São Jose do Rio Preto Medical School (FAMERP), Molecular Biology Department, Genetic and Molecular Biology Research Unit (UPGEM), São José do Rio Preto, Brazil.
São Jose do Rio Preto Medical School (FAMERP), Otorhinolaryngology and Head and Neck Surgery Department, São José do Rio Preto, Brazil.
Asian Pac J Cancer Prev. 2020 Dec 1;21(12):3751-3759. doi: 10.31557/APJCP.2020.21.12.3751.
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.
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.
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.
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.
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.
叶酸对于 DNA 的合成、修复和甲基化至关重要。与叶酸代谢相关的基因多态性可能改变这些过程，并因此调节癌症的发展。
我们旨在评估 DNMT3B-149C/T(rs2424913)、DNMT3B-283T/C(rs6087990)、DNMT3B-579G/T(rs2424909)、DHFR 19-pb ins/del(rs70991108)、SHMT1 1420C/T(rs1979277)和 TYMS 28-bp 串联重复(rs34743033)多态性与头颈部癌症风险的关系。
在 1086 名巴西个体中进行了病例对照研究。采用实时和常规聚合酶链反应-PCR 对多态性进行基因分型。
单核苷酸多态性(SNP)DNMT3B-283T/C 与 C 组相比，在共显性(p<0.001)、显性(p<0.001)和超显性(p=0.001)模型中，T/C 和 C/C 基因型的头颈部鳞状细胞癌(HNSCC)风险更高。DNMT3B-149C/T 和 DNMT3B-579G/T 显示在任何模型中，各组之间均无关联。DHFR 19-pb ins/del 多态性与 C 组相比，通过共显性(p<0.001)、显性(p<0.001)和超显性(p<0.001)模型，对 HNSCC 发病具有保护作用。在 TYMS 中，与 C 组相比，3R/3R 基因型通过隐性模型对 HNSCC 发病具有保护作用(p=0.009)。相反，SHMT1 1420C/T 与 HNSCC 和 C 组之间无关联。DHFR 19-pb ins/del 多态性对口腔癌有保护作用(p=0.003)，只有 TYMS-28 3R/3R 降低了肿瘤进展的风险(p=0.023)。在 Kaplan-Meier 曲线中，发现 DHFR ins/ins 与 TYMS-28 3R 携带者之间存在与无复发生存时间相关的关联；此外，DNMT3B-579T 和 TYMS-28 2R/2R 携带者的存活时间更长。
DNMT3B-283T/C 与更高的风险相关，而 DHFR 19-pb ins/del 和 TYMS 28 3R/3R 则对头颈部癌症具有保护作用。我们还强调了 TYMS 3R/3R 基因型携带者与无复发生存期癌症保护和生存时间之间的关联。
