Evaluating the role of NTHL1 p.Q90* allele in inherited breast cancer predisposition.
BRCA1 Protein
/ genetics
BRCA2 Protein
/ genetics
Codon, Nonsense
Deoxyribonuclease (Pyrimidine Dimer)
/ genetics
ErbB Receptors
/ genetics
Fanconi Anemia Complementation Group N Protein
/ genetics
Gene Frequency
Genetic Predisposition to Disease
Hereditary Breast and Ovarian Cancer Syndrome
/ genetics
Heterozygote
Humans
Pedigree
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
15
06
2020
revised:
13
08
2020
accepted:
18
08
2020
pubmed:
20
9
2020
medline:
8
6
2021
entrez:
19
9
2020
Statut:
ppublish
Résumé
Rare protein truncating variants of NTHL1 gene are causative for the recently described, recessively inherited NTHL1 tumor syndrome that is characterized by an increased lifetime risk for colorectal cancer, colorectal polyposis, and breast cancer. Although there is strong evidence for breast cancer being a part of the cancer spectrum in these families, the role of pathogenic NTHL1 variants in breast cancer susceptibility in general population remains unclear. We tested the prevalence of NTHL1 nonsense variant c.268C>T, p.Q90*, which is the major allele in NTHL1 families and also shows enrichment in the Finnish population, in a total of 1333 breast cancer patients. Genotyping was performed for DNA samples extracted from peripheral blood by using high-resolution melt analysis. Sixteen NTHL1 p.Q90* heterozygous carriers were identified (1.2%, p = 0.61): 5 in hereditary cohort (n = 234, 2.1%, p = 0.39) and 11 in unselected cohort (n = 1099, 1.0%, p = 0.36). This frequency is equal to that in the general population (19/1324, 1.4%). No NTHL1 p.Q90* homozygotes were identified. Our results indicate that NTHL1 p.Q90* heterozygous carriers do not have an increased risk for breast cancer and that the variant is unlikely to be a significant contributor to breast cancer risk at the population level.
Sections du résumé
BACKGROUND
Rare protein truncating variants of NTHL1 gene are causative for the recently described, recessively inherited NTHL1 tumor syndrome that is characterized by an increased lifetime risk for colorectal cancer, colorectal polyposis, and breast cancer. Although there is strong evidence for breast cancer being a part of the cancer spectrum in these families, the role of pathogenic NTHL1 variants in breast cancer susceptibility in general population remains unclear.
METHODS
We tested the prevalence of NTHL1 nonsense variant c.268C>T, p.Q90*, which is the major allele in NTHL1 families and also shows enrichment in the Finnish population, in a total of 1333 breast cancer patients. Genotyping was performed for DNA samples extracted from peripheral blood by using high-resolution melt analysis.
RESULTS
Sixteen NTHL1 p.Q90* heterozygous carriers were identified (1.2%, p = 0.61): 5 in hereditary cohort (n = 234, 2.1%, p = 0.39) and 11 in unselected cohort (n = 1099, 1.0%, p = 0.36). This frequency is equal to that in the general population (19/1324, 1.4%). No NTHL1 p.Q90* homozygotes were identified.
CONCLUSION
Our results indicate that NTHL1 p.Q90* heterozygous carriers do not have an increased risk for breast cancer and that the variant is unlikely to be a significant contributor to breast cancer risk at the population level.
Identifiants
pubmed: 32949222
doi: 10.1002/mgg3.1493
pmc: PMC7667375
doi:
Substances chimiques
BRCA1 Protein
0
BRCA1 protein, human
0
BRCA2 Protein
0
BRCA2 protein, human
0
Codon, Nonsense
0
Fanconi Anemia Complementation Group N Protein
0
PALB2 protein, human
0
ErbB Receptors
EC 2.7.10.1
Deoxyribonuclease (Pyrimidine Dimer)
EC 3.1.25.1
NTHL1 protein, human
EC 3.1.25.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1493Informations de copyright
© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
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