NTHL1 Gene Mutations in Polish Polyposis Patients-Weighty Player or Vague Background?

Area of Science:

• Genetics
• Molecular Biology
• Oncology

Background:

• Multiple polyposis diseases share a common symptom: cancerous intestinal polyps.
• Biallelic mutations in the NTHL1 gene, involved in base excision repair (BER), are linked to colorectal cancer (CRC) risk.
• The p.Q82* variant in NTHL1 warrants investigation for its role in intestinal polyposis.

Purpose of the Study:

• To evaluate the significance of the NTHL1 p.Q82* variant in predisposition to intestinal polyposis.
• To assess the frequency of the p.Q82* variant in Polish polyposis patients and controls.
• To explore the clinical course of patients with NTHL1 mutations.

Main Methods:

• Genotyping of 644 Polish polyposis patients and 634 controls.
• High-resolution melting analysis (HRM) and Sanger sequencing were employed.
• Analysis included variant frequency, odds ratio (OR), and p-values.

Main Results:

• The p.Q82* variant was found in four polyposis patients, with three being homozygous (OR = 6.90, p=0.202).
• The p.R92C mutation was detected in one patient.
• Homozygous p.Q82* was 10-fold more frequent in patients lacking other identified mutations.

Conclusions:

• The direct link between NTHL1 p.Q82* and increased CRC risk is not definitively confirmed.
• NTHL1 gene screening is suggested for patients with polyposis, especially those without other identified mutations.
• Further research is needed to fully elucidate the role of NTHL1 variants in polyposis and associated cancers.