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

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• Folate is crucial for DNA synthesis, repair, and methylation.
• Genetic variations (polymorphisms) in folate metabolism genes can influence these processes and cancer development.

Purpose of the Study:

• To investigate the association between specific gene polymorphisms (DNMT3B, DHFR, SHMT1, TYMS) and the risk of head and neck cancer.
• To evaluate the impact of these polymorphisms on cancer development and progression.

Main Methods:

• A case-control study involving 1,086 Brazilian participants.
• Genotyping of polymorphisms using real-time and conventional polymerase chain reaction (PCR).

Main Results:

• The DNMT3B -283T/C polymorphism was linked to an increased risk of head and neck squamous cell carcinoma (HNSCC).
• DHFR 19-pb ins/del and TYMS 28 3R/3R genotypes demonstrated a protective effect against HNSCC.
• DHFR 19-pb ins/del also protected against oral cavity cancer, and TYMS 3R/3R reduced tumor progression risk.
• Specific genotypes (DHFR ins/ins, TYMS -28 3R) were associated with improved relapse-free survival, while DNMT3B -579 T and TYMS-28 2R/2R carriers showed longer survival times.

Conclusions:

• DNMT3B -283T/C is a risk factor for head and neck cancer.
• DHFR 19-pb ins/del and TYMS 28 3R/3R genotypes are protective against head and neck cancer.
• TYMS 3R/3R genotype is associated with improved relapse-free survival and overall survival in head and neck cancer patients.