Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/209296
Title: BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer
Authors: Shimelis, Hermela
Mesman, Romy LS
Von Nicolai, Catharina
Ehlen, Asa
Guidugli, Lucia
Martin, Charlotte
Calleja, Fabienne MGR
Meeks, Huong
Hallberg, Emily
Hinton, Jamie
Lilyquist, Jenna
Hu, Chunling
Aalfs, Cora M
Aittomaki, 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
Bruning, Thomas
Burwinkel, Barbara
Chang-Claude, Jenny
Chenevix-Trench, Georgia
Cheng, Ching-Yu
Choi, Ji-Yeob
Collee, J Margriet
Cox, Angela
Cross, Simon S
Czene, Kamila
Darabi, Hatef
Dennis, Joe
Dork, Thilo
dos-Santos-Silva, Isabel
Dunning, Alison M
Fasching, Peter A
Figueroa, Jonine
Flyger, Henrik
Garcia-Closas, Montserrat
Giles, Graham G
Glendon, Gord
Guenel, 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
Le Marchand, Loic
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, Pauld DP
Pylkas, 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, Therese
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
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
UNKNOWN CLINICAL-SIGNIFICANCE
CELL-BASED ASSAY
UNCERTAIN SIGNIFICANCE
OVARIAN-CANCER
UNCLASSIFIED VARIANTS
SEQUENCE VARIANTS
DNA-BINDING
FUNCTIONAL-EVALUATION
GENES
CLASSIFICATION
Issue Date: 1-Jun-2017
Publisher: AMER ASSOC CANCER RESEARCH
Citation: Shimelis, Hermela, Mesman, Romy LS, Von Nicolai, Catharina, Ehlen, Asa, Guidugli, Lucia, Martin, Charlotte, Calleja, Fabienne MGR, Meeks, Huong, Hallberg, Emily, Hinton, Jamie, Lilyquist, Jenna, Hu, Chunling, Aalfs, Cora M, Aittomaki, 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, Bruning, Thomas, Burwinkel, Barbara, Chang-Claude, Jenny, Chenevix-Trench, Georgia, Cheng, Ching-Yu, Choi, Ji-Yeob, Collee, J Margriet, Cox, Angela, Cross, Simon S, Czene, Kamila, Darabi, Hatef, Dennis, Joe, Dork, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M, Fasching, Peter A, Figueroa, Jonine, Flyger, Henrik, Garcia-Closas, Montserrat, Giles, Graham G, Glendon, Gord, Guenel, 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, Le Marchand, Loic, 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, Pauld DP, Pylkas, 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, Therese, 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 (2017-06-01). BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer. CANCER RESEARCH 77 (11) : 2789-2799. ScholarBank@NUS Repository.
Abstract: 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.
Source Title: CANCER RESEARCH
URI: https://scholarbank.nus.edu.sg/handle/10635/209296
ISSN: 00085472
15387445
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