Evidence map›Paper›PMID 34762066›Full record

ArticleJMIR research protocols2021

Identification of Genetic Predispositions Related to Ionizing Radiation in Primary Human Skin Fibroblasts From Survivors of Childhood and Second Primary Cancer as Well as Cancer-Free Controls: Protocol for the Nested Case-Control Study KiKme.

Manuela Marron, Lara Kim Brackmann, Heike Schwarz, Willempje Hummel-Bartenschlager, Sebastian Zahnreich, Danuta Galetzka, Iris Schmitt, Christian Grad, Philipp Drees, Johannes Hopf and 9 more

Open access · goldAbstract read
In one paragraph

Article in JMIR research protocols, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
4.6field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 26 citations in OpenAlex.

  1. Repair of DNA double-strand breaks after low radiation doses in childhood cancer survivors and matched cancer-free individuals.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  6. [The 41,000 long-term survivor cohort of the German Childhood Cancer Registry].Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz · 2022
    Article
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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

19 authors at 4 institutions in 1 country.

Manuela MarronLeibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.ORCID https://orcid.org/0000-0001-9658-1855
Lara Kim BrackmannLeibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.ORCID https://orcid.org/0000-0002-0484-9891
Heike SchwarzLeibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.ORCID https://orcid.org/0000-0003-2966-6861
Willempje Hummel-BartenschlagerLeibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.ORCID https://orcid.org/0000-0002-9316-7613
Sebastian ZahnreichDepartment of Radiation Oncology and Radiation Therapy, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.ORCID https://orcid.org/0000-0001-8365-3258
Danuta GaletzkaDepartment of Radiation Oncology and Radiation Therapy, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.ORCID https://orcid.org/0000-0003-1825-9136
Iris SchmittDepartment of Radiation Oncology and Radiation Therapy, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.ORCID https://orcid.org/0000-0002-6106-8047
Christian GradDepartment of Radiation Oncology and Radiation Therapy, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.ORCID https://orcid.org/0000-0001-7173-3058
Philipp DreesDepartment of Orthopedics and Traumatology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.ORCID https://orcid.org/0000-0001-6893-6524
Johannes HopfDepartment of Orthopedics and Traumatology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.ORCID https://orcid.org/0000-0001-9281-3428
Johanna MirschRadiation Biology and DNA Repair, Technical University of Darmstadt, Darmstadt, Germany.ORCID https://orcid.org/0000-0003-3596-4910
Peter Scholz-KreiselInstitute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.ORCID https://orcid.org/0000-0002-2838-6465
Peter KaatschGerman Childhood Cancer Registry, Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.ORCID https://orcid.org/0000-0002-8565-0832
Alicia PoplawskiInstitute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.ORCID https://orcid.org/0000-0003-2527-0763
Moritz HessInstitute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center Freiburg, University of Freiburg, Freiburg, Germany.ORCID https://orcid.org/0000-0003-4021-1796
Harald BinderInstitute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center Freiburg, University of Freiburg, Freiburg, Germany.ORCID https://orcid.org/0000-0002-5666-8662
Thomas HankelnInstitute of Organismic and Molecular Evolution, Molecular Genetics and Genome Analysis, Johannes Gutenberg University, Mainz, Germany.ORCID https://orcid.org/0000-0002-0677-8417
Maria BlettnerInstitute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.ORCID https://orcid.org/0000-0001-9064-9580
Heinz SchmidbergerDepartment of Radiation Oncology and Radiation Therapy, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.ORCID https://orcid.org/0000-0003-0647-8884
Johannes Gutenberg University Mainz · DELeibniz Institute for Prevention Research and Epidemiology - BIPS · DEUniversity of Freiburg · DETechnische Universität Darmstadt · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTherapy for a first primary neoplasm (FPN) in childhood with high doses of ionizing radiation is an established risk factor for second primary neoplasms (SPN). An association between exposure to low doses and childhood cancer is also suggested; however, results are inconsistent. As only subgroups of children with FPNs develop SPNs, an interaction between radiation, genetic, and other risk factors is presumed to influence cancer development.

objectiveTherefore, the population-based, nested case-control study KiKme aims to identify differences in genetic predisposition and radiation response between childhood cancer survivors with and without SPNs as well as cancer-free controls.

methodsWe conducted a population-based, nested case-control study KiKme. Besides questionnaire information, skin biopsies and saliva samples are available. By measuring individual reactions to different exposures to radiation (eg, 0.05 and 2 Gray) in normal somatic cells of the same person, our design enables us to create several exposure scenarios for the same person simultaneously and measure several different molecular markers (eg, DNA, messenger RNA, long noncoding RNA, copy number variation).

resultsSince 2013, 101 of 247 invited SPN patients, 340 of 1729 invited FPN patients, and 150 of 246 invited cancer-free controls were recruited and matched by age and sex. Childhood cancer patients were additionally matched by tumor morphology, year of diagnosis, and age at diagnosis. Participants reported on lifestyle, socioeconomical, and anthropometric factors, as well as on medical radiation history, health, and family history of diseases (n=556). Primary human fibroblasts from skin biopsies of the participants were cultivated (n=499) and cryopreserved (n=3886). DNA was extracted from fibroblasts (n=488) and saliva (n=510).

conclusionsThis molecular-epidemiological study is the first to combine observational epidemiological research with standardized experimental components in primary human skin fibroblasts to identify genetic predispositions related to ionizing radiation in childhood and SPNs. In the future, fibroblasts of the participants will be used for standardized irradiation experiments, which will inform analysis of the case-control study and vice versa. Differences between participants will be identified using several molecular markers. With its innovative combination of experimental and observational components, this new study will provide valuable data to forward research on radiation-related risk factors in childhood cancer and SPNs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/32395.

Indexed as

cell linechildhood cancerfeasibilityfibroblastirradiationneoplasmparticipationsecond cancersecond primary neoplasmstudy design

Identifiers

PMID34762066
PMCPMC8663494
OpenAlexW3197744274

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.