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

PanCareLIFE consortium

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)930
JournalBMC Cancer
Volume18
Issue number1
DOIs
Publication statusPublished - Sep 26 2018

Fingerprint

Survivors
Neoplasms
Genome-Wide Association Study
Menopause
Single Nucleotide Polymorphism
Premature Menopause
Reproductive History
Developed Countries
Population
Genes
Osteoporosis
Fertility
Comorbidity
Cardiovascular Diseases
Therapeutics
Survival Rate
Maintenance
Hormones
Drug Therapy
DNA

Keywords

  • Adult Survivors of Child Adverse Events
  • Anti-Mullerian Hormone/analysis
  • Cancer Survivors
  • Female
  • Genome-Wide Association Study
  • Humans
  • Menopause, Premature/genetics
  • Polymorphism, Single Nucleotide
  • Surveys and Questionnaires

Cite this

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

In: BMC Cancer, Vol. 18, No. 1, 26.09.2018, p. 930.

Research output: Contribution to journalArticle

@article{ba8eb9ecd0d84f099fc6fc0dbb3600fe,
title = "Genetic variation in gonadal impairment in female survivors of childhood cancer: a PanCareLIFE study protocol",
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-M{\"u}llerian 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 = "Adult Survivors of Child Adverse Events, Anti-Mullerian Hormone/analysis, Cancer Survivors, Female, Genome-Wide Association Study, Humans, Menopause, Premature/genetics, Polymorphism, Single Nucleotide, Surveys and Questionnaires",
author = "{PanCareLIFE consortium} and {van der Kooi}, {Anne-Lotte L F} and Eva Clemens and Linda Broer and Oliver Zolk and Julianne Byrne and Helen Campbell and {van den Berg}, Marleen and Claire Berger and Gabriele Calaminus and Uta Dirksen and Winther, {Jeanette Falck} and Foss{\aa}, {Sophie D} and Desiree Grabow and Riccardo Haupt and Melanie Kaiser and Tomas Kepak and Leontien Kremer and Jarmila Kruseova and Dalit Modan-Moses and Andreas Ranft and Claudia Spix and Peter Kaatsch and Laven, {Joop S E} and {van Dulmen-den Broeder}, Eline and Uitterlinden, {Andr{\'e} G} and {van den Heuvel-Eibrink}, {Marry M}",
year = "2018",
month = "9",
day = "26",
doi = "10.1186/s12885-018-4834-3",
language = "English",
volume = "18",
pages = "930",
journal = "BMC Cancer",
issn = "1471-2407",
publisher = "BioMed Central Ltd.",
number = "1",

}

TY - JOUR

T1 - Genetic variation in gonadal impairment in female survivors of childhood cancer

T2 - a PanCareLIFE study protocol

AU - PanCareLIFE consortium

AU - van der Kooi, Anne-Lotte L F

AU - Clemens, Eva

AU - Broer, Linda

AU - Zolk, Oliver

AU - Byrne, Julianne

AU - Campbell, Helen

AU - van den Berg, Marleen

AU - Berger, Claire

AU - Calaminus, Gabriele

AU - Dirksen, Uta

AU - Winther, Jeanette Falck

AU - Fosså, Sophie D

AU - Grabow, Desiree

AU - Haupt, Riccardo

AU - Kaiser, Melanie

AU - Kepak, Tomas

AU - Kremer, Leontien

AU - Kruseova, Jarmila

AU - Modan-Moses, Dalit

AU - Ranft, Andreas

AU - Spix, Claudia

AU - Kaatsch, Peter

AU - Laven, Joop S E

AU - van Dulmen-den Broeder, Eline

AU - Uitterlinden, André G

AU - van den Heuvel-Eibrink, Marry M

PY - 2018/9/26

Y1 - 2018/9/26

N2 - 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.

AB - 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.

KW - Adult Survivors of Child Adverse Events

KW - Anti-Mullerian Hormone/analysis

KW - Cancer Survivors

KW - Female

KW - Genome-Wide Association Study

KW - Humans

KW - Menopause, Premature/genetics

KW - Polymorphism, Single Nucleotide

KW - Surveys and Questionnaires

U2 - 10.1186/s12885-018-4834-3

DO - 10.1186/s12885-018-4834-3

M3 - Article

C2 - 30257669

VL - 18

SP - 930

JO - BMC Cancer

JF - BMC Cancer

SN - 1471-2407

IS - 1

ER -