Gene Polymorphisms Involved in Folate Metabolism and DNA Methylation with the Risk of Head and Neck Cancer.

Autor: De Castro TB; São Jose do Rio Preto Medical School (FAMERP), Molecular Biology Department, Genetic and Molecular Biology Research Unit (UPGEM), São José do Rio Preto, Brazil., Rodrigues-Fleming GH; São Jose do Rio Preto Medical School (FAMERP), Molecular Biology Department, Genetic and Molecular Biology Research Unit (UPGEM), São José do Rio Preto, Brazil., Oliveira-Cucolo JG; São Jose do Rio Preto Medical School (FAMERP), Molecular Biology Department, Genetic and Molecular Biology Research Unit (UPGEM), São José do Rio Preto, Brazil., Silva JNGD; São Jose do Rio Preto Medical School (FAMERP), Molecular Biology Department, Genetic and Molecular Biology Research Unit (UPGEM), São José do Rio Preto, Brazil., Silva FP; São Jose do Rio Preto Medical School (FAMERP), Molecular Biology Department, Genetic and Molecular Biology Research Unit (UPGEM), São José do Rio Preto, Brazil., Raposo LS; São Jose do Rio Preto Medical School (FAMERP), Otorhinolaryngology and Head and Neck Surgery Department, São José do Rio Preto, Brazil., Maniglia JV; São Jose do Rio Preto Medical School (FAMERP), Otorhinolaryngology and Head and Neck Surgery Department, São José do Rio Preto, Brazil., Pavarino EC; São Jose do Rio Preto Medical School (FAMERP), Molecular Biology Department, Genetic and Molecular Biology Research Unit (UPGEM), São José do Rio Preto, Brazil., Batista Arantes LMR; São Jose do Rio Preto Medical School (FAMERP), Molecular Biology Department, Genetic and Molecular Biology Research Unit (UPGEM), São José do Rio Preto, Brazil., Galbiatti-Dias ALS; São Jose do Rio Preto Medical School (FAMERP), Molecular Biology Department, Genetic and Molecular Biology Research Unit (UPGEM), São José do Rio Preto, Brazil., Maria Goloni Bertollo E; São Jose do Rio Preto Medical School (FAMERP), Molecular Biology Department, Genetic and Molecular Biology Research Unit (UPGEM), São José do Rio Preto, Brazil.
Jazyk: angličtina
Zdroj: Asian Pacific journal of cancer prevention : APJCP [Asian Pac J Cancer Prev] 2020 Dec 01; Vol. 21 (12), pp. 3751-3759. Date of Electronic Publication: 2020 Dec 01.
DOI: 10.31557/APJCP.2020.21.12.3751
Abstrakt: Background: Folate is essential for DNA synthesis, repair, and methylation. Polymorphisms in genes associated with folate metabolism may alter these processes and, consequently, modulate cancer development.
Aim: We aimed to assess DNMT3B -149C/T (rs2424913), DNMT3B -283T/C (rs6087990), DNMT3B -579G/T (rs2424909), DHFR 19-pb ins/del (rs70991108), SHMT1 1420C/T (rs1979277), and TYMS 28-bp tandem repeat (rs34743033) polymorphisms with risk of head and neck cancer.
Methods: A case-control study was conducted in 1,086 Brazilian individuals. Real-time and conventional polymerase chain reactions-PCR were performed for genotyping the polymorphisms.
Results: The single nucleotide polymorphism (SNP), DNMT3B -283T/C, revealed a higher risk of head and neck squamous cell carcinoma (HNSCC) when compared with the C group in the codominant (p < 0.001), dominant (p <0.001), and overdominant (p= 0.001) models for T/C and C/C genotypes. DNMT3B -149C/T and DNMT3B -579G/T revealed no association between groups in any model. The DHFR 19-pb ins/del polymorphism protected against HNSCC development compared to the C group by the codominant (p < 0.001), dominant (p < 0.001), and overdominant (p < 0.001) models. In the TYMS, the 3R/3R genotype had a protective effect against HNSCC development compared with the C group by the recessive models (p= 0.009). In contrast, SHMT1 1420 C/T presented no association between the HNSCC and C groups. DHFR 19-pb ins/del polymorphisms protected against oral cavity cancer (p= 0.003), and only TYMS-28 3R/3R decreased the risk of tumor progression (p= 0.023). In the Kaplan-Meier curve, an association was found between DHFR ins/ins and TYMS -28 3R carriers with respect to relapse-free time; further, DNMT3B -579 T and TYMS-28 2R/2R carriers had longer survival times.
Conclusion: DNMT3B -283T/C is associated with higher risk, whereas DHFR 19-pb ins/del and TYMS 28 3R/3R protect against head and neck cancer. We also highlighted the association of TYMS 3R/3R genotype carriers with relapse-free cancer protection and survival time.
Databáze: MEDLINE