Journal Article Epublish 6 citations
PubMed: 38036545 DOI: 10.1038/s41598-023-47441-w
NTHL1 is a recessive cancer susceptibility gene.
Sci Rep 13(1):21127
Authors: Anna K Nurmi, Liisa M Pelttari, Johanna I Kiiski, Sofia Khan, Mika Nurmikolu, Maija Suvanto, Niina Aho, Tiina Tasmuth, Eija Kalso, Johanna Schleutker, Anne Kallioniemi, Päivi Heikkilä, Kristiina Aittomäki, Carl Blomqvist, Heli Nevanlinna
Affiliations
- Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Biomedicum Helsinki, P.O. Box 700, 00290, Helsinki, Finland.
- Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
- Institute of Biomedicine, University of Turku, and FICAN West Cancer Centre, and Department of Genomics, Laboratory Division, Turku University Hospital, Turku, Finland.
- Tays Cancer Center, Tampere University Hospital, and BioMediTech Institute and Faculty of Medicine and Health Technology, Tampere University, and Fimlab Laboratories, Tampere, Finland.
- Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
- Department of Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
- Department of Oncology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
- Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Biomedicum Helsinki, P.O. Box 700, 00290, Helsinki, Finland.
Abstract
In search of novel breast cancer (BC) risk variants, we performed a whole-exome sequencing and variant analysis of 69 Finnish BC patients as well as analysed loss-of-function variants identified in DNA repair genes in the Finns from the Genome Aggregation Database. Additionally, we carried out a validation study of SERPINA3 c.918-1G>C, recently suggested for BC predisposition. We estimated the frequencies of 41 rare candidate variants in 38 genes by genotyping them in 2482-4101 BC patients and in 1273-3985 controls. We further evaluated all coding variants in the candidate genes in a dataset of 18,786 BC patients and 182,927 controls from FinnGen. None of the variants associated significantly with cancer risk in the primary BC series; however, in the FinnGen data, NTHL1 c.244C>T p.(Gln82Ter) associated with BC with a high risk for homozygous (OR = 44.7 [95% CI 6.90-290], P = 6.7 × 10) and a low risk for heterozygous women (OR = 1.39 [1.18-1.64], P = 7.8 × 10). Furthermore, the results suggested a high risk of colorectal, urinary tract, and basal-cell skin cancer for homozygous individuals, supporting NTHL1 as a recessive multi-tumour susceptibility gene. No significant association with BC risk was detected for SERPINA3 or any other evaluated gene.
MeSH
Genes, Neoplasms