| Summary: | The development of individual medicine is a very important part of the whole health care system and especially of the oncology patients’ treatment. The predictive markers could help to prevent the development of the different diseases. Individual risk assessment is based on the study of polymorphisms in genes specific to different pathologies, especially those with a significant social impact, such as lung cancer.
Like many other cancers, lung cancer is a multi-factorial disease. The tumor suppressor genes are important in its pathogenesis. One such very important gene is TP53, which encodes the p53 tumor suppressor protein. It regulates the activation of specific cellular processes and signaling pathways involved in regulation, recognition of signals inside the cell, coordination of metabolic processes, genome repair, cell division and death (apoptosis), and interactions between cells. Insufficient production or property modification of this protein leads to the development of serious diseases, including lung cancer.
The TP53 gene has a number of polymorphic markers; the Arg72Pro and the Gln157Lys markers are very important in case of lung cancer. They are located in the DNA-binding domain of TP53 at exons that play essential structural and chemical roles in the contact between the p53 protein and specific DNA sequences that constitute the p53 response elements. These mutations result in a significant loss of DNA-binding activity and transactivation capacity (P. Hainaut and M. Hollstein, 2000).
We studied the association of polymorphic markers Arg72Pro and Gln157Lys of TP53 gene with the risk of nonsmall cell lung cancer (NSCLC) in patients from the Moscow region. Our study included 88 patients with NSCLC, 160 healthy persons as a control for Arg72Pro and 60 healthy persons as a control for Gln157Lys. We used PCR-RLFP analysis to identify the alleles of the polymorphic markers.
We observed higher frequencies of the markers predisposition genotypes in group of patients then in control group. The distribution frequency of Pro/Pro genotype Arg72Pro marker was 0.307 in the group of patients and 0.075 in the control. For the Gln157Lys marker the Lys/Lys genotype was not observed. The frequency of Gln/Lys genotype Gln157Lys marker was 0.377 in patients and 0.106 in the control. We found the association of both markers with the risk of NSCLC development. The genotype Pro/Pro of Arg72Pro marker showed the increasing of NSCLC risk: OR = 5.46, p = 8 × 10−6. The presence of Gln/Lys genotype of Gln157Lys marker also led to increased risk of cancer development: OR = 5.10, p = 0.002.
Our results suggest the importance of studied polymorphic markers for risk of NSCLC assessment. The status of the Arg72Pro and the Gln157Lys markers of TP53 gene can serve as an independent prognostic indicator in this type of cancer.
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