ArticleNPJ breast cancer2021
Evaluation of the association of heterozygous germline variants in NTHL1 with breast cancer predisposition: an international multi-center study of 47,180 subjects.
Article in NPJ breast cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 16 citations in OpenAlex.
- Clinicopathological and molecular study of two unique cases with microglandular and acinic cell-like breast carcinoma.Histopathology · 2026Article
- Characterization of the molecular and clinical features of Multilocus Inherited Neoplasia Allelic Syndrome (MINAS) cases in the Turkish population.Familial cancer · 2026Article
- High-depth whole genome sequencing of premalignant breast lesions reveals rearrangement hotspots and personalized management opportunities.Nature communications · 2026Article
- Increased vulnerability of colorectal cancer models with high alkylation damage to NTHL1 inactivation.Scientific reports · 2026Article
- Molecular Basis of Adenomatous Gastrointestinal Polyposis Syndromes: Role of Pathogenic and Benign Variants in Disease Onset.Biomedicines · 2026Article
- Genetics, genomics and clinical features of adenomatous polyposis.Familial cancer · 2025Review
- Cohort Profile: Lifepool.International journal of epidemiology · 2025Article
- Assessment of candidate high-grade serous ovarian carcinoma predisposition genes through integrated germline and tumour sequencing.NPJ genomic medicine · 2025Article
- Non-RB1 germline cancer predisposing variants found in retinoblastoma patients.Genetics in medicine open · 2024Article
- NTHL1 is a recessive cancer susceptibility gene.Scientific reports · 2023Article
- Article
- Combined germline and tumor mutation signature testing identifies new families withFrontiers in genetics · 2023Article
- Genetic analyses of DNA repair pathway associated genes implicate new candidate cancer predisposing genes in ancestrally defined ovarian cancer cases.Frontiers in oncology · 2023Article
- How many is too many? Polyposis syndromes and what to do next.Current opinion in gastroenterology · 2022Review
- POLE, POLD1, and NTHL1: the last but not the least hereditary cancer-predisposing genes.Oncogene · 2021Review
- Evaluation of the association of heterozygous germline variants in NTHL1 with breast cancer predisposition: an international multi-center study of 47,180 subjects.NPJ breast cancer · 2021Article
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Authors and funding
33 authors at 15 institutions in 9 countries.
Funding
Abstract
Bi-allelic loss-of-function (LoF) variants in the base excision repair (BER) gene NTHL1 cause a high-risk hereditary multi-tumor syndrome that includes breast cancer, but the contribution of heterozygous variants to hereditary breast cancer is unknown. An analysis of 4985 women with breast cancer, enriched for familial features, and 4786 cancer-free women revealed significant enrichment for NTHL1 LoF variants. Immunohistochemistry confirmed reduced NTHL1 expression in tumors from heterozygous carriers but the NTHL1 bi-allelic loss characteristic mutational signature (SBS 30) was not present. The analysis was extended to 27,421 breast cancer cases and 19,759 controls from 10 international studies revealing 138 cases and 93 controls with a heterozygous LoF variant (OR 1.06, 95% CI: 0.82-1.39) and 316 cases and 179 controls with a missense variant (OR 1.31, 95% CI: 1.09-1.57). Missense variants selected for deleterious features by a number of in silico bioinformatic prediction tools or located within the endonuclease III functional domain showed a stronger association with breast cancer. Somatic sequencing of breast cancers from carriers indicated that the risk associated with NTHL1 appears to operate through haploinsufficiency, consistent with other described low-penetrance breast cancer genes. Data from this very large international multicenter study suggests that heterozygous pathogenic germline coding variants in NTHL1 may be associated with low- to moderate- increased risk of breast cancer.
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