Reduced DNA repair capacity in laryngeal cancer subjects. A comparison of phenotypic and genotypic results.
The impact of genetic factors on laryngeal cancer risk was studied in relation to DNA repair capacity on the phenotypic and genotypic level. DNA lesions induced by bleomycin or S9-activated benzo[a]pyrene were determined in blood lymphocytes using the alkaline comet assay. Laryngeal cancer subjects (n = 52) were shown to have higher levels of spontaneous and mutagen-induced DNA damage as compared to healthy controls (n = 56). A level of spontaneous DNA damage tended to increase with tumour grading. A percentage of individuals with an efficient DNA repair was higher in controls than in cancer subjects for both used mutagens. The distribution of polymorphic variants of XPD, XRCC1 and XRCC3 DNA repair genes in the group of laryngeal cancer subjects (n = 293), subjects with second primary tumours (n = 84) and in the matched controls (n = 322) was estimated by PCR-based genotyping. Five polymorphisms were studied in 3 DNA repair genes. There were found only 2 XPD alleles significantly overrepresented in laryngeal cancer that could be interpreted as an increase in genetic risk. There were no significant differences in distribution of 'risk' and 'protective' genotypes between single primary and second primary tumours. Altogether, the established phenotypic deficit of DNA repair in laryngeal cancer subjects was only partly confirmed by overrepresentation of 'risk' genotypes of the studied DNA repair genes.
Gajecka
Marzena
M
Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
Rydzanicz
Malgorzata
M
Jaskula-Sztul
Renata
R
Wierzbicka
Martgorzata
M
Szyfter
Witold
W
Szyfter
Krzysztof
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007822:Laryngeal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011044:Poland / Q000453:epidemiology; D011110:Polymorphism, Genetic; D011336:Probability; D011379:Prognosis; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human