Two truncating variants in FANCC and breast cancer risk

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

doi:10.1038/s41598-019-48804-y

Two truncating variants in FANCC and breast cancer risk

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

Western Sydney University

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

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.

Original language	English
Number of pages	14
Journal	Scientific Reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41598-019-48804-y
Publication status	Published - 2019

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10.1038/s41598-019-48804-y

Cite this

Dork, T., Peterlongo, P., Mannermaa, A., Bolla, M. K., Wang, Q., Dennis, J., Ahearn, T., Andrulis, I. L., Anton-Culver, H., Arndt, V., Aronson, K. J., Augustinsson, A., Freeman, L. E. B., Beckmann, M. W., Beeghly-Fadiel, A., Behrens, S., Bermisheva, M., Blomqvist, C., Bogdanova, N. V., ... et al. (2019). Two truncating variants in FANCC and breast cancer risk. Scientific Reports, 9(1). https://doi.org/10.1038/s41598-019-48804-y

@article{9e27f8b9890e484793b256e434505b2b,

title = "Two truncating variants in FANCC and breast cancer risk",

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.",

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

year = "2019",

doi = "10.1038/s41598-019-48804-y",

language = "English",

volume = "9",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

Dork, T, Peterlongo, P, Mannermaa, A, Bolla, MK, Wang, Q, Dennis, J, Ahearn, T, Andrulis, IL, Anton-Culver, H, Arndt, V, Aronson, KJ, Augustinsson, A, Freeman, LEB, Beckmann, MW, Beeghly-Fadiel, A, Behrens, S, Bermisheva, M, Blomqvist, C, Bogdanova, NV, Bojesen, SE, Brauch, H, Brenner, H, Burwinkel, B, Canzian, F, Chan, TL, Chang-Claude, J, Chanock, SJ, Choi, J-Y, Christiansen, H, Clarke, CL, Couch, FJ, Czene, K, Daly, MB, dos-Santos-Silva, I, Dwek, M, Eccles, DM, Ekici, AB, Eriksson, M, Evans, DG, Fasching, PA, Figueroa, J, Flyger, H, Fritschi, L, Gabrielson, M, Gago-Dominguez, M, Gao, C, Gapstur, SM, Garcia-Closas, M, Garcia-Saenz, JA, Gaudet, MM, Giles, GG, Goldberg, MS, Goldgar, DE, Guenel, P, Haeberle, L, Haiman, CA, Hakansson, N, Hall, P, Hamann, U, Hartman, M, Hauke, J, Hein, A, Hillemanns, P, Hogervorst, FBL, Hooning, MJ, Hopper, JL, Howell, T, Huo, D, Ito, H, Iwasaki, M, Jakubowska, A, Janni, W, John, EM, Jung, A, Kaaks, R, Kang, D, Kapoor, PM, Khusnutdinova, E, Kim, S-W, Kitahara, CM, Koutros, S, Kraft, P, Kristensen, VN, Kwong, A, Lambrechts, D, Marchand, LL, Li, J, Lindstrom, S, Linet, M, Lo, W-Y, Long, J, Lophatananon, A, Lubinski, J, Manoochehri, M, Manoukian, S, Margolin, S, Martinez, E, Matsuo, K, Mavroudis, D, Meindl, A, Menon, U, Milne, RL, Taib, NAM, Muir, K, Mulligan, AM, Neuhausen, SL, Nevanlinna, H, Neven, P, Newman, WG, Offit, K, Olopade, OI, Olshan, AF, Olson, JE, Olsson, H, Park, SK, Park-Simon, T-W, Peto, J, Plaseska-Karanfilska, D, Pohl-Rescigno, E, Presneau, N, Rack, B, Radice, P, Rashid, MU, Rennert, G, Rennert, HS, Romero, A, Ruebner, M, Saloustros, E, Schmidt, MK, Schmutzler, RK, Schneider, MO, Schoemaker, MJ, Scott, C, Shen, C-Y, Shu, X-O, Simard, J, Slager, S, Smichkoska, S, Southey, MC, Spinelli, JJ, Stone, J, Surowy, H, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Teo, SH, Terry, MB, Toland, AE, Tollenaar, RAEM, Torres, D, Torres-Mejía, G, Troester, MA, Truong, T, Tsugane, S, Untch, M, Vachon, CM, Van Den Ouweland, AMW, Van Veen, EM, Vijai, J, Wendt, C, Wolk, A, Yu, J-C, Zheng, W, Ziogas, A, Ziv, E, Balleine, R, Baxter, R, Braye, S, Carpenter, J, Dahlstrom, J, Forbes, J, Lee, CS & et al. 2019, 'Two truncating variants in FANCC and breast cancer risk', Scientific Reports, vol. 9, no. 1. https://doi.org/10.1038/s41598-019-48804-y

TY - JOUR

T1 - Two truncating variants in FANCC and breast cancer risk

AU - Dork, Thilo

AU - Peterlongo, Paolo

AU - Mannermaa, Arto

AU - Bolla, Manjeet K.

AU - Wang, Qin

AU - Dennis, Joe

AU - Ahearn, Thomas

AU - Andrulis, Irene L.

AU - Anton-Culver, Hoda

AU - Arndt, Volker

AU - Aronson, Kristan J.

AU - Augustinsson, Annelie

AU - Freeman, Laura E. Beane

AU - Beckmann, Matthias W.

AU - Beeghly-Fadiel, Alicia

AU - Behrens, Sabine

AU - Bermisheva, Marina

AU - Blomqvist, Carl

AU - Bogdanova, Natalia V.

AU - Bojesen, Stig E.

AU - Brauch, Hiltrud

AU - Brenner, Hermann

AU - Burwinkel, Barbara

AU - Canzian, Federico

AU - Chan, Tsun L.

AU - Chang-Claude, Jenny

AU - Chanock, Stephen J.

AU - Choi, Ji-Yeob

AU - Christiansen, Hans

AU - Clarke, Christine L.

AU - Couch, Fergus J.

AU - Czene, Kamila

AU - Daly, Mary B.

AU - dos-Santos-Silva, Isabel

AU - Dwek, Miriam

AU - Eccles, Diana M.

AU - Ekici, Arif B.

AU - Eriksson, Mikael

AU - Evans, D. Gareth

AU - Fasching, Peter A.

AU - Figueroa, Jonine

AU - Flyger, Henrik

AU - Fritschi, Lin

AU - Gabrielson, Marike

AU - Gago-Dominguez, Manuela

AU - Gao, Chi

AU - Gapstur, Susan M.

AU - Garcia-Closas, Montserrat

AU - Garcia-Saenz, Jose A.

AU - Gaudet, Mia M.

AU - Giles, Graham G.

AU - Goldberg, Mark S.

AU - Goldgar, David E.

AU - Guenel, Pascal

AU - Haeberle, Lothar

AU - Haiman, Christopher A.

AU - Hakansson, Niclas

AU - Hall, Per

AU - Hamann, Ute

AU - Hartman, Mikael

AU - Hauke, Jan

AU - Hein, Alexander

AU - Hillemanns, Peter

AU - Hogervorst, Frans B. L.

AU - Hooning, Maartje J.

AU - Hopper, John L.

AU - Howell, Tony

AU - Huo, Dezheng

AU - Ito, Hidemi

AU - Iwasaki, Motoki

AU - Jakubowska, Anna

AU - Janni, Wolfgang

AU - John, Esther M.

AU - Jung, Audrey

AU - Kaaks, Rudolf

AU - Kang, Daehee

AU - Kapoor, Pooja Middha

AU - Khusnutdinova, Elza

AU - Kim, Sung-Won

AU - Kitahara, Cari M.

AU - Koutros, Stella

AU - Kraft, Peter

AU - Kristensen, Vessela N.

AU - Kwong, Ava

AU - Lambrechts, Diether

AU - Marchand, Loic Le

AU - Li, Jingmei

AU - Lindstrom, Sara

AU - Linet, Martha

AU - Lo, Wing-Yee

AU - Long, Jirong

AU - Lophatananon, Artitaya

AU - Lubinski, Jan

AU - Manoochehri, Mehdi

AU - Manoukian, Siranoush

AU - Margolin, Sara

AU - Martinez, Elena

AU - Matsuo, Keitaro

AU - Mavroudis, Dimitris

AU - Meindl, Alfons

AU - Menon, Usha

AU - Milne, Roger L.

AU - Taib, Nur Aishah Mohd

AU - Muir, Kenneth

AU - Mulligan, Anna Marie

AU - Neuhausen, Susan L.

AU - Nevanlinna, Heli

AU - Neven, Patrick

AU - Newman, William G.

AU - Offit, Kenneth

AU - Olopade, Olufunmilayo I.

AU - Olshan, Andrew F.

AU - Olson, Janet E.

AU - Olsson, Hakan

AU - Park, Sue K.

AU - Park-Simon, Tjoung-Won

AU - Peto, Julian

AU - Plaseska-Karanfilska, Dijana

AU - Pohl-Rescigno, Esther

AU - Presneau, Nadege

AU - Rack, Brigitte

AU - Radice, Paolo

AU - Rashid, Muhammad U.

AU - Rennert, Gad

AU - Rennert, Hedy S.

AU - Romero, Atocha

AU - Ruebner, Matthias

AU - Saloustros, Emmanouil

AU - Schmidt, Marjanka K.

AU - Schmutzler, Rita K.

AU - Schneider, Michael O.

AU - Schoemaker, Minouk J.

AU - Scott, Christopher

AU - Shen, Chen-Yang

AU - Shu, Xiao-Ou

AU - Simard, Jacques

AU - Slager, Susan

AU - Smichkoska, Snezhana

AU - Southey, Melissa C.

AU - Spinelli, John J.

AU - Stone, Jennifer

AU - Surowy, Harald

AU - Swerdlow, Anthony J.

AU - Tamimi, Rulla M.

AU - Tapper, William J.

AU - Teo, Soo H.

AU - Terry, Mary Beth

AU - Toland, Amanda E.

AU - Tollenaar, Rob A. E. M.

AU - Torres, Diana

AU - Torres-Mejía, Gabriela

AU - Troester, Melissa A.

AU - Truong, Therese

AU - Tsugane, Shoichiro

AU - Untch, Michael

AU - Vachon, Celine M.

AU - Van Den Ouweland, Ans M. W.

AU - Van Veen, Elke M.

AU - Vijai, Joseph

AU - Wendt, Camilla

AU - Wolk, Alicja

AU - Yu, Jyh-Cherng

AU - Zheng, Wei

AU - Ziogas, Argyrios

AU - Ziv, Elad

AU - Balleine, Rosemary

AU - Baxter, Robert

AU - Braye, Stephen

AU - Carpenter, Jane

AU - Dahlstrom, Jane

AU - Forbes, John

AU - Lee, C. Soon

AU - et al., null

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

UR - http://hdl.handle.net/1959.7/uws:65223

U2 - 10.1038/s41598-019-48804-y

DO - 10.1038/s41598-019-48804-y

M3 - Article

SN - 2045-2322

VL - 9

JO - Scientific Reports

JF - Scientific Reports

IS - 1

ER -

Two truncating variants in FANCC and breast cancer risk

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