A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä

NTHL1 is a recessive cancer susceptibility gene




TekijätNurmi Anna K., Pelttari Liisa M., Kiiski Johanna I., Khan Sofia, Nurmikolu Mika, Suvanto Maija, Aho Niina, Tasmuth Tiina, Kalso Eija, Schleutker Johanna, Kallioniemi Anne, Heikkilä Päivi; FinnGen, Aittomäki Kristiina, Blomqvist Carl, Nevanlinna Heli

KustantajaNature Research

Julkaisuvuosi2023

JournalScientific Reports

Tietokannassa oleva lehden nimiScientific Reports

Lehden akronyymiSci. Rep.

Artikkelin numero21127

Vuosikerta13

Numero1

ISSN2045-2322

eISSN2045-2322

DOIhttps://doi.org/10.1038/s41598-023-47441-w

Verkko-osoitehttps://www.nature.com/articles/s41598-023-47441-w

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/182193759


Tiivistelmä

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 × 10–5) and a low risk for heterozygous women (OR = 1.39 [1.18–1.64], P = 7.8 × 10–5). 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.


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Last updated on 2025-27-03 at 22:02