1. ¹Human Cancer Genetics Programme, Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain
2. ²National Epidemiology Centre, Instituto de Salud Carlos III & CIBERESP, Madrid, Spain
3. ³Human Cancer Genetics Programme, Genotyping Unit, Spanish National Cancer Centre (CNIO), Madrid, Spain
4. ⁴Division of Molecular Gynaeco-Oncology, Department of Obstetrics and Gynaecology, University of Cologne, Cologne, Germany
5. ⁵Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
6. ⁶Department of Obstetrics and Gynaecology, Technical University, Munich, Germany
7. ⁷Department of Obstetrics and Gynaecology, University of Schleswig-Holstein, Campus Kiel, Germany
8. ⁸Institute of Human Genetics, University of Münster, Münster, Germany
9. ⁹Department of Obstetrics and Gynaecology, Molecular Genetics Laboratory, University of Düsseldorf, Düsseldorf, Germany
10. ¹⁰Institute of Human Genetics, Charite-University Medical Centre, Berlin, Germany
11. ¹¹Institute of Cellular and Molecular Pathology, Medical University, Hannover, Germany
12. ¹²Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
13. ¹³German Cancer Research Center, Molecular Genetics of Breast Cancer, Heidelberg, Germany
14. ¹⁴Cancer Genetic Counselling Progam, Catalan Institute of Oncology (ICO), Barcelona, Spain
15. ¹⁵Molecular Diagnostics Laboratory IRRP, NCSR Demokritos, Athens, Greece
16. ¹⁶Genetics Service, Hospital de Sant Pau, Barcelona, Spain
17. ¹⁷Oncogenetics Laboratory, Hospital Vall d'Hebron, Barcelona, Spain
18. ¹⁸Medical Genetics Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
19. ¹⁹Unit of Genetic Susceptibility to Cancer, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
20. ²⁰IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy
21. ²¹Department of Obstetrics and Gynecology, Helsinki University Central Hospital (HUCH), Helsinki, Finland
22. ²²Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA
23. ²³Cancer Research UK Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK

Correspondence: Dr A Osorio, Human Genetics Group, Spanish National Cancer Centre (CNIO), C/Melchor Fernández Almagro 3, 28029 Madrid, Spain. E-mail: aosorio@cnio.es

Received 4 July 2007; Accepted 30 July 2008.

Abstract

The close functional relationship between p53 and the breast cancer susceptibility genes BRCA1 and BRCA2 has promoted the investigation of various polymorphisms in the p53 gene as possible risk modifiers in BRCA1/2 mutation carriers. Specifically, two polymorphisms in p53, c.97-147ins16bp and p.Arg72Pro have been analysed as putative breast cancer susceptibility variants, and it has been recently reported that a p53 haplotype combining the absence of the 16-bp insertion and the presence of proline at codon 72 (No Ins-72Pro) was associated with an earlier age at the onset of the first primary tumour in BRCA2 mutation carriers in the Spanish population. In this study, we have evaluated this association in a series of 2932 BRCA1/2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2.