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01-12-2021 | Breast Cancer | Research article

Diagnostic chest X-rays and breast cancer risk among women with a hereditary predisposition to breast cancer unexplained by a BRCA1 or BRCA2 mutation

Authors: Maximiliano Ribeiro Guerra, Juliette Coignard, Séverine Eon-Marchais, Marie-Gabrielle Dondon, Dorothée Le Gal, Juana Beauvallet, Noura Mebirouk, Muriel Belotti, Olivier Caron, Marion Gauthier-Villars, Isabelle Coupier, Bruno Buecher, Alain Lortholary, Jean-Pierre Fricker, Paul Gesta, Catherine Noguès, Laurence Faivre, Pascaline Berthet, Elisabeth Luporsi, Capucine Delnatte, Valérie Bonadona, Christine M. Maugard, Pascal Pujol, Christine Lasset, Michel Longy, Yves-Jean Bignon, Claude Adenis-Lavignasse, Laurence Venat-Bouvet, Hélène Dreyfus, Laurence Gladieff, Isabelle Mortemousque, Séverine Audebert-Bellanger, Florent Soubrier, Sophie Giraud, Sophie Lejeune-Dumoulin, Jean-Marc Limacher, Jean Chiesa, Anne Fajac, Anne Floquet, François Eisinger, Julie Tinat, Sandra Fert-Ferrer, Chrystelle Colas, Thierry Frebourg, Francesca Damiola, Laure Barjhoux, Eve Cavaciuti, Sylvie Mazoyer, Anne Tardivon, Fabienne Lesueur, Dominique Stoppa-Lyonnet, Nadine Andrieu

Published in: Breast Cancer Research | Issue 1/2021

Abstract

Background

Diagnostic ionizing radiation is a risk factor for breast cancer (BC). BC risk increases with increased dose to the chest and decreases with increased age at exposure, with possible effect modification related to familial or genetic predisposition. While chest X-rays increase the BC risk of BRCA1/2 mutation carriers compared to non-carriers, little is known for women with a hereditary predisposition to BC but who tested negative for a BRCA1 or BRCA2 (BRCA1/2) mutation.

Methods

We evaluated the effect of chest X-rays from diagnostic medical procedures in a dataset composed of 1552 BC cases identified through French family cancer clinics and 1363 unrelated controls. Participants reported their history of X-ray exposures in a detailed questionnaire and were tested for 113 DNA repair genes. Logistic regression and multinomial logistic regression models were used to assess the association with BC.

Results

Chest X-ray exposure doubled BC risk. A 3% increased BC risk per additional exposure was observed. Being 20 years old or younger at first exposure or being exposed before first full-term pregnancy did not seem to modify this risk. Birth after 1960 or carrying a rare likely deleterious coding variant in a DNA repair gene other than BRCA1/2 modified the effect of chest X-ray exposure.

Conclusion

Ever/never chest X-ray exposure increases BC risk 2-fold regardless of age at first exposure and, by up to 5-fold when carrying 3 or more rare variants in a DNA repair gene.

Further studies are needed to evaluate other DNA repair genes or variants to identify those which could modify radiation sensitivity. Identification of subpopulations that are more or less susceptible to ionizing radiation is important and potentially clinically relevant.

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Title: Diagnostic chest X-rays and breast cancer risk among women with a hereditary predisposition to breast cancer unexplained by a BRCA1 or BRCA2 mutation
Authors: Maximiliano Ribeiro Guerra
Juliette Coignard
Séverine Eon-Marchais
Marie-Gabrielle Dondon
Dorothée Le Gal
Juana Beauvallet
Noura Mebirouk
Muriel Belotti
Olivier Caron
Marion Gauthier-Villars
Isabelle Coupier
Bruno Buecher
Alain Lortholary
Jean-Pierre Fricker
Paul Gesta
Catherine Noguès
Laurence Faivre
Pascaline Berthet
Elisabeth Luporsi
Capucine Delnatte
Valérie Bonadona
Christine M. Maugard
Pascal Pujol
Christine Lasset
Michel Longy
Yves-Jean Bignon
Claude Adenis-Lavignasse
Laurence Venat-Bouvet
Hélène Dreyfus
Laurence Gladieff
Isabelle Mortemousque
Séverine Audebert-Bellanger
Florent Soubrier
Sophie Giraud
Sophie Lejeune-Dumoulin
Jean-Marc Limacher
Jean Chiesa
Anne Fajac
Anne Floquet
François Eisinger
Julie Tinat
Sandra Fert-Ferrer
Chrystelle Colas
Thierry Frebourg
Francesca Damiola
Laure Barjhoux
Eve Cavaciuti
Sylvie Mazoyer
Anne Tardivon
Fabienne Lesueur
Dominique Stoppa-Lyonnet
Nadine Andrieu
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Breast Cancer
Breast Cancer
Published in: Breast Cancer Research / Issue 1/2021
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/s13058-021-01456-1

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