دورية أكاديمية
BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer.
| العنوان: | BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer. |
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| المؤلفون: | Shimelis, Hermela, Mesman, Romy LS, Von Nicolai, Catharina, Ehlen, Asa, Guidugli, Lucia, Martin, Charlotte, Calléja, Fabienne MGR, Meeks, Huong, Hallberg, Emily, Hinton, Jamie, Lilyquist, Jenna, Hu, Chunling, Aalfs, Cora M, Aittomäki, Kristiina, Andrulis, Irene, Anton-Culver, Hoda, Arndt, Volker, Beckmann, Matthias W, Benitez, Javier, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Borresen-Dale, Anne-Lise, Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Broeks, Annegien, Brouwers, Barbara, Brüning, Thomas, Burwinkel, Barbara, Chang-Claude, Jenny, Chenevix-Trench, Georgia, Cheng, Ching-Yu, Choi, Ji-Yeob, Collée, J Margriet, Cox, Angela, Cross, Simon S, Czene, Kamila, Darabi, Hatef, Dennis, Joe, Dörk, Thilo, Dos-Santos-Silva, Isabel, Dunning, Alison M, Fasching, Peter A, Figueroa, Jonine, Flyger, Henrik, García-Closas, Montserrat, Giles, Graham G, Glendon, Gord, Guénel, Pascal, Haiman, Christopher A, Hall, Per, Hamann, Ute, Hartman, Mikael, Hogervorst, Frans B, Hollestelle, Antoinette, Hopper, John L, Ito, Hidemi, Jakubowska, Anna, Kang, Daehee, Kosma, Veli-Matti, Kristensen, Vessela, Lai, Kah-Nyin, Lambrechts, Diether, Marchand, Loic Le, Li, Jingmei, Lindblom, Annika, Lophatananon, Artitaya, Lubinski, Jan, Machackova, Eva, Mannermaa, Arto, Margolin, Sara, Marme, Frederik, Matsuo, Keitaro, Miao, Hui, Michailidou, Kyriaki, Milne, Roger L, Muir, Kenneth, Neuhausen, Susan L, Nevanlinna, Heli, Olson, Janet E, Olswold, Curtis, Oosterwijk, Jan JC, Osorio, Ana, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul DP, Pylkäs, Katri, Radice, Paolo, Rashid, Muhammad Usman, Rhenius, Valerie, Rudolph, Anja, Sangrajrang, Suleeporn, Sawyer, Elinor J, Schmidt, Marjanka K, Schoemaker, Minouk J, Seynaeve, Caroline, Shah, Mitul, Shen, Chen-Yang, Shrubsole, Martha, Shu, Xiao-Ou, Slager, Susan, Southey, Melissa C, Stram, Daniel O, Swerdlow, Anthony, Teo, Soo H, Tomlinson, Ian, Torres, Diana, Truong, Thérèse, van Asperen, Christi J, van der Kolk, Lizet E, Wang, Qin, Winqvist, Robert, Wu, Anna H, Yu, Jyh-Cherng, Zheng, Wei, Zheng, Ying, Leary, Jennifer, Walker, Logan, Foretova, Lenka, Fostira, Florentia, Claes, Kathleen BM, Varesco, Liliana, Moghadasi, Setareh, Easton, Douglas F, Spurdle, Amanda, Devilee, Peter, Vrieling, Harry, Monteiro, Alvaro NA, Goldgar, David E, Carreira, Aura, Vreeswijk, Maaike PG, Couch, Fergus J, for kConFab/AOCS Investigators, for NBCS Collaborators |
| بيانات النشر: | American Association for Cancer Research (AACR) //dx.doi.org/10.1158/0008-5472.can-16-2568 Cancer Res |
| سنة النشر: | 2017 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Aged, Amino Acid Substitution, Animals, BRCA2 Protein, Breast Neoplasms, Case-Control Studies, Female, Genotype, Germ-Line Mutation, Humans, Mice, Mutation, Missense, Risk |
| الوصف: | Breast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case-control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A>C, p.Tyr3035Ser (OR = 2.52; P = 0.04), and BRCA1 c.5096G>A, p.Arg1699Gln (OR = 4.29; P = 0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G>A, p.Gly2508Ser (OR = 2.68; P = 0.004), and c.8187G>T, p.Lys2729Asn (OR = 1.4; P = 0.004) were associated with moderate and low risks of breast cancer among Asians. Functional characterization of the BRCA2 variants using four quantitative assays showed reduced BRCA2 activity for p.Tyr3035Ser compared with wild-type. Overall, our results show how BRCA2 missense variants that influence protein function can confer clinically relevant, moderately increased risks of breast cancer, with potential implications for risk management guidelines in women with these specific variants. Cancer Res; 77(11); 2789-99. ©2017 AACR. ; This work was supported in part by NIH grants CA116167, CA176785, CA192393, an NIH specialized program of research excellence (SPORE) in breast cancer to the Mayo Clinic (P50 CA116201), the Breast Cancer Research Foundation (to F.C. Couch), the ATIP-AVENIR CNRS/INSERM Young Investi- gator grant 201201, EC-Marie Curie Career Integration grant CIG293444, Institute National du CancerINCa-DGOS_8706 (to A. Carreira), the Dutch Cancer Society KWF (UL2012-5649 to M.P.G. Vreeswijk), the Australian National Health and Medical Research Council (ID#1010719), and The Cancer Council Queensland (ID#1086286 to A. Spurdle). BCAC data management was funded by ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Print-Electronic; application/pdf |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/264361Test |
| DOI: | 10.17863/CAM.9851 |
| الإتاحة: | https://doi.org/10.17863/CAM.9851Test https://www.repository.cam.ac.uk/handle/1810/264361Test |
| رقم الانضمام: | edsbas.335C2172 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.9851 |
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