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Variation in breast cancer risk with mutation position, smoking, alcohol, and chest X-ray history, in the French National BRCA1/2 carrier cohort (GENEPSO)

  • Epidemiology
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Abstract

Germline mutations in BRCA1/2 confer a high risk of breast cancer (BC), but the magnitude of this risk varies according to various factors. Although controversial, there are data to support the hypothesis of allelic-risk heterogeneity. We assessed variation in BC risk according to the location of mutations recorded in the French study GENEPSO. Since the women in this study were selected from high-risk families, oversampling of affected women was eliminated by using a weighted Cox-regression model. Women were censored at the date of diagnosis when affected by any cancer, or the date of interview when unaffected. A total of 990 women were selected for the analysis: 379 were classified as affected, 611 as unaffected. For BRCA1, there was some evidence of a central region where the risk of BC is lower (codons 374–1161) (HR = 0.59, P = 0.04). For BRCA2, there was a strong evidence for a region at decreased risk (codons 957–1827) (HR = 0.35, P = 0.005) and for one at increased risk (codons 2546–2968) (HR = 3.56, P = 0.01). Moreover, we found an important association between radiation exposure from chest X-rays and BC risk (HR = 4.29, P < 10−3) and a positive association between smoking more than 21 pack-years and BC risk (HR = 2.09, P = 0.04). No significant variation in BC risk associated with chest X-ray exposure, smoking, and alcohol consumption was found according to the location of the mutation in BRCA1 and BRCA2. Our findings are consistent with those suggesting that the risk of BC is lower in the central regions of BRCA1/2. A new high-risk region in BRCA2 is described. Taking into account environmental and lifestyle modifiers, the location of mutations might be important in the clinical management of BRCA mutation carriers.

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Acknowledgments

This GENEPSO study is supported by the Fondation de France and the Ligue Nationale Contre le Cancer. The authors thank Marie-Lise Manche-Thévenot, Claude Picard, and Irwin Piot (hôpital René Huguenin, Saint Cloud, France) who provided technical assistance.

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Authors and Affiliations

  1. Institut National de la Santé et de la Recherche Médicale, Unité U900, 26 rue d’Ulm, 75248, Paris Cedex 05, France

    Julie Lecarpentier & Nadine Andrieu

  2. Institut Curie, Centre de Recherche – Service de Biostatistiques, 26 rue d’Ulm, 75248, Paris Cedex 05, France

    Julie Lecarpentier & Nadine Andrieu

  3. Ecole des Mines de Paris, Paris Tech, 77300, Fontainebleau, France

    Julie Lecarpentier & Nadine Andrieu

  4. Institut Curie, Hôpital René Huguenin, 92210, Saint-Cloud, France

    Catherine Noguès & Emmanuelle Mouret-Fourme

  5. Institut National de la Santé et de la Recherche Médicale, Unité U509, Service de Génétique Oncologique, Institut Curie, Université Paris-Descartes, 26 rue d’Ulm, 75248, Paris, France

    Dominique Stoppa-Lyonnet

  6. Centre Léon Bérard, Département de Santé Publique, 28 rue Laënnec, 69737, Lyon, France

    Christine Lasset

  7. Institut de Cancérologie Gustave Roussy, Service d’Oncologie Génétique, 39 rue Camille Desmoulins, 94800, Villejuif, France

    Olivier Caron

  8. Centre Paul Strauss, Unité d’Oncologie, 3 rue Porte de l’Hopital, 67065, Strasbourg, France

    Jean-Pierre Fricker

  9. Institut Claudius Regaud, Service d’Oncologie Médicale, 20–24 rue du Pont Saint Pierre, 31052, Toulouse, France

    Laurence Gladieff

  10. Centre Georges Francois Leclerc, Oncogénétique and Hôpital d’Enfants, Service de Génétique Médicale, 10 boulevard du Mal de Lattre de Tassigny, 21079, Dijon, France

    Laurence Faivre

  11. Institut Paoli-Calmettes, Département d’Oncologie Génétique, 232 boulevard Ste Marguerite, 13273, Marseille, France

    Hagay Sobol

  12. C.H.R. Georges Renon, Pôle Oncologie, 40 avenue Charles de Gaulle, 79021, Niort, France

    Paul Gesta

  13. Centre Antoine Lacassagne, Unité d’Oncogénétique, 33 avenue de Valombrose, Nice, 06189, France

    Marc Frenay

  14. Centre Alexis Vautrin, 6 avenue de Bourgogne, 54511, Vandoeuvre-les-Nancy, France

    Elisabeth Luporsi

  15. Hopital Arnaud de Villeneuve, CHU Montpellier, Service de Génétique médicale et Oncogénétique, 371 ave du Doyen Gaston Giraud, 34295, Montpellier, France

    Isabelle Coupier

  16. Institut National de la Santé et de la Recherche Médicale, Unité U735 and Laboratoire d’Oncogénétique, Hôpital René Huguenin, Saint-Cloud, France

    Rosette Lidereau

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  1. Julie Lecarpentier
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  2. Catherine Noguès
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  3. Emmanuelle Mouret-Fourme
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  4. Dominique Stoppa-Lyonnet
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  6. Olivier Caron
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  9. Laurence Faivre
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GENEPSO

Corresponding author

Correspondence to Nadine Andrieu.

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GENEPSO Collaborating Centers are listed in Appendix.

Appendix

Appendix

GENEPSO Collaborating Centers

Coordinating Center, Hôpital René Huguenin/Institut Curie,Saint Cloud: Catherine Noguès, Emmanuelle Fourme, Rosette Lidereau; Etienne Rouleau, Sandrine Caputo.

Collaborating Centers: Institut Curie, Paris: Dominique Stoppa-Lyonnet, Marion Gauthier-Villars; Bruno Buecher, Institut Gustave Roussy, Villejuif: Olivier Caron; Hôpital René Huguenin/Institut Curie, Saint Cloud: Catherine Noguès, Liliane Demange; Centre Paul Strauss, Strasbourg: Jean-Pierre Fricker; Centre Léon Bérard, Lyon: Christine Lasset, Valérie Bonadona; Centre François Baclesse, Caen: Pascaline Berthet; Hôpital d’Enfants CHU Dijon – Centre Georges François Leclerc, Dijon: Laurence Faivre; Centre Alexis Vautrin, Vandoeuvre-les-Nancy: Elisabeth Luporsi; Centre Antoine Lacassagne, Nice: Marc Frénay; Institut Claudius Regaud, Toulouse: Laurence Gladieff; Réseau Oncogénétique Poitou Charente, Niort: Paul Gesta; Institut Paoli-Calmettes, Marseille: Hagay Sobol, François Eisinger, Laetitia Huiart; Institut Bergonié, Bordeaux: Michel Longy; Centre Eugène Marquis, Rennes: Catherine Dugast; GH Pitié Salpétrière, Paris: Chrystelle Colas, Florent Soubrier; CHU Arnaud de Villeneuve, Montpellier: Isabelle Coupier, Pascal Pujol; Centres Paul Papin, and Catherine de Sienne, Angers, Nantes: Alain Lortholary; Centre Oscar Lambret, Lille: Philippe Vennin, Claude Adenis; Institut Jean Godinot, Reims: Tan Dat Nguyen; Centre René Gauducheau, Nantes: Capucine Delnatte; Centre Henri Becquerel, Rouen: Annick Rossi, Julie Tinat, Isabelle Tennevet; Hôpital Civil, Strasbourg: Jean-Marc Limacher, Christine Maugard; Hôpital Centre Jean Perrin, Clermont-Ferrand: Yves-Jean Bignon; Polyclinique Courlancy, Reims: Liliane Demange; Clinique Sainte Catherine, Avignon: Hélène Dreyfus; Hôpital Saint-Louis, Paris: Odile Cohen-Haguenauer; CHRU Dupuytren, Limoges: Brigitte Gilbert; Couple-Enfant-CHU de Grenoble: Dominique Leroux; Hôpital de la Timone, Marseille: Hélène Zattara-Cannoni; Inserm U900, Ecole des Mines de Paris, ParisTech, Service de Biostatistiques, Institut Curie, Paris: Nadine Andrieu; Inserm U535, Villejuif: Catherine Bonaïti; Inserm U379, Marseille: Claire Julian-Reynier.

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Lecarpentier, J., Noguès, C., Mouret-Fourme, E. et al. Variation in breast cancer risk with mutation position, smoking, alcohol, and chest X-ray history, in the French National BRCA1/2 carrier cohort (GENEPSO). Breast Cancer Res Treat 130, 927–938 (2011). https://doi.org/10.1007/s10549-011-1655-3

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