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Two Truncating Variants in FANCC and Breast Cancer Risk

Citation

Dörk, Thilo; Peterlongo, Paolo; Mannermaa, Arto; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Ahearn, Thomas; Andrulis, Irene L.; Anton-Culver, Hoda; & Arndt, Volker, et al. (2019). Two Truncating Variants in FANCC and Breast Cancer Risk. Scientific Reports, 9, 12524. PMCID: PMC6715680

Abstract

Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.

URL

http://dx.doi.org/10.1038/s41598-019-48804-y

Reference Type

Journal Article

Journal Title

Scientific Reports

Author(s)

Dörk, Thilo
Peterlongo, Paolo
Mannermaa, Arto
Bolla, Manjeet K.
Wang, Qin
Dennis, Joe
Ahearn, Thomas
Andrulis, Irene L.
Anton-Culver, Hoda
Arndt, Volker
Aronson, Kristan J.
Augustinsson, Annelie
Freeman, Laura E. Beane
Beckmann, Matthias W.
Beeghly-Fadiel, Alicia
Behrens, Sabine
Bermisheva, Marina
Blomqvist, Carl
Bogdanova, Natalia V.
Bojesen, Stig Egil
Brauch, Hiltrud
Brenner, Hermann
Burwinkel, Barbara
Canzian, Federico
Chan, Tsun L.
Chang-Claude, Jenny
Chanock, Stephen J.
Choi, Ji-Yeob
Christiansen, Hans
Clarke, Christine L.
Couch, Fergus J.
Czene, Kamila
Daly, Mary B.
Dos-Santos-Silva, Isabel
Dwek, Miriam
Eccles, Diana M.
Ekici, Arif B.
Eriksson, Mikael
Evans, D. Gareth
Fasching, Peter A.
Figueroa, Jonine
Flyger, Henrik
Fritschi, Lin
Gabrielson, Marike
Gago-Dominguez, Manuela
Gao, Chi
Gapstur, Susan M.
García-Closas, Montserrat
García-Sáenz, José A.
Gaudet, Mia M.
Giles, Graham G.
Goldberg, Mark S.
Goldgar, David E.
Guénel, Pascal
Haeberle, Lothar
Haiman, Christopher A.
Håkansson, Niclas
Hall, Per
Hamann, Ute
Hartman, Mikael
Hauke, Jan
Hein, Alexander
Hillemanns, Peter
Hogervorst, Frans B. L.
Hooning, Maartje J.
Hopper, John L.
Howell, Tony
Huo, Dezheng
Ito, Hidemi
Iwasaki, Motoki
Jakubowska, Anna
Janni, Wolfgang
John, Esther M.
Jung, Audrey
Kaaks, Rudolf
Kang, Daehee
Kapoor, Pooja Middha
Khusnutdinova, Elza
Kim, Sung-Won
Kitahara, Cari M.
Koutros, Stella
Kraft, Peter
Kristensen, Vessela N.
Kwong, Ava
Lambrechts, Diether
Le Marchand, Loic
Li, Jingmei
Lindström, Sara
Linet, Martha
Lo, Wing-Yee
Long, Jirong
Lophatananon, Artitaya
Lubiński, Jan
Manoochehri, Mehdi
Manoukian, Siranoush
Margolin, Sara
Martinez, Elena
Matsuo, Keitaro
Mavroudis, Dimitris
Meindl, Alfons
Menon, Usha
Milne, Roger L.
Mohd Taib, Nur Aishah
Muir, Kenneth
Mulligan, Anna Marie
Neuhausen, Susan L.
Nevanlinna, Heli
Neven, Patrick
Newman, William G.
Offit, Kenneth
Olopade, Olufunmilayo I.
Olshan, Andrew F.
Olson, Janet E.
Olsson, Håkan
Park, Sue K.
Park-Simon, Tjoung-Won
Peto, Julian
Plaseska-Karanfilska, Dijana
Pohl-Rescigno, Esther
Presneau, Nadege
Rack, Brigitte
Radice, Paolo
Rashid, Muhammad U.
Rennert, Gad
Rennert, Hedy S.
Romero, Atocha
Ruebner, Matthias
Saloustros, Emmanouil
Schmidt, Marjanka K.
Schmutzler, Rita K.
Schneider, Michael O.
Schoemaker, Minouk J.
Scott, Christopher
Shen, Chen-Yang
Shu, Xiao-Ou
Simard, Jacques
Slager, Susan L.
Smichkoska, Snezhana
Southey, Melissa C.
Spinelli, John J.
Stone, Jennifer
Surowy, Harald
Swerdlow, Anthony J.
Tamimi, Rulla M.
Tapper, William J.
Teo, Soo H.
Terry, Mary Beth
Toland, Amanda E.
Tollenaar, Rob A. E. M.
Torres, Diana
Torres-Mejía, Gabriela
Troester, Melissa A.
Truong, Thérèse
Tsugane, Shoichiro
Untch, Michael
Vachon, Celine M.
Ouweland, Ans M. W. van den
Veen, Elke M. van
Vijai, Joseph
Wendt, Camilla
Wolk, Alicja
Yu, Jyh-Cherng
Zheng, Wei
Ziogas, Argyrios
Ziv, Elad
ABCTB Investigators
NBCS Collaborators
Dunning, Alison M.
Pharoah, Paul D. P.
Schindler, Detlev
Devilee, Peter
Easton, Douglas F.

Year Published

2019

Volume Number

9

Pages

12524

PMCID

PMC6715680

Reference ID

13072