Two truncating variants in FANCC and breast cancer risk

Dörk, 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.; Bojesen, S. E.; Brauch, H.; Brenner, H.; Burwinkel, B.; Canzian, F.; Chan, T. L.; Chang-Claude, J.; Chanock, S. J.; Choi, J. Y.; Christiansen, H.; Clarke, C. L.; Couch, F. J.; Czene, K.; Daly, M. B.; Dos-Santos-Silva, I.; Dwek, M.; Eccles, D. M.; Ekici, A. B.; Eriksson, M.; Evans, D. G.; Fasching, P. A.; Figueroa, J.; Flyger, H.; Fritschi, L.; Gabrielson, M.; Gago Dominguez, Manuela; Gao, C.; Gapstur, S. M.; García-Closas, M.; García-Sáenz, J. A.; Gaudet, M. M.; Giles, G. G.; Goldberg, M. S.; Goldgar, D. E.; Guénel, P.; Haeberle, L.; Haiman, C. A.; Håkansson, N.; Hall, P.; Hamann, U.; Hartman, M.; Hauke, J.; Hein, A.; Hillemanns, P.; Hogervorst, F. B. L.; Hooning, M. J.; Hopper, J. L.; Howell, T.; Huo, D.; Ito, H.; Iwasaki, M.; Jakubowska, A.; Janni, W.; John, E. M.; Jung, A.; Kaaks, R.; Kang, D.; Kapoor, P. M.; Khusnutdinova, E.; Kim, S. W.; Kitahara, C. M.; Koutros, S.; Kraft, P.; Kristensen, V. N.; Kwong, A.; Lambrechts, D.; Marchand, L. L.; Li, J.; Lindström, S.; Linet, M.; Lo, W. Y.; Long, J.; Lophatananon, A.; Lubiński, J.; Manoochehri, M.; Manoukian, S.; Margolin, S.; Martinez, E.; Matsuo, K.; Mavroudis, D.; Meindl, A.; Menon, U.; Milne, R. L.; Mohd Taib, N. A.; Muir, K.; Mulligan, A. M.; Neuhausen, S. L.; Nevanlinna, H.; Neven, P.; Newman, W. G.; Offit, K.; Olopade, O. I.; Olshan, A. F.; Olson, J. E.; Olsson, H.; Park, S. K.; Park-Simon, T. W.; Peto, J.; Plaseska-Karanfilska, D.; Pohl-Rescigno, E.; Presneau, N.; Rack, B.; Radice, P.; Rashid, M. U.; Rennert, G.; Rennert, H. S.; Romero, A.; Ruebner, M.; Saloustros, E.; Schmidt, M. K.; Schmutzler, R. K.; Schneider, M. O.; Schoemaker, M. J.; Scott, C.; Shen, C. Y.; Shu, X. O.; Simard, J.; Slager, S.; Smichkoska, S.; Southey, M. C.; Spinelli, J. J.; Stone, J.; Surowy, H.; Swerdlow, A. J.; Tamimi, R. M.; Tapper, W. J.; Teo, S. H.; Terry, M. B.; Toland, A. E.; Tollenaar, R. A. E.M; Torres, D.; Torres-Mejía, G.; Troester, M. A.; Truong, T.; Tsugane, S.; Untch, M.; Vachon, C. M.; Ouweland, A. M. W.VD; Veen, E. M. V.; Vijai, J.; Wendt, C.; Wolk, A.; Yu, J. C.; Zheng, W.; Ziogas, A.; Ziv, E.; Dunning, A. M.; Pharoah, P. D. P.; Schindler, D.; Devilee, P.; Easton, D. F.; Investigators, ABCTB; Collaborators, NBCS

doi:10.1038/s41598-019-48804-y

Dörk, 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.; Bojesen, S. E.; Brauch, H.; Brenner, H.; Burwinkel, B.; Canzian, F.; Chan, T. L.; Chang-Claude, J.; Chanock, S. J.; Choi, J. Y.; Christiansen, H.; Clarke, C. L.; Couch, F. J.; Czene, K.; Daly, M. B.; Dos-Santos-Silva, I.; Dwek, M.; Eccles, D. M.; Ekici, A. B.; Eriksson, M.; Evans, D. G.; Fasching, P. A.; Figueroa, J.; Flyger, H.; Fritschi, L.; Gabrielson, M.; Gago Dominguez, Manuela; Gao, C.; Gapstur, S. M.; García-Closas, M.; García-Sáenz, J. A.; Gaudet, M. M.; Giles, G. G.; Goldberg, M. S.; Goldgar, D. E.; Guénel, P.; Haeberle, L.; Haiman, C. A.; Håkansson, N.; Hall, P.; Hamann, U.; Hartman, M.; Hauke, J.; Hein, A.; Hillemanns, P.; Hogervorst, F. B. L.; Hooning, M. J.; Hopper, J. L.; Howell, T.; Huo, D.; Ito, H.; Iwasaki, M.; Jakubowska, A.; Janni, W.; John, E. M.; Jung, A.; Kaaks, R.; Kang, D.; Kapoor, P. M.; Khusnutdinova, E.; Kim, S. W.; Kitahara, C. M.; Koutros, S.; Kraft, P.; Kristensen, V. N.; Kwong, A.; Lambrechts, D.; Marchand, L. L.; Li, J.; Lindström, S.; Linet, M.; Lo, W. Y.; Long, J.; Lophatananon, A.; Lubiński, J.; Manoochehri, M.; Manoukian, S.; Margolin, S.; Martinez, E.; Matsuo, K.; Mavroudis, D.; Meindl, A.; Menon, U.; Milne, R. L.; Mohd Taib, N. A.; Muir, K.; Mulligan, A. M.; Neuhausen, S. L.; Nevanlinna, H.; Neven, P.; Newman, W. G.; Offit, K.; Olopade, O. I.; Olshan, A. F.; Olson, J. E.; Olsson, H.; Park, S. K.; Park-Simon, T. W.; Peto, J.; Plaseska-Karanfilska, D.; Pohl-Rescigno, E.; Presneau, N.; Rack, B.; Radice, P.; Rashid, M. U.; Rennert, G.; Rennert, H. S.; Romero, A.; Ruebner, M.; Saloustros, E.; Schmidt, M. K.; Schmutzler, R. K.; Schneider, M. O.; Schoemaker, M. J.; Scott, C.; Shen, C. Y.; Shu, X. O.; Simard, J.; Slager, S.; Smichkoska, S.; Southey, M. C.; Spinelli, J. J.; Stone, J.; Surowy, H.; Swerdlow, A. J.; Tamimi, R. M.; Tapper, W. J.; Teo, S. H.; Terry, M. B.; Toland, A. E.; Tollenaar, R. A. E.M; Torres, D.; Torres-Mejía, G.; Troester, M. A.; Truong, T.; Tsugane, S.; Untch, M.; Vachon, C. M.; Ouweland, A. M. W.VD; Veen, E. M. V.; Vijai, J.; Wendt, C.; Wolk, A.; Yu, J. C.; Zheng, W.; Ziogas, A.; Ziv, E.; Dunning, A. M.; Pharoah, P. D. P.; Schindler, D.; Devilee, P.; Easton, D. F.; Investigators, ABCTB; Collaborators, NBCS

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Identifiers

URI: http://hdl.handle.net/20.500.11940/15426

PMID: 31467304

DOI: 10.1038/s41598-019-48804-y

ISSN: 2045-2322

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Sci Rep. 2019 Aug 29;9(1):12524. doi: 10.1038/s41598-019-48804-y. (1.045Mb)

Date issued

2019

Journal title

Scientific Reports

Type of content

Artigo

DeCS

variación genética | estudios de casos y controles | humanos | predisposición genética a la enfermedad

MeSH

Humans | Genetic Variation | Case-Control Studies | Genetic Predisposition to Disease

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.

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