| dc.contributor.author | HUGHES, DAVID JOHN | |
| dc.date.accessioned | 2011-11-21T16:44:44Z | |
| dc.date.available | 2011-11-21T16:44:44Z | |
| dc.date.issued | 2009 | |
| dc.date.submitted | 2009 | en |
| dc.identifier.citation | Sinilnikova OM, Antoniou AC, Simard J, Healey S, Leone M, Sinnett D, Spurdle AB, Beesley J, Chen X, Greene MH, Loud JT, Lejbkowicz F, Rennert G, Dishon S, Andrulis IL, Domchek SM, Nathanson KL, Manoukian S, Radice P, Konstantopoulou I, Blanco I, Laborde AL, Duran M, Osorio A, Benitez J, Hamann U, Hogervorst FB, van Os TA, Gille HJ, Peock S, Cook M, Luccarini C, Evans DG, Lalloo F, Eeles R, Pichert G, Davidson R, Cole T, Cook J, Paterson J, Brewer C, Hughes DJ, Coupier I, Giraud S, Coulet F, Colas C, Soubrier F, Rouleau E, Bieche I, Lidereau R, Demange L, Nogues C, Lynch HT, Schmutzler RK, Versmold B, Engel C, Meindl A, Arnold N, Sutter C, Deissler H, Schaefer D, Froster UG, Aittomaki K, Nevanlinna H, McGuffog L, Easton DF, Chenevix-Trench G, Stoppa-Lyonnet D, The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers., British Journal of Cancer, 101, 8, 2009, 1456-60 | en |
| dc.identifier.other | Y | |
| dc.identifier.uri | http://hdl.handle.net/2262/60886 | |
| dc.description | PUBLISHED | en |
| dc.description.abstract | The TP53 pathway, in which TP53 and its negative regulator MDM2 are the central elements, has an important role in carcinogenesis, particularly in BRCA1- and BRCA2-mediated carcinogenesis. A single nucleotide polymorphism (SNP) in the promoter region of MDM2 (309T>G, rs2279744) and a coding SNP of TP53 (Arg72Pro, rs1042522) have been shown to be of functional significance.
METHODS:
To investigate whether these SNPs modify breast cancer risk for BRCA1 and BRCA2 mutation carriers, we pooled genotype data on the TP53 Arg72Pro SNP in 7011 mutation carriers and on the MDM2 309T>G SNP in 2222 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analysed using a Cox proportional hazards model within a retrospective likelihood framework.
RESULTS:
No association was found between these SNPs and breast cancer risk for BRCA1 (TP53: per-allele hazard ratio (HR)=1.01, 95% confidence interval (CI): 0.93-1.10, P(trend)=0.77; MDM2: HR=0.96, 95%CI: 0.84-1.09, P(trend)=0.54) or for BRCA2 mutation carriers (TP53: HR=0.99, 95%CI: 0.87-1.12, P(trend)=0.83; MDM2: HR=0.98, 95%CI: 0.80-1.21, P(trend)=0.88). We also evaluated the potential combined effects of both SNPs on breast cancer risk, however, none of their combined genotypes showed any evidence of association.
CONCLUSION:
There was no evidence that TP53 Arg72Pro or MDM2 309T>G, either singly or in combination, influence breast cancer risk in BRCA1 or BRCA2 mutation carriers. | en |
| dc.description.sponsorship | The CIMBA data management, DE, LM, SP, MC and EMBRACE are supported by Cancer Research UK Grants C1287/A10118 and C1287/A8874. CL is supported by Cancer Research UK Grant C8197/A10123. ACA is a Cancer Research ? UK Senior Cancer Research Fellow.
Jacques Simard is Chairholder of the Canada Research Chair in Oncogenetics. This work was supported by the Canadian Institutes of Health Research for the `CIHR Team of Prediction and Communication of Familial Risks of Breast Cancer? program. Daniel Sinnett holds the Francois-Karl Viau Chair in Pediatric Oncogenomics and is a scholar of the Fonds de la Recherche en Sante du Quebec (FRSQ).
We thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. The kConFab Clinical Follow Up Study has been funded by NHMRC grants 145684, 288704 and 454508. ABS and GCT are NHMRC fellows.
We gratefully acknowledge the contribution of Dr Jeffery P Struewing and Marbin Pineda for their laboratory support of this project. Drs Greene and Loud were supported by funding from the Intramural Research Program of the US National Cancer Institute, and from research contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Rockville, MD, USA.
The NICCC thanks the laboratory technicians Mrs. Irena Rimon and Mrs. Ana Gurtovnik for their technical support.
OCGN: We thank Mona Gill and Nayana Weerasooriya for assistance and we acknowledge funding from Cancer Care Ontario.
We thank Alicia Barroso, Concepcion Hernandez and Anna Gonzalez for their technical support. The CNIO study was partially funded by the Asociacion Espa?ola Contra el Cancer (AECC), the Fundacion Marato and the project PI081120 from the Ministry of Science and Innovation.
We thank Diana Torres and Muhammad U Rashid for providing DNA samples and supplying data. We thank Antje Seidel-Renkert for expert technical assistance. The DKFZ study was supported by the DKFZ.
The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI 2007-3756.
The investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. RE, EB and L D'M are also supported by Cancer Research UK Grant C5047/A8385. DGE and FL are supported the NIHR Biomedical Research Centre, Manchester.
We wish to thank all the GEMO collaborating members (Cancer Genetics Network `Groupe Genetique et Cancer?, Federation Nationale des Centres de Lutte Contre le Cancer, France) for their contribution to this study. The GEMO study was supported by the Ligue National Contre le Cancer and the Association `Le cancer du sein, parlons-en!? Award.
We thank Juliane Koehler for her excellent technical assistance and the 12 centers of the GC-HBOC (German Consortium of Hereditary Breast and Ovarian Cancer) for providing samples and clinical data. GC-HBOC is supported by a grant of the German Cancer Aid (grant 107054) and the Center for Molecular Medicine Cologne (grant TV93) to Rita K Schmutzler.
We thank Drs Kirsimari Aaltonen, Carl Blomqvist and RN Hanna Jantti for their help with the patient data and Dr Johanna Tommiska for her kind help with the genetic analyses. The Finnish Cancer registry is gratefully acknowledged for the cancer data. The HEBCS study has been financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (110663), Finnish Cancer Society and the Sigrid Juselius Foundation. | en |
| dc.format.extent | 1456-60 | en |
| dc.language.iso | en | en |
| dc.relation.ispartofseries | British Journal of Cancer; | |
| dc.relation.ispartofseries | 101; | |
| dc.relation.ispartofseries | 8; | |
| dc.rights | Y | en |
| dc.subject | Oncology | en |
| dc.subject | Breast cancer | en |
| dc.title | The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers. | en |
| dc.type | Journal Article | en |
| dc.type.supercollection | scholarly_publications | en |
| dc.type.supercollection | refereed_publications | en |
| dc.identifier.peoplefinderurl | http://people.tcd.ie/hughesd4 | |
| dc.identifier.rssinternalid | 75986 | |
| dc.identifier.rssuri | http://dx.doi.org/10.1038/sj.bjc.6605279 | en |
