Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants

被引：143

作者：

Li, Shuai ^{[1
,2
,3
]}

Silvestri, Valentina ^{[4
]}

Leslie, Goska ^{[2
]}

Rebbeck, Timothy R. ^{[5
,6
]}

Neuhausen, Susan L. ^{[7
]}

Hopper, John L. ^{[1
]}

Nielsen, Henriette Roed ^{[8
]}

Lee, Andrew ^{[2
]}

Yang, Xin ^{[2
]}

McGuffog, Lesley ^{[2
]}

Parsons, Michael T. ^{[9
]}

Andrulis, Irene L. ^{[10
,11
]}

Arnold, Norbert ^{[12
,13
]}

Belotti, Muriel ^{[14
,15
]}

Borg, Ake ^{[16
]}

Buecher, Bruno ^{[14
,15
]}

Buys, Saundra S. ^{[17
,18
]}

Caputo, Sandrine M. ^{[14
,15
]}

Chung, Wendy K. ^{[19
,20
]}

Colas, Chrystelle ^{[14
,15
]}

Colonna, Sarah, V ^{[17
,18
]}

Cook, Jackie ^{[21
]}

Daly, Mary B. ^{[22
]}

de la Hoya, Miguel ^{[23
]}

de Pauw, Antoine ^{[14
,15
]}

Delhomelle, Helene ^{[14
,15
]}

Eason, Jacqueline ^{[24
]}

Engel, Christoph ^{[25
]}

Evans, D. Gareth ^{[26
,27
]}

Faust, Ulrike ^{[28
]}

Fehm, Tanja N. ^{[29
]}

Fostira, Florentia ^{[30
]}

Fountzilas, George ^{[31
,32
]}

Frone, Megan ^{[33
]}

Garcia-Barberan, Vanesa ^{[23
]}

Garre, Pilar ^{[23
]}

Gauthier-Villars, Marion ^{[14
,15
]}

Gehrig, Andrea ^{[34
]}

Glendon, Gord ^{[10
]}

Goldgar, David E. ^{[35
]}

Golmard, Lisa ^{[14
,15
]}

Greene, Mark H. ^{[33
]}

Hahnen, Eric ^{[36
,37
,38
]}

Hamann, Ute ^{[39
]}

Hanson, Helen ^{[40
]}

Hassan, Tiara ^{[41
]}

Hentschel, Julia ^{[42
]}

Horvath, Judit ^{[43
]}

Izatt, Louise ^{[44
]}

Janavicius, Ramunas ^{[45
,46
]}

机构：

[1] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Parkville, Vic, Australia

[2] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England

[3] Monash Univ, Sch Clin Sci, Precis Med, Monash Hlth, Clayton, Vic, Australia

[4] Sapienza Univ Rome, Dept Mol Med, Rome, Italy

[5] Harvard TH Chan Sch Publ Hlth, Boston, MA USA

[6] Dana Farber Canc Inst, Boston, MA 02115 USA

[7] City Hope Natl Med Ctr, Dept Populat Sci, Beckman Res Inst, Duarte, CA USA

[8] Odense Univ Hosp, Dept Clin Genet, Odence, Denmark

[9] QIMR Berghofer Med Res Inst, Dept Genet & Computat Biol, Brisbane, Qld, Australia

[10] Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada

[11] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada

[12] Christian Albrechts Univ Kiel, Univ Hosp Schleswig Holstein, Dept Gynaecol & Obstet, Campus Kiel, Kiel, Germany

[13] Christian Albrechts Univ Kiel, Univ Hosp Schleswig Holstein, Inst Clin Mol Biol, Campus Kiel, Kiel, Germany

[14] Inst Curie, Serv Genet, Paris, France

[15] Paris Sci Lettres Res Univ, Paris, France

[16] Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, Lund, Sweden

[17] Univ Utah Hlth, Dept Med v, Salt Lake City, UT USA

[18] Univ Utah Hlth, Huntsman Canc Inst, Salt Lake City, UT USA

[19] Columbia Univ, Dept Pediat, New York, NY 10027 USA

[20] Columbia Univ, Dept Med, New York, NY USA

[21] Sheffield Childrens Hosp, Sheffield Clin Genet Serv, Sheffield, S Yorkshire, England

[22] Fox Chase Canc Ctr, Dept Clin Genet, 7701 Burholme Ave, Philadelphia, PA 19111 USA

[23] Hosp Clin San Carlos, IdISSC Inst Invest Sanitaria, Mol Oncol Lab, CIBERONC, Madrid, Spain

[24] Nottingham Univ Hosp NHS Trust, Nottingham Clin Genet Serv, Nottingham, England

[25] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany

[26] Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Biol Med & Hlth, Sch Biol Sci,Div Evolut & Genom Sci, Manchester, Lancs, England

[27] Manchester Univ NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester Ctr Genom Med, St Marys Hosp, Manchester, Lancs, England

[28] Univ Tubingen, Inst Med Genet & Appl Genom, Tubingen, Germany

[29] Heinrich Heine Univ Dusseldorf, Univ Hosp Dusseldorf, Dept Gynecol & Obstet, Dusseldorf, Germany

[30] Natl Ctr Sci Res Demokritos, Mol Diagnost Lab, INRASTES, Athens, Greece

[31] Aristotle Univ Thessaloniki, Sch Med, Thessaloniki, Greece

[32] German Oncol Ctr, Dept Med Oncol, Limassol, Cyprus

[33] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[34] Univ Wurzburg, Dept Human Genet, Wurzburg, Germany

[35] Univ Utah, Sch Med, Dept Dermatol, Huntsman Canc Inst, Salt Lake City, UT USA

[36] Univ Cologne, Fac Med, Ctr Familial Breast & Ovarian Canc, Cologne, Germany

[37] Univ Cologne, Univ Hosp Cologne, Cologne, Germany

[38] Univ Cologne, Fac Med, Ctr Integrated Oncol CIO, Cologne, Germany

[39] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany

[40] St George Hosp, Southwest Thames Reg Genet Serv, London, England

[41] Canc Res Malaysia, Breast Canc Res Programme, Subang Jaya, Selangor, Malaysia

[42] Univ Hosp Leipzig, Inst Human Genet, Leipzig, Germany

[43] Univ Munster, Inst Human Genet, Munster, Germany

[44] Guys & St Thomas NHS Fdn Trust, Clin Genet Dept, London, England

[45] Vilnius Univ, Fac Med, Inst Biomed Sci, Dept Human & Med Genet, Vilnius, Lithuania

[46] State Res Inst Ctr Innovat Med, Vilnius, Lithuania

[47] Inserm U900, Genet Epidemiol Canc Team, Paris, France

[48] Inst Curie, Paris, France

[49] Mines ParisTech, Fontainebleau, France

[50] Stanford Univ, Sch Med, Dept Epidemiol & Populat Hlth, Stanford, CA USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2022年 / 40卷 / 14期

基金：

加拿大健康研究院; 澳大利亚国家健康与医学研究理事会;

关键词：

ASCERTAINMENT SAMPLING PROBLEM; BREAST-CANCER; PROSTATE-CANCER; FAMILY-HISTORY; MUTATIONS; CARRIERS; OVARIAN; RESOLUTION;

D O I：

10.1200/JCO.21.02112

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：1529 / +

页数：14

共 50 条

[1] BRCA1 and BRCA2 cancer risks
Antoniou, Antonis C.
Pharoah, Paul D. P.
Easton, Douglas F.
Evans, D. Gareth
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (20) : 3312 - 3313
[2] Expansion of Cancer Risk Profile for BRCA1 and BRCA2 Pathogenic Variants
Momozawa, Yukihide
Sasai, Rumi
Usui, Yoshiaki
Shiraishi, Kouya
Iwasaki, Yusuke
Taniyama, Yukari
Parsons, Michael T.
Mizukami, Keijiro
Sekine, Yuya
Hirata, Makoto
Kamatani, Yoichiro
Endo, Mikiko
Inai, Chihiro
Takata, Sadaaki
Ito, Hidemi
Kohno, Takashi
Matsuda, Koichi
Nakamura, Seigo
Sugano, Kokichi
Yoshida, Teruhiko
Nakagawa, Hidewaki
Matsuo, Keitaro
Murakami, Yoshinori
Spurdle, Amanda B.
Kubo, Michiaki
JAMA ONCOLOGY, 2022, 8 (06) : 871 - 878
[3] BRCA1 and BRCA2 cancer risks -: Reply
Chen, Sining
Iversen, Edwin S., Jr.
Parmigiani, Giovanni
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (20) : 3313 - 3314
[4] Breast cancer risk associated with BRCA1 and BRCA2 pathogenic variants in the Eastern Chinese population
Yu, Sanjian
Qiu, Xia
Wang, Zezhou
Xiao, Jialong
Ji, Hui
Shan, Hailin
Shao, Qing
Xia, Heng
Cao, Feng
Li, Jun
Fu, Cuixia
Chen, Liqin
Lu, Xiaofang
Su, Tingting
Yu, Qianqian
Hou, Shengqun
Wang, Honglian
Zheng, Ying
Shao, Zhimin
Liu, Yun
Hu, Zhen
CANCER PATHOGENESIS AND THERAPY, 2025, 3 (02): : 147 - 153
[5] CLINICOPATHOLOGICAL CHARACTERISTICS AND BRCA1 /BRCA2 PATHOGENIC VARIANTS OF PATIENTS WITH BREAST CANCER
Eras, Nazan
Tuncel, Ferah
Altintas, Zuhal
Erden, Sema
POLISH JOURNAL OF PATHOLOGY, 2024, 75 (01) : 1 - 7
[6] Family planning in carriers of BRCA1 and BRCA2 pathogenic variants
Haddad, Jessica M.
Robison, Katina
Beffa, Lindsey
Laprise, Jessica
ScaliaWilbur, Jennifer
Raker, Christina A.
Clark, Melissa A.
Hofstatter, Erin
Dalela, Disha
Brown, Amy
Bradford, Leslie
Toland, Maris
Stuckey, Ashley
JOURNAL OF GENETIC COUNSELING, 2021, 30 (06) : 1570 - 1581
[7] Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants
Barnes, Daniel R.
Rookus, Matti A.
McGuffog, Lesley
Leslie, Goska
Mooij, Thea M.
Dennis, Joe
Mavaddat, Nasim
Adlard, Julian
Ahmed, Munaza
Aittomaki, Kristiina
Andrieu, Nadine
Andrulis, Irene L.
Arnold, Norbert
Arun, Banu K.
Azzollini, Jacopo
Balmana, Judith
Barkardottir, Rosa B.
Barrowdale, Daniel
Benitez, Javier
Berthet, Pascaline
Bialkowska, Katarzyna
Blanco, Amie M.
Blok, Marinus J.
Bonanni, Bernardo
Boonen, Susanne E.
Borg, Ake
Bozsik, Aniko
Bradbury, Angela R.
Brennan, Paul
Brewer, Carole
Brunet, Joan
Buys, Saundra S.
Caldes, Trinidad
Caligo, Maria A.
Campbell, Ian
Christensen, Lise Lotte
Chung, Wendy K.
Claes, Kathleen B. M.
Colas, Chrystelle
Collonge-Rame, Marie-Agnes
Cook, Jackie
Daly, Mary B.
Davidson, Rosemarie
de la Hoya, Miguel
de Putter, Robin
Delnatte, Capucine
Devilee, Peter
Diez, Orland
Ding, Yuan Chun
Domchek, Susan M.
GENETICS IN MEDICINE, 2020, 22 (10) : 1653 - 1666
[8] Management Strategies of Breast Cancer Patients with BRCA1 and BRCA2 Pathogenic Germline Variants
Edaily, Sarah
Abdel-Razeq, Hikmat
ONCOTARGETS AND THERAPY, 2022, 15 : 815 - 826
[9] Prevalence of BRCA1 and BRCA2 pathogenic variants in a large, unselected breast cancer cohort
Li, Jingmei
Wen, Wei Xiong
Eklund, Martin
Kvist, Anders
Eriksson, Mikael
Christensen, Helene Nordahl
Torstensson, Astrid
Bajalica-Lagercrantz, Svetlana
Dunning, Alison M.
Decker, Brennan
Allen, Jamie
Luccarini, Craig
Pooley, Karen
Simard, Jacques
Dorling, Leila
Easton, Douglas F.
Teo, Soo-Hwang
Hall, Per
Borg, Ake
Gronberg, Henrik
Czene, Kamila
INTERNATIONAL JOURNAL OF CANCER, 2019, 144 (05) : 1195 - 1204
[10] BRCA1, BRCA2, and Associated Cancer Risks and Management for Male Patients: A Review
Cheng, Heather H.
Shevach, Jeffrey W.
Castro, Elena
Couch, Fergus J.
Domchek, Susan M.
Eeles, Rosalind A.
Giri, Veda N.
Hall, Michael J.
King, Mary-Claire
Lin, Daniel W.
Loeb, Stacy
Morgan, Todd M.
Offit, Kenneth
Pritchard, Colin C.
Schaeffer, Edward M.
Szymaniak, Brittany M.
Vassy, Jason L.
Katona, Bryson W.
Maxwell, Kara N.
JAMA ONCOLOGY, 2024,

← 1 2 3 4 5 →