| Abstrakt: |
The published studies of onco-associated genetic polymorphisms are characterized by insufficient interlaboratory reproducibility. The inconsistency of the results can be partially attributed to some characteristics of patients and control groups, which are used for the comparison of allele frequencies. For instance, many investigations involve so-called "healthy donors" as a standard. However, the efficiency of such a comparison can be questioned; indeed, as an individual life-time risk of malignancy reaches as high as 40-50%, a significant part of "healthy donors" would soon or later become the oncological patients. Here we tested the advantage of using "true" oncologically tolerant individuals as an additional control, e.g. tumor-free people, who succeeded to achieve an elderly age without signs of any neoplastic disease. GSTM1 gene polymorphism was used as a "positive control" for this novel design of molecular epidemiological study, as the GSTM1-null genotype displays slight but reproducible association with lung cancer risk. In the present investigation, GSTM1-deficiency was detected in 45% elderly tumor-free individuals, 55% healthy middle-aged donors, and 59% lung cancer patients. The minimal frequency (43%) of GSTM1(-) genotype was detected in elderly tumor-free smokers, and the maximal one (100%) was found in never-smoking lung cancer patients. Thus, the comparison of lung cancer patients to the "true" oncologically tolerant cohort (elderly tumor-free individuals, especially smokers) revealed more demonstrative deviations for the unfavorable genotype, than the traditional comparative analysis between oncological patients and healthy donors. |
