Abstract
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.
Highlights
Head and neck cancer is considered the fifth most common type of cancer worldwide and is associated with a high mortality rate when diagnosed in advanced stages
We found that the sociodemographic characteristics and risk factors indicated that the male gender, advanced age, smoking, and alcohol consumption were associated with greater susceptibility to cancer development when compared to the control group
Excessive consumption of carcinogens can affect nutrient absorption by the intestine, causing major nutritional deficiencies, and can modify the metabolic pathways, such as that of folate, which is essential for purine and pyrimidine synthesis and DNA methylation (Rettig and D’Souza, 2015)
Summary
Head and neck cancer is considered the fifth most common type of cancer worldwide and is associated with a high mortality rate when diagnosed in advanced stages. In 2020, 834,860 new cases of this neoplasm were estimated (IARC, 2019) This cancer comprises a heterogeneous group of tumors that originate in lining epithelium squamous cells of the upper digestive tract, including the lip, oral cavity, nasal cavity, paranasal sinus, pharynx, and larynx (Chow, 2020). 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
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