<i>NTHL1</i> Gene Mutations in Polish Polyposis Patients—Weighty Player or Vague Background?

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 <i>NTHL1</i> gene, which is involved in base ex...

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Main Authors: Natalia Grot, Marta Kaczmarek-Ryś, Emilia Lis-Tanaś, Alicja Kryszczyńska, Dorota Nowakowska, Anna Jakubiuk-Tomaszuk, Jacek Paszkowski, Tomasz Banasiewicz, Szymon Hryhorowicz, Andrzej Pławski
Format: Article
Language:English
Published: MDPI AG 2023-09-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/24/19/14548
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author Natalia Grot
Marta Kaczmarek-Ryś
Emilia Lis-Tanaś
Alicja Kryszczyńska
Dorota Nowakowska
Anna Jakubiuk-Tomaszuk
Jacek Paszkowski
Tomasz Banasiewicz
Szymon Hryhorowicz
Andrzej Pławski
author_facet Natalia Grot
Marta Kaczmarek-Ryś
Emilia Lis-Tanaś
Alicja Kryszczyńska
Dorota Nowakowska
Anna Jakubiuk-Tomaszuk
Jacek Paszkowski
Tomasz Banasiewicz
Szymon Hryhorowicz
Andrzej Pławski
author_sort Natalia Grot
collection DOAJ
description 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 <i>NTHL1</i> 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, <i>p</i> 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 <i>NTHL1</i> 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 <i>NTHL1</i> gene screening in this group reasonable.
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spelling doaj.art-af421b87a4a742259f0901c35674abd82023-11-19T14:28:21ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124191454810.3390/ijms241914548<i>NTHL1</i> Gene Mutations in Polish Polyposis Patients—Weighty Player or Vague Background?Natalia Grot0Marta Kaczmarek-Ryś1Emilia Lis-Tanaś2Alicja Kryszczyńska3Dorota Nowakowska4Anna Jakubiuk-Tomaszuk5Jacek Paszkowski6Tomasz Banasiewicz7Szymon Hryhorowicz8Andrzej Pławski9Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479 Poznań, PolandInstitute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479 Poznań, PolandInstitute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479 Poznań, PolandInstitute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479 Poznań, PolandCancer Genetics Unit, Cancer Prevention Department, The Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, 02-781 Warsaw, PolandDepartment of Pediatric Neurology, Medical University of Bialystok, 15-089 Bialystok, PolandDepartment of General and Endocrine Surgery and Gastroenterological Oncology, Poznań University of Medical Sciences, Przybyszewskiego 49, 60-355 Poznań, PolandDepartment of General and Endocrine Surgery and Gastroenterological Oncology, Poznań University of Medical Sciences, Przybyszewskiego 49, 60-355 Poznań, PolandInstitute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479 Poznań, PolandInstitute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479 Poznań, PolandMultiple 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 <i>NTHL1</i> 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, <i>p</i> 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 <i>NTHL1</i> 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 <i>NTHL1</i> gene screening in this group reasonable.https://www.mdpi.com/1422-0067/24/19/14548colon polyposisCRCFAP<i>NTHL1</i> gene
spellingShingle Natalia Grot
Marta Kaczmarek-Ryś
Emilia Lis-Tanaś
Alicja Kryszczyńska
Dorota Nowakowska
Anna Jakubiuk-Tomaszuk
Jacek Paszkowski
Tomasz Banasiewicz
Szymon Hryhorowicz
Andrzej Pławski
<i>NTHL1</i> Gene Mutations in Polish Polyposis Patients—Weighty Player or Vague Background?
International Journal of Molecular Sciences
colon polyposis
CRC
FAP
<i>NTHL1</i> gene
title <i>NTHL1</i> Gene Mutations in Polish Polyposis Patients—Weighty Player or Vague Background?
title_full <i>NTHL1</i> Gene Mutations in Polish Polyposis Patients—Weighty Player or Vague Background?
title_fullStr <i>NTHL1</i> Gene Mutations in Polish Polyposis Patients—Weighty Player or Vague Background?
title_full_unstemmed <i>NTHL1</i> Gene Mutations in Polish Polyposis Patients—Weighty Player or Vague Background?
title_short <i>NTHL1</i> Gene Mutations in Polish Polyposis Patients—Weighty Player or Vague Background?
title_sort i nthl1 i gene mutations in polish polyposis patients weighty player or vague background
topic colon polyposis
CRC
FAP
<i>NTHL1</i> gene
url https://www.mdpi.com/1422-0067/24/19/14548
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