TY - JOUR
T1 - The influence of genetic variation on late toxicities in childhood cancer survivors
T2 - A review
AU - Clemens, E.
AU - van der Kooi, A. L.F.
AU - Broer, L.
AU - van Dulmen-den Broeder, E.
AU - Visscher, H.
AU - Kremer, L.
AU - Tissing, W.
AU - Loonen, J.
AU - Ronckers, C. M.
AU - Pluijm, S. M.F.
AU - Neggers, S. J.C.M.M.
AU - Zolk, O.
AU - Langer, T.
AU - Zehnhoff-Dinnesen, A. am
AU - Wilson, C. L.
AU - Hudson, M. M.
AU - Carleton, B.
AU - Laven, J. S.E.
AU - Uitterlinden, A. G.
AU - van den Heuvel-Eibrink, M. M.
N1 - Funding Information:
We would like to thank W.M Bramer for supporting the literature search. This work was supported by the PanCareLIFE project that has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no 602030 (EC and ALFvdK). CMR is supported by the Dutch Cancer Society.
Funding Information:
We would like to thank W.M Bramer for supporting the literature search. This work was supported by the PanCareLIFE project that has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 602030 (EC and ALFvdK). CMR is supported by the Dutch Cancer Society .
Publisher Copyright:
© 2018 The Authors
PY - 2018/6/1
Y1 - 2018/6/1
N2 - INTRODUCTION: The variability in late toxicities among childhood cancer survivors (CCS) is only partially explained by treatment and baseline patient characteristics. Inter-individual variability in the association between treatment exposure and risk of late toxicity suggests that genetic variation possibly modifies this association. We reviewed the available literature on genetic susceptibility of late toxicity after childhood cancer treatment related to components of metabolic syndrome, bone mineral density, gonadal impairment and hearing impairment.METHODS: A systematic literature search was performed, using Embase, Cochrane Library, Google Scholar, MEDLINE, and Web of Science databases. Eligible publications included all English language reports of candidate gene studies and genome wide association studies (GWAS) that aimed to identify genetic risk factors associated with the four late toxicities, defined as toxicity present after end of treatment.RESULTS: Twenty-seven articles were identified, including 26 candidate gene studies: metabolic syndrome (n = 6); BMD (n = 6); gonadal impairment (n = 2); hearing impairment (n = 12) and one GWAS (metabolic syndrome). Eighty percent of the genetic studies on late toxicity after childhood cancer had relatively small sample sizes (n < 200), leading to insufficient power, and lacked adjustment for multiple comparisons. Only four (4/26 = 15%) candidate gene studies had their findings validated in independent replication cohorts as part of their own report.CONCLUSION: Genetic susceptibility associations are not consistent or not replicated and therefore, currently no evidence-based recommendations can be made for hearing impairment, gonadal impairment, bone mineral density impairment and metabolic syndrome in CCS. To advance knowledge related to genetic variation influencing late toxicities among CCS, future studies need adequate power, independent cohorts for replication, harmonization of disease outcomes and sample collections, and (international) collaboration.
AB - INTRODUCTION: The variability in late toxicities among childhood cancer survivors (CCS) is only partially explained by treatment and baseline patient characteristics. Inter-individual variability in the association between treatment exposure and risk of late toxicity suggests that genetic variation possibly modifies this association. We reviewed the available literature on genetic susceptibility of late toxicity after childhood cancer treatment related to components of metabolic syndrome, bone mineral density, gonadal impairment and hearing impairment.METHODS: A systematic literature search was performed, using Embase, Cochrane Library, Google Scholar, MEDLINE, and Web of Science databases. Eligible publications included all English language reports of candidate gene studies and genome wide association studies (GWAS) that aimed to identify genetic risk factors associated with the four late toxicities, defined as toxicity present after end of treatment.RESULTS: Twenty-seven articles were identified, including 26 candidate gene studies: metabolic syndrome (n = 6); BMD (n = 6); gonadal impairment (n = 2); hearing impairment (n = 12) and one GWAS (metabolic syndrome). Eighty percent of the genetic studies on late toxicity after childhood cancer had relatively small sample sizes (n < 200), leading to insufficient power, and lacked adjustment for multiple comparisons. Only four (4/26 = 15%) candidate gene studies had their findings validated in independent replication cohorts as part of their own report.CONCLUSION: Genetic susceptibility associations are not consistent or not replicated and therefore, currently no evidence-based recommendations can be made for hearing impairment, gonadal impairment, bone mineral density impairment and metabolic syndrome in CCS. To advance knowledge related to genetic variation influencing late toxicities among CCS, future studies need adequate power, independent cohorts for replication, harmonization of disease outcomes and sample collections, and (international) collaboration.
KW - Bone Density/genetics
KW - Cancer Survivors/statistics & numerical data
KW - Drug-Related Side Effects and Adverse Reactions/epidemiology
KW - Genetic Predisposition to Disease
KW - Genetic Variation/physiology
KW - Genome-Wide Association Study
KW - Humans
KW - Late Onset Disorders/epidemiology
KW - Metabolic Syndrome/epidemiology
KW - Neoplasms/epidemiology
KW - Radiation Injuries/epidemiology
KW - Time Factors
UR - http://www.scopus.com/inward/record.url?scp=85045686172&partnerID=8YFLogxK
U2 - 10.1016/j.critrevonc.2018.04.001
DO - 10.1016/j.critrevonc.2018.04.001
M3 - Review article
C2 - 29759558
AN - SCOPUS:85045686172
SN - 1040-8428
VL - 126
SP - 154
EP - 167
JO - Critical Reviews in Oncology/Hematology
JF - Critical Reviews in Oncology/Hematology
ER -