Format

Send to

Choose Destination
BMC Cancer. 2018 Sep 26;18(1):930. doi: 10.1186/s12885-018-4834-3.

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

Author information

1
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands. a.vanderkooi@erasmusmc.nl.
2
Department of Pediatric Hematology and Oncology, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands. a.vanderkooi@erasmusmc.nl.
3
Princess Máxima Center for Pediatric Oncology, Lundlaan 6, 3584, EA, Utrecht, The Netherlands. a.vanderkooi@erasmusmc.nl.
4
Department of Pediatric Hematology and Oncology, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands.
5
Princess Máxima Center for Pediatric Oncology, Lundlaan 6, 3584, EA, Utrecht, The Netherlands.
6
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
7
Institute of Pharmacology of Natural Products and Clinical Pharmacology, University Hospital Ulm, Ulm, Germany.
8
Boyne Research Institute, Drogheda, Ireland.
9
Department of Pediatric Hematology and Oncology, VU Medical Center, Amsterdam, The Netherlands.
10
Department of Paediatric Oncology, University Hospital, St-Etienne, France.
11
Epidemiology of Childhood and Adolescent Cancers, CRESS, INSERM, UMR 1153, Paris Descartes University, Villejuif, France.
12
Department of Paediatric Haematology and Oncology, University Children's Hospital Bonn, University of Bonn Medical School, Bonn, Germany.
13
Pediatrics III, West German Cancer Centre, University Hospital Essen, Essen, Germany.
14
German Cancer Research Centre, DKTK, sites Bonn and Essen, Germany.
15
Danish Cancer Society Research Center, Copenhagen, Denmark.
16
Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
17
Department of Oncology, Oslo University Hospital, Oslo, Norway.
18
German Childhood Cancer Registry, Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center, Mainz, Germany.
19
Epidemiology and Biostatistics Unit, Istituto Giannina Gaslini, Genoa, Italy.
20
Czech Republic & International Clinical Research Center (FNUSA-ICRC), University Hospital Brno, Brno, Czech Republic.
21
Department of Pediatrics, Academic Medical Center, Emma Children's Hospital, Amsterdam, The Netherlands.
22
Motol University Hospital, Prague, Czech Republic.
23
Chaim Sheba Medical Center, The Edmond and Lily Safra Children's Hospital, Tel Hashomer, Israel.
24
Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
25
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands.

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.

KEYWORDS:

Childhood cancer survivor; GWAS; Genetic variations; Late effects; SNPs

PMID:
30257669
PMCID:
PMC6158859
DOI:
10.1186/s12885-018-4834-3
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central Icon for Norwegian BIBSYS system
Loading ...
Support Center