Evidence map›Paper›PMID 40009290›Full record

ArticleBreast cancer research and treatment2025

Population-based study of recurrent DNA damage response gene variants in breast cancer cases.

Anna Tervasmäki, Timo A Kumpula, Mervi Grip, Susanna Koivuluoma, Meeri Seuranen, Robert Winqvist, Tuomo Mantere, Katri Pylkäs

Abstract read
In one paragraph

Article in Breast cancer research and treatment, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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0cells of the map it votes in
2citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Anna TervasmäkiLaboratory of Cancer Genetics and Tumor Biology, Translational Medicine Research Unit, University of Oulu, Aapistie 5A, 90220, Oulu, Finland.
Timo A KumpulaLaboratory of Cancer Genetics and Tumor Biology, Translational Medicine Research Unit, University of Oulu, Aapistie 5A, 90220, Oulu, Finland.
Mervi GripDepartment of Surgery, Oulu University Hospital and University of Oulu, Oulu, Finland.
Susanna KoivuluomaLaboratory of Cancer Genetics and Tumor Biology, Translational Medicine Research Unit, University of Oulu, Aapistie 5A, 90220, Oulu, Finland.
Meeri SeuranenLaboratory of Cancer Genetics and Tumor Biology, Translational Medicine Research Unit, University of Oulu, Aapistie 5A, 90220, Oulu, Finland.
Robert WinqvistLaboratory of Cancer Genetics and Tumor Biology, Translational Medicine Research Unit, University of Oulu, Aapistie 5A, 90220, Oulu, Finland.
Tuomo MantereLaboratory of Cancer Genetics and Tumor Biology, Translational Medicine Research Unit, University of Oulu, Aapistie 5A, 90220, Oulu, Finland.
Katri PylkäsLaboratory of Cancer Genetics and Tumor Biology, Translational Medicine Research Unit, University of Oulu, Aapistie 5A, 90220, Oulu, Finland. katri.pylkas@oulu.fi.

Funding

the Academy of Finland 361305
6 · The paper itself

Abstract

purposeSeveral variants in DNA damage response (DDR) genes increase the probability to develop breast cancer and show enrichment in Northern Finland. Here, the population prevalence and risk estimations were refined for sixteen recurrent pathogenic/likely pathogenic DDR gene variants.

methodsVariant genotyping was performed in 2343 unselected Northern Finnish breast cancer cases and 4607 cancer-free controls, and tumor features and family history of cancer for the carriers were examined.

resultsBased on their prevalence and carrier family history, the studied BRCA1 and BRCA2 variants, PALB2 c.1592delT, and ATM c.7570G > C were confirmed as high-risk alleles, whereas CHEK2 c.1100delC, MCPH1 c.909_921del, and RAD50 c.687delT were moderate-risk alleles. FANCM c.5101C > T and c.5791C > T did not associate with overall breast cancer risk. Double carriers were significantly more common in cases (0.5%, 11/2343) than controls (0.07%, 3/4601, OR 7.2). The BRCA1/2 and PALB2 c.1592delT carrier tumors all had high proliferation rates, PALB2 c.1592delT associating also with grade 3 tumors (p = 0.002). Progesterone receptor (p < 0.05) and estrogen receptor positive tumors were enriched in ATM c.7570G > C and CHEK2 c.1100delC carriers, whereas MCPH1 c.904_916del carriers had a significantly high percentage of multifocal tumors (38%, p = 0.001). Moreover, one FANCM c.5101C > T homozygote case suffered severe side effects from chemotherapy.

conclusionThe studied DDR gene variants were present in 9% of the unselected cases. As the presence of germline pathogenic variants can provide additional value for surgical decision-making and affect the choice of oncological treatments, the results promote the benefits of genetic testing as a part of breast cancer diagnostics.

Indexed as

Breast NeoplasmsDNA DamageAdultAgedAllelesAtaxia Telangiectasia Mutated ProteinsBRCA1 ProteinBRCA2 ProteinCase-Control StudiesCheckpoint Kinase 2Fanconi Anemia Complementation Group N ProteinFemaleFinlandGenetic Predisposition to DiseaseGenetic VariationGenotypeAtaxia Telangiectasia Mutated ProteinsBRCA1 ProteinBRCA1 protein, humanBRCA2 ProteinCheckpoint Kinase 2CHEK2 protein, humanFanconi Anemia Complementation Group N ProteinPALB2 protein, humanBreast cancerDNA damage response gene variantsDouble heterozygoteGenetics of cancer risk

Identifiers

PMID40009290
PMCPMC11953123

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.