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The R72P P53 mutation is associated with familial breast cancer in Jewish women
- Source :
- British Journal of Cancer
- Publication Year :
- 2005
- Publisher :
- Springer Science and Business Media LLC, 2005.
-
Abstract
- BRCA1/BRCA2 mutations account for a substantial proportion of familial breast cancer, but clearly mutations in additional genes exist, one candidate being the p53 gene. To evaluate its putative involvement in inherited predisposition to breast/ovarian cancer in Jewish high-risk women, mutational analysis of the p53 gene (exons 4-9) was carried out using exon-specific polymerase chain reaction followed by denaturing gradient gel electrophoresis (DGGE) analysis, complemented by DNA sequencing of abnormally migrating fragments. Overall, 132 Jewish breast cancer patient non-BRCA1/2 mutation carriers and 167 average risk controls (Ashkenazi (n=60), non-Ashkenazi (n=107)) were genotyped, and no inactivating p53 germline mutations were detected. Consistent migration abnormalities were noted in 167 fragments, 134 of which were shown to be the Arg72Pro polymorphism, whereas migration abnormalities in fragments containing exons 4 (n=2) and 6 (n=23) and introns 3 (n=4) and 9 (n=4) corresponded to five previously described polymorphisms. Allele distribution of the R72P missense mutation between ethnically diverse Jewish breast cancer cases and average risk controls showed significant differences: among non-Ashkenazi breast cancer cases, 62.5%, 33.3% and 4.2% were homozygous, heterozygous and homozygous for the Arg72, Arg72Pro and the Pro72 polymorphism, respectively, whereas for controls, the distribution was 22.4%, 65.4% and 12.2%, respectively (P=0.00052), and among Ashkenazi breast cancer cases, allele distribution was 68.5%, 29.6% and 1.9%, whereas for controls, the distribution was 50%, 40% and 10%, respectively (P=0.0125). We conclude that arginine homozygosity at codon 72 of the p53 gene is associated with a significant increased breast cancer risk in Jewish high-risk population.
- Subjects :
- Adult
Cancer Research
Genes, BRCA2
Population
Genes, BRCA1
Breast Neoplasms
Biology
law.invention
Exon
Breast cancer
Germline mutation
law
medicine
Humans
Missense mutation
Genetic Predisposition to Disease
DGGE
skin and connective tissue diseases
education
Gene
Germ-Line Mutation
Polymerase chain reaction
Aged
Arg72Pro mutation
Genetics
education.field_of_study
P53 gene
Genetics and Genomics
Middle Aged
Genes, p53
medicine.disease
Molecular biology
Oncology
Jews
germline mutations
inherited predisposition to breast cancer
Female
Ovarian cancer
Subjects
Details
- ISSN :
- 15321827 and 00070920
- Volume :
- 92
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....15a215de39a33151b5d79da9c282be01