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Influence of the MDM2 single nucleotide polymorphism SNP309 on tumour development in BRCA1 mutation carriers

Influence of the MDM2 single nucleotide polymorphism SNP309 on tumour development in BRCA1 mutation carriers
Influence of the MDM2 single nucleotide polymorphism SNP309 on tumour development in BRCA1 mutation carriers
Background

The MDM2 gene encodes a negative regulator of the p53 tumour suppressor protein. A single nucleotide polymorphism (SNP) in the MDM2 promoter (a T to G exchange at nucleotide 309) has been reported to produce accelerated tumour formation in individuals with inherited p53 mutations. We have investigated the effect of the MDM2 SNP309 on clinical outcome in a cohort of patients with germline mutations of BRCA1.

Methods

Genomic DNA was obtained for 102 healthy controls and 116 patients with established pathogenic mutations of BRCA1 and Pyrosequencing technology™ was used to determine the genotype at the MDM2 SNP309 locus.

Results

The polymorphism was present in 52.9% of the controls (G/T in 37.3% and G/G in 15.6%) and 58.6% of the BRCA1 mutation carriers (47.4% G/T and 11.2% G/G). Incidence of malignancy in female BRCA1 carriers was not significantly higher in SNP309 carriers than in wildtype (T/T) individuals (72.7% vs. 75.6%, p = 1.00). Mean age of diagnosis of first breast cancer was 41.2 years in the SNP309 G/G genotype carriers, 38.6 years in those with the SNP309 G/T genotype and 39.0 years in wildtype subjects (p = 0.80).

Conclusion

We found no evidence that the MDM2 SNP309 accelerates tumour development in carriers of known pathogenic germline mutations of BRCA1.
single nucleotide, proto-oncogene proteins c-mdm2, protein, genes, aged, humans, proteins, cancer, genetic predisposition to disease, methods, human, breast neoplasms, diagnosis, middle aged, adolescent, female, mutation, breast cancer, incidence, patients, germ-line mutation, 80 and over, research, genetics, brca1, polymorphism, cohort, research support, genotype, adult, dna, case-control studies, proto-oncogene proteins
1471-2407
Copson, Ellen R.
a94cdbd6-f6e2-429d-a7c0-462c7da0e92b
White, Helen E.
6bf1f3df-e2f1-491b-9df1-9173afa943cf
Blaydes, Jeremy P.
e957f999-fd91-4f77-ad62-5b4ef069b15b
Robinson, David O.
9db1b26b-6c2b-4ac5-879e-20f8a2dc30ec
Johnson, Peter W.
3f6068ce-171e-4c2c-aca9-dc9b6a37413f
Eccles, Diana M.
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Copson, Ellen R.
a94cdbd6-f6e2-429d-a7c0-462c7da0e92b
White, Helen E.
6bf1f3df-e2f1-491b-9df1-9173afa943cf
Blaydes, Jeremy P.
e957f999-fd91-4f77-ad62-5b4ef069b15b
Robinson, David O.
9db1b26b-6c2b-4ac5-879e-20f8a2dc30ec
Johnson, Peter W.
3f6068ce-171e-4c2c-aca9-dc9b6a37413f
Eccles, Diana M.
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23

Copson, Ellen R., White, Helen E., Blaydes, Jeremy P., Robinson, David O., Johnson, Peter W. and Eccles, Diana M. (2006) Influence of the MDM2 single nucleotide polymorphism SNP309 on tumour development in BRCA1 mutation carriers. BMC Cancer, 6 (80). (doi:10.1186/1471-2407-6-80).

Record type: Article

Abstract

Background

The MDM2 gene encodes a negative regulator of the p53 tumour suppressor protein. A single nucleotide polymorphism (SNP) in the MDM2 promoter (a T to G exchange at nucleotide 309) has been reported to produce accelerated tumour formation in individuals with inherited p53 mutations. We have investigated the effect of the MDM2 SNP309 on clinical outcome in a cohort of patients with germline mutations of BRCA1.

Methods

Genomic DNA was obtained for 102 healthy controls and 116 patients with established pathogenic mutations of BRCA1 and Pyrosequencing technology™ was used to determine the genotype at the MDM2 SNP309 locus.

Results

The polymorphism was present in 52.9% of the controls (G/T in 37.3% and G/G in 15.6%) and 58.6% of the BRCA1 mutation carriers (47.4% G/T and 11.2% G/G). Incidence of malignancy in female BRCA1 carriers was not significantly higher in SNP309 carriers than in wildtype (T/T) individuals (72.7% vs. 75.6%, p = 1.00). Mean age of diagnosis of first breast cancer was 41.2 years in the SNP309 G/G genotype carriers, 38.6 years in those with the SNP309 G/T genotype and 39.0 years in wildtype subjects (p = 0.80).

Conclusion

We found no evidence that the MDM2 SNP309 accelerates tumour development in carriers of known pathogenic germline mutations of BRCA1.

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More information

Published date: 24 March 2006
Keywords: single nucleotide, proto-oncogene proteins c-mdm2, protein, genes, aged, humans, proteins, cancer, genetic predisposition to disease, methods, human, breast neoplasms, diagnosis, middle aged, adolescent, female, mutation, breast cancer, incidence, patients, germ-line mutation, 80 and over, research, genetics, brca1, polymorphism, cohort, research support, genotype, adult, dna, case-control studies, proto-oncogene proteins

Identifiers

Local EPrints ID: 40669
URI: https://eprints.soton.ac.uk/id/eprint/40669
ISSN: 1471-2407
PURE UUID: 6ccb7274-bbc8-4eff-8bdb-0268871c34fc
ORCID for Jeremy P. Blaydes: ORCID iD orcid.org/0000-0001-8525-0209
ORCID for Peter W. Johnson: ORCID iD orcid.org/0000-0003-2306-4974

Catalogue record

Date deposited: 07 Jul 2006
Last modified: 18 May 2019 00:36

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Contributors

Author: Ellen R. Copson
Author: Helen E. White
Author: David O. Robinson
Author: Diana M. Eccles

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