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Assessment of the Role of Selected SMAD3 and SMAD4 Genes Polymorphisms in the Development of Colorectal Cancer: Preliminary Research

BACKGROUND: Colon cancer is one of the most common types of malignant tumor worldwide. The molecular mechanism of colorectal carcinogenesis is very complex and not yet fully understood. The TGFβ (transforming growth factor β) signaling pathway plays a significant role in the development of many canc...

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Autores principales: Wosiak, Agnieszka, Wodziński, Damian, Michalska, Katarzyna, Pietrzak, Jacek, Kordek, Radzisław, Balcerczak, Ewa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853629/
https://www.ncbi.nlm.nih.gov/pubmed/33542644
http://dx.doi.org/10.2147/PGPM.S281958
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author Wosiak, Agnieszka
Wodziński, Damian
Michalska, Katarzyna
Pietrzak, Jacek
Kordek, Radzisław
Balcerczak, Ewa
author_facet Wosiak, Agnieszka
Wodziński, Damian
Michalska, Katarzyna
Pietrzak, Jacek
Kordek, Radzisław
Balcerczak, Ewa
author_sort Wosiak, Agnieszka
collection PubMed
description BACKGROUND: Colon cancer is one of the most common types of malignant tumor worldwide. The molecular mechanism of colorectal carcinogenesis is very complex and not yet fully understood. The TGFβ (transforming growth factor β) signaling pathway plays a significant role in the development of many cancers, including colorectal cancer pathogenesis. Changes in TGFβ pathway are associated with increased colorectal cancer risk, because this pathway participates in the control of important cellular processes such as cell growth, proliferation, differentiation, or apoptosis. The family of SMAD (similar to mother against decapentaplegic) proteins is closely correlated to this pathway. SMADs genes expression affects modulation of the transcription of many genes, which leads to the inhibition of cell-growth and apoptosis in colon epithelial cells. The presence of SNPs (single nucleotide polymorphisms) in SMADs genes encoding proteins involved in the control of biological processes important for the cell may play a significant role in the predisposition to the development of colorectal cancer, or in the regulation of the severity of changes related to tumor growth. Extension of data in this field may provide clinically significant conclusions influencing the implementation of personalized treatment based on specific changes characteristic of a patient with colorectal cancer. PURPOSE: The subject of this research was genotyping polymorphisms of SMAD3 (rs6494629) and SMAD4 (rs10502913, rs12968012, rs1057520801) genes in the group of patients with colorectal cancer and in the control group, and comparing the genotypic frequency distributions with clinical-pathological features within the study group and between the groups. MATERIALS AND METHODS: SNP genotyping analysis was performed on genomic DNA isolated from 84 frozen tissue sections of colorectal cancer and from 60 peripheral blood samples of patients without cancer. To evaluate the polymorphic variants of SMAD genes, the restricted fragment length of a polymorphism reaction (PCR-RFLP) was used. RESULTS: The results obtained in the study showed no significant association between the examined polymorphisms and the risk of developing colorectal cancer. CONCLUSION: More extensive studies to confirm the results obtained in this study are needed. Further studies on a larger study group divided according to the clinical stage and histological differentiation may allow finding or excluding the significance of the studied SNPs as potential markers of colorectal cancer in relation to the clinico-pathological data.
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spelling pubmed-78536292021-02-03 Assessment of the Role of Selected SMAD3 and SMAD4 Genes Polymorphisms in the Development of Colorectal Cancer: Preliminary Research Wosiak, Agnieszka Wodziński, Damian Michalska, Katarzyna Pietrzak, Jacek Kordek, Radzisław Balcerczak, Ewa Pharmgenomics Pers Med Original Research BACKGROUND: Colon cancer is one of the most common types of malignant tumor worldwide. The molecular mechanism of colorectal carcinogenesis is very complex and not yet fully understood. The TGFβ (transforming growth factor β) signaling pathway plays a significant role in the development of many cancers, including colorectal cancer pathogenesis. Changes in TGFβ pathway are associated with increased colorectal cancer risk, because this pathway participates in the control of important cellular processes such as cell growth, proliferation, differentiation, or apoptosis. The family of SMAD (similar to mother against decapentaplegic) proteins is closely correlated to this pathway. SMADs genes expression affects modulation of the transcription of many genes, which leads to the inhibition of cell-growth and apoptosis in colon epithelial cells. The presence of SNPs (single nucleotide polymorphisms) in SMADs genes encoding proteins involved in the control of biological processes important for the cell may play a significant role in the predisposition to the development of colorectal cancer, or in the regulation of the severity of changes related to tumor growth. Extension of data in this field may provide clinically significant conclusions influencing the implementation of personalized treatment based on specific changes characteristic of a patient with colorectal cancer. PURPOSE: The subject of this research was genotyping polymorphisms of SMAD3 (rs6494629) and SMAD4 (rs10502913, rs12968012, rs1057520801) genes in the group of patients with colorectal cancer and in the control group, and comparing the genotypic frequency distributions with clinical-pathological features within the study group and between the groups. MATERIALS AND METHODS: SNP genotyping analysis was performed on genomic DNA isolated from 84 frozen tissue sections of colorectal cancer and from 60 peripheral blood samples of patients without cancer. To evaluate the polymorphic variants of SMAD genes, the restricted fragment length of a polymorphism reaction (PCR-RFLP) was used. RESULTS: The results obtained in the study showed no significant association between the examined polymorphisms and the risk of developing colorectal cancer. CONCLUSION: More extensive studies to confirm the results obtained in this study are needed. Further studies on a larger study group divided according to the clinical stage and histological differentiation may allow finding or excluding the significance of the studied SNPs as potential markers of colorectal cancer in relation to the clinico-pathological data. Dove 2021-01-29 /pmc/articles/PMC7853629/ /pubmed/33542644 http://dx.doi.org/10.2147/PGPM.S281958 Text en © 2021 Wosiak et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Wosiak, Agnieszka
Wodziński, Damian
Michalska, Katarzyna
Pietrzak, Jacek
Kordek, Radzisław
Balcerczak, Ewa
Assessment of the Role of Selected SMAD3 and SMAD4 Genes Polymorphisms in the Development of Colorectal Cancer: Preliminary Research
title Assessment of the Role of Selected SMAD3 and SMAD4 Genes Polymorphisms in the Development of Colorectal Cancer: Preliminary Research
title_full Assessment of the Role of Selected SMAD3 and SMAD4 Genes Polymorphisms in the Development of Colorectal Cancer: Preliminary Research
title_fullStr Assessment of the Role of Selected SMAD3 and SMAD4 Genes Polymorphisms in the Development of Colorectal Cancer: Preliminary Research
title_full_unstemmed Assessment of the Role of Selected SMAD3 and SMAD4 Genes Polymorphisms in the Development of Colorectal Cancer: Preliminary Research
title_short Assessment of the Role of Selected SMAD3 and SMAD4 Genes Polymorphisms in the Development of Colorectal Cancer: Preliminary Research
title_sort assessment of the role of selected smad3 and smad4 genes polymorphisms in the development of colorectal cancer: preliminary research
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853629/
https://www.ncbi.nlm.nih.gov/pubmed/33542644
http://dx.doi.org/10.2147/PGPM.S281958
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