Association of polymorphism of folate metabolism genes and chromosomal aberrations in blood cells of lung cancer patients

In the presented «case-control» study 338 residents of the Kemerovo Region subject to age, sex, ethnicity and smoking status were included. We formed two groups: 1) «Case» - 163 newly diagnosed lung cancer patients undergoing a medical treatment in the Kemerovo Regional Oncology Center (diagnosis «lung cancer» was determined by experienced doctors from the Kemerovo Regional Oncology based on the results of special medical examination); 2) «Control» - 175 healthy donors of the Kemerovo Regional Center of Blood Transfusion. All donors included in the research were smoking Russian men over 40 years old. The aim of this study was the comparative analysis of polymorphic variants of folate metabolism genes and chromosomal aberrations (CAs) in lung cancer patients and healthy donors resident in the same territory. The following methods were used in our investigation: 1) the routine method of lymphocytes cultivation and chromosomal aberration analysis; 2) the real-time polymerase chain reaction using TaqMan assay for a study of the MTHFR gene C677T polymorphism , the MTR gene A2756G polymorphism and the MTRR gene А66G polymorphism. Statistical analysis were performed using nonparametric statistics (Mann-Whitney U Test for paired comparison of quantitative characteristics), logistic regression (for determination of association of polymorphism in additive, dominant, overdominant, recessive and log-additive models subject to quantitative and binary characteristics), Multifactor Dimensionality Reduction method (for investigation of gene-gene interactions). It was determined that the CAs frequency (both chromatid- and chromosome-type aberrations) was significant increased in lung cancer patients compared to control group. The greatest frequency of chromosome-type aberrations was determined in lung cancer patients with the minor allelic variant (T/T and C/T) on the MTHFR gene. Carriers of such genotype are characterized by decreased functional activity of enzymes. Obtained results suggest the possible effect of failure in folate cycle to the chromosomal instability in conditions of cancerogenic load of environment.

рак легкого, гены фолатного цикла, MTHFR, MTR, MTRR, хромосомные аберрации, lung cancer, folate metabolism genes, MTHFR, MTR, MTRR, chromosomal aberrations

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