Single-Nucleotide Polymorphisms of the MSH2 and MLH1 Genes, Potential Molecular Markers for Susceptibility to the Development of Basal Cell Carcinoma in the Brazilian Population
Basal cell carcinoma - BCC is considered a multifactorial neoplasm involving genetic, epigenetic and environmental factors. Where UVB radiation is considered the main physical agent involved in BCC carcinogenesis. The Brazil and state of Paraíba are exposed to high levels of UVB rays. The mismatch repair - MMR is important DNA repair mechanisms to maintain replication fidelity. Therefore, single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in MMR may be potential molecular markers of susceptibility to BCC. The objective of this study was to evaluate and describe for the first time the SNPs rs560246973, rs2303425 and rs565410865 and risk of developing BCC. The present study analyzed 100 samples of paraffin-embedded tissue from patients with histopathological diagnosis of BCC and 100 control samples. The results were obtained by genotyping method, Dideoxy Unique Allele Specific – PCR (DSASP). The SNPs rs2303425 were not associated with Basal Cell Carcinoma. However, the SNPs rs560246973 and rs565410865 was shown to be associated with the development of BCC when compared to control samples (P < 0.0001). The SNPs rs565410865 was also statistical significance between the genotypes of and the age group (p = 0.0027) and tumor location (p = 0,0191). The result suggests that SNPs rs2303425 and rs565410865 are associated with susceptibility to the development of BCC in the Brazilian population and may be considered as potential molecular markers for BCC.
KeywordsBasal cell carcinoma Mismatch repair Single nucleotide polymorphism DSASP Genotyping Molecular markers
The authors would like to thank Jimmy Johnson for proofreading the article.
Compliance with Ethical Standards
Conflict of Interest
This work was supported by grants of CAPES, CNPq and Clinica Dermatológica Santa Catarina; João Pessoa - PB – Brasil.
The present study is part of the thematic project approved by the Ethics Committee of the University Hospital Lauro Wanderley - UFPB under the code CAAE: 36,522,614.2.3001.5883.
- 5.Zink BS (2014) Câncer de pele: a importância do seu diagnóstico, tratamento e prevenção Revista HUPE 13:76–83Google Scholar
- 10.Reyes GX, Schmidt TT, Kolodner RD et al (2015) New insights into the mechanism of DNA mismatch repair. Chromosoma. doi: 10.1007/s00412-015-0514-0
- 11.Smith CE, Mendillo ML, Bowen N et al (2013) Dominant mutations in S. cerevisiae PMS1 identify the Mlh1-Pms1 endonuclease active site and an exonuclease 1-independent mismatch repair pathway. PLoS Genet. doi: 10.1371/journal.pgen.1003869
- 19.Smith TR, Levine EA, Freimanis RI et al (2008) Polygenic model of DNA repair genetic polymorphisms in human breast cancer risk. Carcinogenesis. doi: 10.1093/carcin/bgn193
- 22.Nishi R, Okuda Y, Watanabe E et al (2005) Centrin 2 stimulates nucleotide excision repair by interacting with Xeroderma Pigmentosum group C protein. Mol Cell Biol. doi: 10.1128/MCB.25.13.5664-5674
- 24.Birch-Johansen F, Jensen A, Mortensen L et al (2010) Trends in the incidence of nonmelanoma skin cancer in Denmark 1978–2007: rapid incidence increase among young Danish women. Int J Cancer. doi: 10.1002/ijc.25411
- 25.Smolarz B, Makowska M, Samulak D et al (2015) Gly322Asp and Asn127Ser single nucleotide polymorphisms (SNPs) of hMSH2 mismatch repair gene and the risk of triple-negative breast cancer in polish women. Familial Cancer. doi: 10.1007/s10689-014-9746-z
- 27.Hsieh YC, Cho EC, Tu SH et al (2017) MSH2 rs2303425 polymorphism is associated with early-onset breast cancer in Taiwan. Ann Surg Oncol. doi: 10.1245/s10434-016-5168-5
- 28.Dahlman-Wright K, Qiao Y, Jonsson P et al (2012) Interplay between AP-1 and estrogen receptor α in regulating gene expression and proliferation networks in breast cancer cells. Carcinogenesis. doi: 10.1093/carcin/bgs223
- 31.van der Klift HM, Jansen AM, van der Steenstraten N et al (2015) Splicing analysis for exonic and intronic mismatch repair gene variants associated with lynch syndrome confirms high concordance between minigene assays and patient RNA analyses. Mol Genet Genomic Med. doi: 10.1002/mgg3.145
- 32.Wibom C, Sjöström S, Henriksson R et al (2012) DNA-repair gene variants are associated with glioblastoma survival. Acta Oncol. doi: 10.3109/0284186X.2011.616284
- 34.Zahary MN, Kaur G, Abu Hassan MR et al (2012) Germline mutation analysis of MLH1 and MSH2 in malaysian lynch syndrome patients. World J Gastroenterol. doi: 10.3748/wjg.v18.i8.814
- 35.Langeberg WJ, Kwon EM, Koopmeiners JS et al (2010) Population-based study of the association of variants in mismatch repair genes with prostate cancer risk and outcomes. Cancer Epidemiol Biomark Prev. doi: 10.1158/1055-9965.EPI-09-0800