Relationship between TP53 tumour suppressor gene mutations and smoking-related bulky DNA adducts in a lung cancer study population from Hungary.
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 (32)P-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/10(8) 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.
Anna
Lívia
L
Department of Molecular Environmental Epidemiology, National Institute of Environmental Health, H-1097 Budapest, Hungary.
Holmila
Reetta
R
Kovács
Katalin
K
Gyorffy
Erika
E
Gyori
Zoltán
Z
Segesdi
Judit
J
Minárovits
János
J
Soltész
Ibolya
I
Kostic
Szilárd
S
Csekeo
Attila
A
Husgafvel-Pursiainen
Kirsti
K
Schoket
Bernadette
B
D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics*; D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000209:etiology / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics*; D018736:DNA Adducts; D005260:Female; D006801:Humans; D006814:Hungary; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012907:Smoking / Q000009:adverse effects*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D018736:DNA Adducts; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53