Relationship between TP53 tumour suppressor gene mutations and smoking-related bulky DNA adducts in a lung cancer study population from Hungary

Lívia Anna, Reetta Holmila, Katalin Kovács, Erika Gyrffy, Zoltán Gyri, Judit Segesdi, J. Mináróvits, Ibolya Soltész, Szilárd Kosti, Attila Cseke, Kirsti Husgafvel-Pursiainen, B. Schoket

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Lung cancer rate in Hungary is one of the highest in the world among men and also very high among women, for reasons not clearly understood yet. The aim of the study was to explore characteristics of DNA damage and TP53 gene mutations in lung cancer from Hungary. Tissue samples from 104 lung resections for lung cancer patients, both men and women, operated on for non-small cell lung cancer, specifically, primary squamous cell carcinoma or adenocarcinoma were studied. Of the cases, 37% smoked up to the surgery, 24% stopped smoking within 1 year before the surgery, 26% stopped smoking more than a year before the surgery and 13% never smoked. TP53 mutations were detected by denaturant gradient gel electrophoresis, automated capillary electrophoresis single-strand conformation polymorphism and sequencing. Bulky DNA adduct levels were determined by 32P-post-labelling in non-tumorous lung tissue. In total, 45% (47/104) of the cases carried TP53 mutation. The prevalence of TP53 mutations was statistically significantly associated with duration of smoking, tumour histology and gender. Smokers had approximately twice as high bulky adduct level as the combined group of former- and never-smokers (10.9 ± 6.5 versus 5.5 ± 3.4 adducts/108 nucleotides). The common base change G → T transversion (8/43; 19%) was detected exclusively in smokers. For the first time, we demonstrate that most carriers of G → T transversions had also a high level of bulky DNA adducts in their non-tumourous lung tissue. Our study provides evidence for a high burden of molecular alterations occurring concurrently in the lung of lung cancer patients.

Original languageEnglish
Pages (from-to)475-480
Number of pages6
JournalMutagenesis
Volume24
Issue number6
DOIs
Publication statusPublished - Nov 2009

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Genetic Suppression
DNA Adducts
Hungary
Tumor Suppressor Genes
Surgery
Tumors
Lung Neoplasms
Genes
Smoking
Tissue
Lung
Mutation
Population
Capillary electrophoresis
Histology
Electrophoresis
Polymorphism
Labeling
Conformations
p53 Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Relationship between TP53 tumour suppressor gene mutations and smoking-related bulky DNA adducts in a lung cancer study population from Hungary. / Anna, Lívia; Holmila, Reetta; Kovács, Katalin; Gyrffy, Erika; Gyri, Zoltán; Segesdi, Judit; Mináróvits, J.; Soltész, Ibolya; Kosti, Szilárd; Cseke, Attila; Husgafvel-Pursiainen, Kirsti; Schoket, B.

In: Mutagenesis, Vol. 24, No. 6, 11.2009, p. 475-480.

Research output: Contribution to journalArticle

Anna, L, Holmila, R, Kovács, K, Gyrffy, E, Gyri, Z, Segesdi, J, Mináróvits, J, Soltész, I, Kosti, S, Cseke, A, Husgafvel-Pursiainen, K & Schoket, B 2009, 'Relationship between TP53 tumour suppressor gene mutations and smoking-related bulky DNA adducts in a lung cancer study population from Hungary', Mutagenesis, vol. 24, no. 6, pp. 475-480. https://doi.org/10.1093/mutage/gep031
Anna, Lívia ; Holmila, Reetta ; Kovács, Katalin ; Gyrffy, Erika ; Gyri, Zoltán ; Segesdi, Judit ; Mináróvits, J. ; Soltész, Ibolya ; Kosti, Szilárd ; Cseke, Attila ; Husgafvel-Pursiainen, Kirsti ; Schoket, B. / Relationship between TP53 tumour suppressor gene mutations and smoking-related bulky DNA adducts in a lung cancer study population from Hungary. In: Mutagenesis. 2009 ; Vol. 24, No. 6. pp. 475-480.
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