Mads Tischkowitz, Marc Toland, Amanda E. Torres, Diana Vega, Ana Wagner, Sebastian A. Wang-Gohrke, Shan Wappenschmidt, Barbara Weber, Bernhard H. F. Yannoukakos, Drakoulis Spurdle, Amanda B. Easton, Douglas F. Chenevix-Trench, Georgia Ottini, Laura Antoniou, Antonis C.
author_sort	Li, Shuai
title	Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants
title_short	Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants
title_full	Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants
title_fullStr	Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants
title_full_unstemmed	Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants
title_sort	cancer risks associated with brca1 and brca2 pathogenic variants
publisher	Lippincott Williams & Wilkins
publishDate	2022
url	http://eprints.um.edu.my/41729/ https://doi.org/10.1200/JCO.21.02112
_version_	1825160584489861120
spelling	my.um.eprints.417292025-01-17T07:10:47Z http://eprints.um.edu.my/41729/ Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants Li, Shuai Silvestri, Valentina Leslie, Goska Rebbeck, Timothy R. Neuhausen, Susan L. Hopper, John L. Nielsen, Henriette Roed Lee, Andrew Yang, Xin McGuffog, Lesley Parsons, Michael T. Andrulis, Irene L. Arnold, Norbert Belotti, Muriel Borg, Ake Buecher, Bruno Buys, Saundra S. Caputo, Sandrine M. Chung, Wendy K. Colas, Chrystelle Colonna, Sarah Cook, Jackie Daly, Mary B. de la Hoya, Miguel de Pauw, Antoine Delhomelle, Helene Eason, Jacqueline Engel, Christoph Evans, D. Gareth Faust, Ulrike Fehm, Tanja N. Fostira, Florentia Fountzilas, George Frone, Megan Garcia-Barberan, Vanesa Garre, Pilar Gauthier-Villars, Marion Gehrig, Andrea Glendon, Gord Goldgar, David E. Golmard, Lisa Greene, Mark H. Hahnen, Eric Hamann, Ute Hanson, Helen Hassan, Tiara Hentschel, Julia Horvath, Judit Izatt, Louise Janavicius, Ramunas Jiao, Yue John, Esther M. Karlan, Beth Y. Kim, Sung-Won Konstantopoulou, Irene Kwong, Ava Lauge, Anthony Lee, Jong Won Lesueur, Fabienne Mebirouk, Noura Meindl, Alfons Mouret-Fourme, Emmanuelle Musgrave, Hannah Yie, Joanne Ngeow Yuen Niederacher, Dieter Park, Sue K. Pedersen, Inge Sokilde Ramser, Juliane Ramus, Susan J. Rantala, Johanna Rashid, Muhammad U. Reichl, Florian Ritter, Julia Rump, Andreas Santamarina, Marta Saule, Claire Schmidt, Gunnar Schmutzler, Rita K. Senter, Leigha Shariff, Saba Singer, Christian F. Southey, Melissa C. Stoppa-Lyonnet, Dominique Sutter, Christian Tan, Yen Teo, Soo Hwang Terry, Mary Beth Thomassen, Mads Tischkowitz, Marc Toland, Amanda E. Torres, Diana Vega, Ana Wagner, Sebastian A. Wang-Gohrke, Shan Wappenschmidt, Barbara Weber, Bernhard H. F. Yannoukakos, Drakoulis Spurdle, Amanda B. Easton, Douglas F. Chenevix-Trench, Georgia Ottini, Laura Antoniou, Antonis C. RC0254 Neoplasms. Tumors. Oncology (including Cancer) PURPOSE To provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in BRCA1 and BRCA2 for effective cancer risk management. METHODS We used data from 3,184 BRCA1 and 2,157 BRCA2 families in the Consortium of Investigators of Modifiers of BRCA1/2 to estimate age-specific relative (RR) and absolute risks for 22 first primary cancer types adjusting for family ascertainment. RESULTS BRCA1 PVs were associated with risks of male breast (RR = 4.30; 95% CI, 1.09 to 16.96), pancreatic (RR = 2.36; 95% CI, 1.51 to 3.68), and stomach (RR = 2.17; 95% CI, 1.25 to 3.77) cancers. Associations with colorectal and gallbladder cancers were also suggested. BRCA2 PVs were associated with risks of male breast (RR = 44.0; 95% CI, 21.3 to 90.9), stomach (RR = 3.69; 95% CI, 2.40 to 5.67), pancreatic (RR = 3.34; 95% CI, 2.21 to 5.06), and prostate (RR = 2.22; 95% CI, 1.63 to 3.03) cancers. The stomach cancer RR was higher for females than males (6.89 v 2.76; P = .04). The absolute risks to age 80 years ranged from 0.4% for male breast cancer to approximately 2.5% for pancreatic cancer for BRCA1 carriers and from approximately 2.5% for pancreatic cancer to 27% for prostate cancer for BRCA2 carriers. CONCLUSION In addition to female breast and ovarian cancers, BRCA1 and BRCA2 PVs are associated with increased risks of male breast, pancreatic, stomach, and prostate (only BRCA2 PVs) cancers, but not with the risks of other previously suggested cancers. The estimated age-specific risks will refine cancer risk management in men and women with BRCA1/2 PVs. Lippincott Williams & Wilkins 2022-05 Article PeerReviewed Li, Shuai and Silvestri, Valentina and Leslie, Goska and Rebbeck, Timothy R. and Neuhausen, Susan L. and Hopper, John L. and Nielsen, Henriette Roed and Lee, Andrew and Yang, Xin and McGuffog, Lesley and Parsons, Michael T. and Andrulis, Irene L. and Arnold, Norbert and Belotti, Muriel and Borg, Ake and Buecher, Bruno and Buys, Saundra S. and Caputo, Sandrine M. and Chung, Wendy K. and Colas, Chrystelle and Colonna, Sarah and Cook, Jackie and Daly, Mary B. and de la Hoya, Miguel and de Pauw, Antoine and Delhomelle, Helene and Eason, Jacqueline and Engel, Christoph and Evans, D. Gareth and Faust, Ulrike and Fehm, Tanja N. and Fostira, Florentia and Fountzilas, George and Frone, Megan and Garcia-Barberan, Vanesa and Garre, Pilar and Gauthier-Villars, Marion and Gehrig, Andrea and Glendon, Gord and Goldgar, David E. and Golmard, Lisa and Greene, Mark H. and Hahnen, Eric and Hamann, Ute and Hanson, Helen and Hassan, Tiara and Hentschel, Julia and Horvath, Judit and Izatt, Louise and Janavicius, Ramunas and Jiao, Yue and John, Esther M. and Karlan, Beth Y. and Kim, Sung-Won and Konstantopoulou, Irene and Kwong, Ava and Lauge, Anthony and Lee, Jong Won and Lesueur, Fabienne and Mebirouk, Noura and Meindl, Alfons and Mouret-Fourme, Emmanuelle and Musgrave, Hannah and Yie, Joanne Ngeow Yuen and Niederacher, Dieter and Park, Sue K. and Pedersen, Inge Sokilde and Ramser, Juliane and Ramus, Susan J. and Rantala, Johanna and Rashid, Muhammad U. and Reichl, Florian and Ritter, Julia and Rump, Andreas and Santamarina, Marta and Saule, Claire and Schmidt, Gunnar and Schmutzler, Rita K. and Senter, Leigha and Shariff, Saba and Singer, Christian F. and Southey, Melissa C. and Stoppa-Lyonnet, Dominique and Sutter, Christian and Tan, Yen and Teo, Soo Hwang and Terry, Mary Beth and Thomassen, Mads and Tischkowitz, Marc and Toland, Amanda E. and Torres, Diana and Vega, Ana and Wagner, Sebastian A. and Wang-Gohrke, Shan and Wappenschmidt, Barbara and Weber, Bernhard H. F. and Yannoukakos, Drakoulis and Spurdle, Amanda B. and Easton, Douglas F. and Chenevix-Trench, Georgia and Ottini, Laura and Antoniou, Antonis C. (2022) Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants. Journal of Clinical Oncology, 40 (14). 1529+. ISSN 0732-183X, DOI https://doi.org/10.1200/JCO.21.02112 <https://doi.org/10.1200/JCO.21.02112>. https://doi.org/10.1200/JCO.21.02112 10.1200/JCO.21.02112
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Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants

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