Subject(s)
Abnormalities, Multiple/diagnostic imaging , Aorta, Thoracic/diagnostic imaging , Aortography , Cardiovascular Abnormalities/diagnostic imaging , Computed Tomography Angiography , Coronary Angiography , Heart Defects, Congenital/diagnostic imaging , Subclavian Artery/abnormalities , Vascular Malformations/diagnostic imaging , Aorta, Thoracic/abnormalities , Female , Humans , Infant, Newborn , Predictive Value of Tests , Subclavian Artery/diagnostic imagingABSTRACT
Chromium is a well known carcinogen involved in the lung cancer development. Polymorphism of some of the DNA repair genes may be associated with elevated risk of cancerous transformation. In the present study, we investigated the polymorphisms of the following selected members of the base and nucleotide excision repair genes: XPC (Lys939Gln), XPD (Lys751Gln), XRCC1(Arg399Gln), and hOGG1(Ser326Ser), and the risk they present toward the development of lung cancer, with emphasis on the effect of chromium exposure. We analyzed 119 individuals; 50 patients exposed to chromium with diagnosed lung cancer and 69 healthy controls. Genotypes were determined by a PCR-RFLP method. We found a significantly increased risk of lung cancer development in XPD genotype Lys/Gln (OR=1.94; 95% CI=1.10-3.43; p=0.015) and in the gene combinations: XPD Lys/Gln+XPC Lys/Gln (OR=6.5; 95% CI=1.53-27.49; p=0.009) and XPD Lys/Gln+XPC Gln/Gln(OR=5.2; 95% CI=1.07-25.32; p=0.04). In conclusion, gene polymorphisms in the DNA repair genes may underscore the risk of lung cancer development in the chromium-exposed individuals.
Subject(s)
Chromium/toxicity , DNA Repair , Lung Neoplasms/chemically induced , Polymorphism, Genetic , Adult , Aged , Aged, 80 and over , DNA-Binding Proteins/genetics , Environmental Exposure , Female , Genetic Predisposition to Disease , Humans , Lung Neoplasms/genetics , Male , Middle Aged , X-ray Repair Cross Complementing Protein 1 , Xeroderma Pigmentosum Group D Protein/geneticsABSTRACT
hMLH1 and hMSH2 are two of the main members of the mismatch repair (MMR) genes family. Polymorphism of MMR genes is associated with a risk of developing sporadic and hereditary tumors. In the present case-control study, we investigated the promoter polymorphisms of selected mismatch repair genes: hMLH1 (rs1800734) and hMSH2 (rs2303425), and the risk they present regarding the development of lung cancer in the Slovak population. The study included 422 lung cancer cases, 511 controls for hMLH1 gene and 486 controls for hMSH2 gene. Polymorphism was investigated by a PCR-RFLP method. The risk of cancer development was evaluated in both dominant and recessive genetic models. The evaluation of rs1800734 polymorphism in patients in the dominant model showed a significantly decreased risk of lung cancer in the presence of at least one variant allele A (genotype GA and AA) (OR=1.40; 95% CI=1.08-1.82; p=0.01). These findings were equally strong expressed in women (OR=2.00; 95% CI=1.23-3.25; p=0.006). The results for rs2303425 polymorphism revealed an increased risk of lung cancer for variant genotype CC (OR=2.28; 95% CI=1.12-4.63; p=0.024) in the recessive model. A combination of rs1800734 and rs2303425 polymorphisms was shown to be risky for genotype GGCC; OR=3.08; 95% CI=1.09-8.72; p=0.03. The risk appeared even greater in female gender; (OR=11.56; 95% CI=1.33-100.36, 1.26-94.66; p=0.005. We conclude that the genotype of mismatch repair genes underscores the risk of lung cancer development in the Slovak population.
