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

Maximiliano Ribeiro Guerra 1, 2, 3, 4, 5 Juliette Coignard 1, 2, 3, 4 Séverine Eon-Marchais 1, 2, 3, 4 Marie-Gabrielle Dondon 1, 2, 3, 4 Dorothée Le Gal 1, 2, 3, 4 Juana Beauvallet 1, 2, 3, 4 Noura Mebirouk 1, 2, 3, 4 Muriel Belotti 2 Olivier Caron 6, 7 Marion Gauthier-Villars 2 Isabelle Coupier 8, 9 Bruno Buecher 2 Alain Lortholary 10 Jean-Pierre Fricker 11 Paul Gesta 12 Catherine Noguès 13, 14 Laurence Faivre 15, 16 Pascaline Berthet 17 Elisabeth Luporsi 18, 19 Capucine Delnatte 20 Valérie Bonadona 21, 22 Christine Maugard 23 Pascal Pujol 8, 9 Christine Lasset 21, 22 Michel Longy 24 Yves-Jean Bignon 25, 26 Claude Adenis-Lavignasse 27 Laurence Venat-Bouvet 28 Hélène Dreyfus 29, 30 Laurence Gladieff 31, 32 Isabelle Mortemousque 33 Séverine Audebert-Bellanger 34 Florent Soubrier 35 Sophie Giraud 36, 37 Sophie Lejeune-Dumoulin 38 Jean-Marc Limacher 39 Jean Chiesa 40 Anne Fajac 35 Anne Floquet 24 François Eisinger 13, 14 Julie Tinat 41 Sandra Fert-Ferrer 42 Chrystelle Colas 2, 43 Thierry Frebourg 44 Francesca Damiola 22 Laure Barjhoux 45 Eve Cavaciuti 1, 2, 3, 4 Sylvie Mazoyer 46 Anne Tardivon 2 Fabienne Lesueur 1, 2, 3, 4 Dominique Stoppa-Lyonnet 2, 47, 48 Nadine Andrieu 1, 2, 3, 4
Abstract : 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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Submitted on : Friday, September 17, 2021 - 11:14:35 AM
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Maximiliano Ribeiro Guerra, Juliette Coignard, Séverine Eon-Marchais, Marie-Gabrielle Dondon, Dorothée Le Gal, et al.. Diagnostic chest X-rays and breast cancer risk among women with a hereditary predisposition to breast cancer unexplained by a BRCA1 or BRCA2 mutation. Breast Cancer Research, BioMed Central, 2021, 23 (1), ⟨10.1186/s13058-021-01456-1⟩. ⟨hal-03345365⟩



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