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.
N1 - Publisher Copyright:
© The Author(s).
PY - 2018
Y1 - 2018
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 - Childhood cancer survivor
KW - Genetic variations
KW - GWAS
KW - Late effects
KW - SNPs
UR - http://www.scopus.com/inward/record.url?scp=85054092877&partnerID=8YFLogxK
U2 - 10.1186/s12885-018-4834-3
DO - 10.1186/s12885-018-4834-3
M3 - Article
C2 - 30257669
AN - SCOPUS:85054092877
SN - 1471-2407
VL - 18
JO - BMC Cancer
JF - BMC Cancer
IS - 1
M1 - 930
ER -