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

Abstract

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.

• Authors: Timo Kumpula, Anna Tervasmäki, Tuomo Mantere, Susanna Koivuluoma, Laura Huilaja, Kaisa Tasanen, Robert Winqvist, Richarda M de Voer, Katri Pylkäs
• Journal: Molecular genetics & genomic medicine (Mol Genet Genomic Med) Vol. 8 Issue 11 Pg. e1493 (11 2020) ISSN: 2324-9269 [Electronic] United States
• PMID: 32949222 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.

Chemical References

• BRCA1 Protein
• BRCA1 protein, human
• BRCA2 Protein
• BRCA2 protein, human
• Codon, Nonsense
• Fanconi Anemia Complementation Group N Protein
• PALB2 protein, human
• ErbB Receptors
• Deoxyribonuclease (Pyrimidine Dimer)
• NTHL1 protein, human

Topics

• 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