University of Oulu

How to cite this article: Kumpula T, Tervasmäki A, Mantere T, et al. Evaluating the role of NTHL1 p.Q90* allele in inherited breast cancer predisposition. Molecular Genetics & Genomic Medicine. 2020; 8:e1493.

Evaluating the role of NTHL1 p.Q90* allele in inherited breast cancer predisposition

Saved in:
Author: Kumpula, Timo1; Tervasmäki, Anna1; Mantere, Tuomo1,2;
Organizations: 1Laboratory of Cancer Genetics and Tumor Biology, University of Oulu, Oulu, Finland
2Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
3Department of Dermatology and Medical Research Center Oulu, PEDEGO Research Unit, University of Oulu, Oulu University Hospital, Oulu, Finland
4Department of Human Genetics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.3 MB)
Persistent link:
Language: English
Published: John Wiley & Sons, 2020
Publish Date: 2021-02-10


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.

see all

Series: Molecular genetics & genomic medicine
ISSN: 2324-9269
ISSN-E: 2324-9269
ISSN-L: 2324-9269
Volume: 8
Issue: 11
Article number: e1493
DOI: 10.1002/mgg3.1493
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: This work was supported by the Academy of Finland (grant numbers 307808, 314183), the Cancer Foundation of Finland sr, and Sigrid Jusélius foundation.
Academy of Finland Grant Number: 307808
Detailed Information: 307808 (Academy of Finland Funding decision)
314183 (Academy of Finland Funding decision)
Copyright information: © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.