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GWAS Study

TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study.

Meijer AJM, Diepstraten FA, Langer T et al.

34262104 PubMed ID
GWAS Study Type
770 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

MA
Meijer AJM
DF
Diepstraten FA
LT
Langer T
BL
Broer L
DI
Domingo IK
CE
Clemens E
UA
Uitterlinden AG
DV
de Vries ACH
VG
van Grotel M
VW
Vermeij WP
OR
Ozinga RA
BH
Binder H
BJ
Byrne J
VD
van Dulmen-den Broeder E
GM
Garrè ML
GD
Grabow D
KP
Kaatsch P
KM
Kaiser M
KL
Kenborg L
WJ
Winther JF
RC
Rechnitzer C
HH
Hasle H
KT
Kepak T
KK
Kepakova K
TW
Tissing WJE
VD
van der Kooi ALF
KL
Kremer LCM
KJ
Kruseova J
PS
Pluijm SMF
KC
Kuehni CE
VD
van der Pal HJH
PR
Parfitt R
SC
Spix C
TA
Tillmanns A
DD
Deuster D
MP
Matulat P
CG
Calaminus G
HA
Hoetink AE
ES
Elsner S
GJ
Gebauer J
HR
Haupt R
LH
Lackner H
BC
Blattmann C
NS
Neggers SJCMM
RS
Rassekh SR
WG
Wright GEB
BB
Brooks B
NA
Nagtegaal AP
DB
Drögemöller BI
RC
Ross CJD
BA
Bhavsar AP
AZ
Am Zehnhoff-Dinnesen AG
CB
Carleton BC
ZO
Zolk O
VD
van den Heuvel-Eibrink MM
Chapter II

Abstract

Summary of the research findings

In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P = 5.3 × 10-10, OR 3.11, 95% CI 2.2-4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity.

168 European ancestry, African American or Afro-Caribbean, Hispanic or Latin American child cases, 222 European, African American or Afro-Caribbean, Hispanic or Latin American ancestry child controls

Chapter III

Study Statistics

Key metrics and study information

770
Total Participants
GWAS
Study Type
Yes
Replicated
209 child cases, 171 child controls
Replication Participants
African American or Afro-Caribbean, European, Hispanic or Latin American
Ancestry
Austria, Czech Republic, Denmark, Germany, Italy, Netherlands, Switzerland
Recruitment Country
Chapter IV

Analysis

Comprehensive review of health and genetic findings

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