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. 2023 Sep 26;24(19):14548.
doi: 10.3390/ijms241914548.

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

Natalia Grot  1 , Marta Kaczmarek-Ryś  1 , Emilia Lis-Tanaś  1 , Alicja Kryszczyńska  1 , Dorota Nowakowska  2 , Anna Jakubiuk-Tomaszuk  3   4 , Jacek Paszkowski  5 , Tomasz Banasiewicz  5 , Szymon Hryhorowicz  1 , Andrzej Pławski  1   5
Affiliations

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

Natalia Grot et al. Int J Mol Sci. .

Abstract

Multiple polyposes are heterogeneous diseases with different underlying molecular backgrounds, sharing a common symptom: the presence of transforming into cancerous intestinal polyps. Recent reports have indicated biallelic mutations in the NTHL1 gene, which is involved in base excision repair (BER), as predisposing to an elevated risk of colorectal cancer (CRC). We aimed to evaluate the significance of the p.Q82* truncating variant in predisposition to intestinal polyposis by assessing its frequency in polyposis patients. We genotyped 644 Polish patients and 634 control DNA samples using high-resolution melting analysis (HRM) and Sanger sequencing. We found the p.Q82* variant in four polyposis patients; in three, it was homozygous (OR = 6.90, p value = 0.202). Moreover, the p.R92C mutation was detected in one patient. We also looked more closely at the disease course in patients carrying NTHL1 mutations. Two homozygous patients also presented other neoplasia. In the family case, we noticed the earlier presence of polyps in the proband and early hepatoblastoma in his brother. We cannot univocally confirm the relationship of p.Q82* with an increased risk of CRC. However, homozygous p.Q82* was more frequent by 10-fold in patients without other mutations identified, which makes NTHL1 gene screening in this group reasonable.

Keywords: CRC; FAP; NTHL1 gene; colon polyposis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Main polyposis syndromes with genetic background.
Figure 2
Figure 2
Family tree of C3003 patient. Proband was diagnosed with polyposis: APC c.2413C>T and NTHL1 c.244C>T. Family interview and mutation screening of the family members was conducted, n.a.—not available.
See this image and copyright information in PMC

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