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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Study protocol

Genetic variation in gonadal impairment in female survivors of childhood cancer: a PanCareLIFE study protocol

Authors: Anne-Lotte L. F. van der Kooi, Eva Clemens, Linda Broer, Oliver Zolk, Julianne Byrne, Helen Campbell, Marleen van den Berg, Claire Berger, Gabriele Calaminus, Uta Dirksen, Jeanette Falck Winther, Sophie D Fosså, Desiree Grabow, Riccardo Haupt, Melanie Kaiser, Tomas Kepak, Leontien Kremer, Jarmila Kruseova, Dalit Modan-Moses, Andreas Ranft, Claudia Spix, Peter Kaatsch, Joop S. E. Laven, Eline van Dulmen-den Broeder, André G. Uitterlinden, Marry M. van den Heuvel-Eibrink, on behalf of the PanCareLIFE Consortium

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Improved risk stratification, more effective therapy and better supportive care have resulted in survival rates after childhood cancer of around 80% in developed countries. Treatment however can be harsh, and three in every four childhood cancer survivors (CCS) develop at least one late effect, such as gonadal impairment. Gonadal impairment can cause involuntary childlessness, with serious consequences for the well-being of CCS. In addition, early menopause increases the risk of comorbidities such as cardiovascular disease and osteoporosis. Inter-individual variability in susceptibility to therapy related gonadal impairment suggests a role for genetic variation.
Currently, only one candidate gene study investigated genetic determinants in relation to gonadal impairment in female CCS; it yielded one single nucleotide polymorphism (SNP) that was previously linked with the predicted age at menopause in the general population of women, now associated with gonadal impairment in CCS. Additionally, one genome wide association study (GWAS) evaluated an association with premature menopause, but no GWAS has been performed using endocrine measurements for gonadal impairment  as the primary outcome in CCS.

Methods

As part of the PanCareLIFE study, the genetic variability of chemotherapy induced gonadal impairment among CCS will be addressed. Gonadal impairment will be determined by anti-Müllerian hormone (AMH) levels or alternatively by fertility and reproductive medical history retrieved by questionnaire. Clinical and genetic data from 837 non-brain or non-bilateral gonadal irradiated long-term CCS will result in the largest clinical European cohort assembled for this late-effect study to date. A candidate gene study will examine SNPs that have already been associated with age at natural menopause and DNA maintenance in the general population. In addition, a GWAS will be performed to identify novel allelic variants. The results will be validated in an independent CCS cohort.

Discussion

This international collaboration aims to enhance knowledge of genetic variation which may be included in risk prediction models for gonadal impairment in CCS.
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Metadata
Title
Genetic variation in gonadal impairment in female survivors of childhood cancer: a PanCareLIFE study protocol
Authors
Anne-Lotte L. F. van der Kooi
Eva Clemens
Linda Broer
Oliver Zolk
Julianne Byrne
Helen Campbell
Marleen van den Berg
Claire Berger
Gabriele Calaminus
Uta Dirksen
Jeanette Falck Winther
Sophie D Fosså
Desiree Grabow
Riccardo Haupt
Melanie Kaiser
Tomas Kepak
Leontien Kremer
Jarmila Kruseova
Dalit Modan-Moses
Andreas Ranft
Claudia Spix
Peter Kaatsch
Joop S. E. Laven
Eline van Dulmen-den Broeder
André G. Uitterlinden
Marry M. van den Heuvel-Eibrink
on behalf of the PanCareLIFE Consortium
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4834-3

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