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

Overview

Journal JMIR Res Protoc

Publisher JMIR Publications

Specialty General Medicine

Date 2021 Nov 11

PMID 34762066

Citations 6

Authors

Manuela Marron

Lara Kim Brackmann

Heike Schwarz

Willempje Hummel-Bartenschlager

Sebastian Zahnreich

Danuta Galetzka

Iris Schmitt

Christian Grad

Philipp Drees

Johannes Hopf

Johanna Mirsch

Peter Scholz-Kreisel

Peter Kaatsch

Alicia Poplawski

Moritz Hess

Harald Binder

Thomas Hankeln

Maria Blettner

Heinz Schmidberger

Affiliations

Soon will be listed here.

Abstract

Background: Therapy 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.

Objective: Therefore, 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.

Methods: We 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).

Results: Since 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).

Conclusions: This 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.

Citing Articles

Identification of lncRNAs involved in response to ionizing radiation in fibroblasts of long-term survivors of childhood cancer and cancer-free controls.

Grandt C, Brackmann L, Poplawski A, Schwarz H, Marini F, Hankeln T Front Oncol. 2023; 13:1158176.

PMID: 37182169 PMC: 10174438. DOI: 10.3389/fonc.2023.1158176.

Self-administered questionnaire assessing childhood cancer treatments and associated risks for adverse health outcomes - The KiKme study.

Brackmann L, Foraita R, Schwarz H, Poplawski A, Hankeln T, Galetzka D Front Oncol. 2023; 13:1150629.

PMID: 37124517 PMC: 10147395. DOI: 10.3389/fonc.2023.1150629.

Gene expression variability in long-term survivors of childhood cancer and cancer-free controls in response to ionizing irradiation.

Grandt C, Brackmann L, Foraita R, Schwarz H, Hummel-Bartenschlager W, Hankeln T Mol Med. 2023; 29(1):41.

PMID: 36997855 PMC: 10061869. DOI: 10.1186/s10020-023-00629-2.

Late health effects and changes in lifestyle factors after cancer in childhood with and without subsequent second primary cancers - the KiKme case-control study.

Brackmann L, Foraita R, Schwarz H, Galetzka D, Zahnreich S, Hankeln T Front Oncol. 2022; 12:1037276.

PMID: 36324589 PMC: 9618813. DOI: 10.3389/fonc.2022.1037276.

Radiation-response in primary fibroblasts of long-term survivors of childhood cancer with and without second primary neoplasms: the KiKme study.

Grandt C, Brackmann L, Poplawski A, Schwarz H, Hummel-Bartenschlager W, Hankeln T Mol Med. 2022; 28(1):105.

PMID: 36068491 PMC: 9450413. DOI: 10.1186/s10020-022-00520-6.

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