Cargando…

DNA Mismatch Repair Gene Variants in Sporadic Solid Cancers

The phenotypic effects of single nucleotide polymorphisms (SNPs) in the development of sporadic solid cancers are still scarce. The aim of this review was to summarise and analyse published data on the associations between SNPs in mismatch repair genes and various cancers. The mismatch repair system...

Descripción completa

Detalles Bibliográficos
Autores principales: Caja, Fabian, Vodickova, Ludmila, Kral, Jan, Vymetalkova, Veronika, Naccarati, Alessio, Vodicka, Pavel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432688/
https://www.ncbi.nlm.nih.gov/pubmed/32756484
http://dx.doi.org/10.3390/ijms21155561
_version_ 1783571852045582336
author Caja, Fabian
Vodickova, Ludmila
Kral, Jan
Vymetalkova, Veronika
Naccarati, Alessio
Vodicka, Pavel
author_facet Caja, Fabian
Vodickova, Ludmila
Kral, Jan
Vymetalkova, Veronika
Naccarati, Alessio
Vodicka, Pavel
author_sort Caja, Fabian
collection PubMed
description The phenotypic effects of single nucleotide polymorphisms (SNPs) in the development of sporadic solid cancers are still scarce. The aim of this review was to summarise and analyse published data on the associations between SNPs in mismatch repair genes and various cancers. The mismatch repair system plays a unique role in the control of the genetic integrity and it is often inactivated (germline and somatic mutations and hypermethylation) in cancer patients. Here, we focused on germline variants in mismatch repair genes and found the outcomes rather controversial: some SNPs are sometimes ascribed as protective, while other studies reported their pathological effects. Regarding the complexity of cancer as one disease, we attempted to ascertain if particular polymorphisms exert the effect in the same direction in the development and treatment of different malignancies, although it is still not straightforward to conclude whether polymorphisms always play a clear positive role or a negative one. Most recent and robust genome-wide studies suggest that risk of cancer is modulated by variants in mismatch repair genes, for example in colorectal cancer. Our study shows that rs1800734 in MLH1 or rs2303428 in MSH2 may influence the development of different malignancies. The lack of functional studies on many DNA mismatch repair SNPs as well as their interactions are not explored yet. Notably, the concerted action of more variants in one individual may be protective or harmful. Further, complex interactions of DNA mismatch repair variations with both the environment and microenvironment in the cancer pathogenesis will deserve further attention.
format Online
Article
Text
id pubmed-7432688
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-74326882020-08-27 DNA Mismatch Repair Gene Variants in Sporadic Solid Cancers Caja, Fabian Vodickova, Ludmila Kral, Jan Vymetalkova, Veronika Naccarati, Alessio Vodicka, Pavel Int J Mol Sci Review The phenotypic effects of single nucleotide polymorphisms (SNPs) in the development of sporadic solid cancers are still scarce. The aim of this review was to summarise and analyse published data on the associations between SNPs in mismatch repair genes and various cancers. The mismatch repair system plays a unique role in the control of the genetic integrity and it is often inactivated (germline and somatic mutations and hypermethylation) in cancer patients. Here, we focused on germline variants in mismatch repair genes and found the outcomes rather controversial: some SNPs are sometimes ascribed as protective, while other studies reported their pathological effects. Regarding the complexity of cancer as one disease, we attempted to ascertain if particular polymorphisms exert the effect in the same direction in the development and treatment of different malignancies, although it is still not straightforward to conclude whether polymorphisms always play a clear positive role or a negative one. Most recent and robust genome-wide studies suggest that risk of cancer is modulated by variants in mismatch repair genes, for example in colorectal cancer. Our study shows that rs1800734 in MLH1 or rs2303428 in MSH2 may influence the development of different malignancies. The lack of functional studies on many DNA mismatch repair SNPs as well as their interactions are not explored yet. Notably, the concerted action of more variants in one individual may be protective or harmful. Further, complex interactions of DNA mismatch repair variations with both the environment and microenvironment in the cancer pathogenesis will deserve further attention. MDPI 2020-08-03 /pmc/articles/PMC7432688/ /pubmed/32756484 http://dx.doi.org/10.3390/ijms21155561 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Caja, Fabian
Vodickova, Ludmila
Kral, Jan
Vymetalkova, Veronika
Naccarati, Alessio
Vodicka, Pavel
DNA Mismatch Repair Gene Variants in Sporadic Solid Cancers
title DNA Mismatch Repair Gene Variants in Sporadic Solid Cancers
title_full DNA Mismatch Repair Gene Variants in Sporadic Solid Cancers
title_fullStr DNA Mismatch Repair Gene Variants in Sporadic Solid Cancers
title_full_unstemmed DNA Mismatch Repair Gene Variants in Sporadic Solid Cancers
title_short DNA Mismatch Repair Gene Variants in Sporadic Solid Cancers
title_sort dna mismatch repair gene variants in sporadic solid cancers
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432688/
https://www.ncbi.nlm.nih.gov/pubmed/32756484
http://dx.doi.org/10.3390/ijms21155561
work_keys_str_mv AT cajafabian dnamismatchrepairgenevariantsinsporadicsolidcancers
AT vodickovaludmila dnamismatchrepairgenevariantsinsporadicsolidcancers
AT kraljan dnamismatchrepairgenevariantsinsporadicsolidcancers
AT vymetalkovaveronika dnamismatchrepairgenevariantsinsporadicsolidcancers
AT naccaratialessio dnamismatchrepairgenevariantsinsporadicsolidcancers
AT vodickapavel dnamismatchrepairgenevariantsinsporadicsolidcancers