A polymorphism at codon 133 of the tumor suppressor RASSF1A is associated with tumorous alteration of the breast

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Undraga Schagdarsurengin - , AG Tumorgenetik der Medizinischen Fakultät, Halle/Saale, Germany. (Author)
  • Claudia Seidel - , Martin Luther University Halle-Wittenberg (Author)
  • Eva J Ulbrich - (Author)
  • Heinz Kölbl - (Author)
  • Jürgen Dittmer - (Author)
  • Reinhard Dammann - (Author)

Abstract

The tumor suppressor gene RASSF1A is inactivated or mutated in different tumor entities including breast cancer. The frequency of the genomic variants of RASSF1A in patients with breast tumors has not been evaluated. We studied the association between ten nucleotide polymorphisms of RASSF1A and the risk of breast cancer in 178 cases with tumorous alterations of mammary tissue (including 141 carcinomas and 37 fibroadenomas) and 70 controls by SSCP and sequencing. Polymorphisms of RASSF1A were found at codon 28 and codon 133. The distribution of polymorphisms at codon 28 showed no significant difference between the patient groups: 5 of 178 (2.8%) in patients with tumorous alterations and 2 of 70 (2.9%) in control patients. However, the Gright curved arrow T polymorphism (GCTright curved arrow TCT; Alaright curved arrow Ser) at codon 133, which alters the microtubule association and stabilization domain of RASSF1A, exhibited a different genotype distribution: 29 out of 141 (20.6%) patients with breast carcinoma and 9 out of 37 (24.3%) patients with fibroadenoma harbored mutant T-alleles. However, only in 2 out of 70 (2.9%) controls, the mutant T-allele was detected and therefore the frequency was significantly diminished compared to tumorous alterations (Fisher's exact test: carcinomas vs. controls, p = 0.0003; fibroadenoma vs. controls, p = 0.001). From five probands with homozygous TT-genotype at codon 133, three were diagnosed with carcinomas and two with fibroadenomas. Our data indicate that the mutant T-allele of RASSF1A at codon 133 is correlated with an increased number of breast tumors.

Details

Original languageEnglish
Pages (from-to)185-91
Number of pages7
JournalInternational journal of oncology
Volume27
Issue number1
Publication statusPublished - Jul 2005
Peer-reviewedYes
Externally publishedYes

External IDs

Scopus 24644435402

Keywords

Sustainable Development Goals

Keywords

  • Adult, Aged, Alleles, Breast/pathology, Breast Neoplasms/genetics, Codon, Cohort Studies, DNA Primers/chemistry, Exons, Female, Fibroadenoma/pathology, Genotype, Heterozygote, Homozygote, Humans, Middle Aged, Polymerase Chain Reaction, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Polymorphism, Single-Stranded Conformational, Protein Structure, Tertiary, Sequence Analysis, DNA, Serine/chemistry, Temperature, Tumor Suppressor Proteins/genetics