Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk.

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Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk.

Sci Rep. 2020 Jun 16;10(1):9688

Authors: Liu J, Prager-van der Smissen WJC, Collée JM, Bolla MK, Wang Q, Michailidou K, Dennis J, Ahearn TU, Aittomäki K, Ambrosone CB, Andrulis IL, Anton-Culver H, Antonenkova NN, Arndt V, Arnold N, Aronson KJ, Augustinsson A, Auvinen P, Becher H, Beckmann MW, Behrens S, Bermisheva M, Bernstein L, Bogdanova NV, Bogdanova-Markov N, Bojesen SE, Brauch H, Brenner H, Briceno I, Brucker SY, Brüning T, Burwinkel B, Cai Q, Cai H, Campa D, Canzian F, Castelao JE, Chang-Claude J, Chanock SJ, Choi JY, Christiaens M, Clarke CL, NBCS Collaborators, Couch FJ, Czene K, Daly MB, Devilee P, Dos-Santos-Silva I, Dwek M, Eccles DM, Eliassen AH, Fasching PA, Figueroa J, Flyger H, Fritschi L, Gago-Dominguez M, Gapstur SM, García-Closas M, García-Sáenz JA, Gaudet MM, Giles GG, Goldberg MS, Goldgar DE, Guénel P, Haiman CA, Håkansson N, Hall P, Harrington PA, Hart SN, Hartman M, Hillemanns P, Hopper JL, Hou MF, Hunter DJ, Huo D, ABCTB Investigators, Ito H, Iwasaki M, Jakimovska M, Jakubowska A, John EM, Kaaks R, Kang D, Keeman R, Khusnutdinova E, Kim SW, Kraft P, Kristensen VN, Kurian AW, Le Marchand L, Li J, Lindblom A, Lophatananon A, Luben RN, Lubiński J, Mannermaa A, Manoochehri M, Manoukian S, Margolin S, Mariapun S, Matsuo K, Maurer T, Mavroudis D, Meindl A, Menon U, Milne RL, Muir K, Mulligan AM, Neuhausen SL, Nevanlinna H, Offit K, Olopade OI, Olson JE, Olsson H, Orr N, Park SK, Peterlongo P, Peto J, Plaseska-Karanfilska D, Presneau N, Rack B, Rau-Murthy R, Rennert G, Rennert HS, Rhenius V, Romero A, Ruebner M, Saloustros E, Schmutzler RK, Schneeweiss A, Scott C, Shah M, Shen CY, Shu XO, Simard J, Sohn C, Southey MC, Spinelli JJ, Tamimi RM, Tapper WJ, Teo SH, Terry MB, Torres D, Truong T, Untch M, Vachon CM, van Asperen CJ, Wolk A, Yamaji T, Zheng W, Ziogas A, Ziv E, Torres-Mejía G, Dörk T, Swerdlow AJ, Hamann U, Schmidt MK, Dunning AM, Pharoah PDP, Easton DF, Hooning MJ, Martens JWM, Hollestelle A

Abstract
In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859-1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482-1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.

PMID: 32546843 [PubMed – in process]