TY - JOUR
T1 - Influence of Genetic Variants in TPMT and COMT Associated with Cisplatin Induced Hearing Loss in Patients with Cancer
T2 - Two New Cohorts and a Meta-Analysis Reveal Significant Heterogeneity between Cohorts
AU - Hagleitner, Melanie M.
AU - Coenen, Marieke J. H.
AU - Patino-Garcia, Ana
AU - de Bont, Eveline S. J. M.
AU - Gonzalez-Neira, Anna
AU - Vos, Hanneke I.
AU - van Leeuwen, Frank N.
AU - Gelderblom, Hans
AU - Hoogerbrugge, Peter M.
AU - Guchelaar, Henk-Jan
AU - te Loo, Maroeska W. M.
PY - 2014/12/31
Y1 - 2014/12/31
N2 - Treatment with cisplatin-containing chemotherapy regimens causes hearing loss in 40-60% of cancer patients. It has been suggested that genetic variants in the genes encoding thiopurine S-methyltransferase (TPMT) and catechol O-methyltransferase (COMT) can predict the development of cisplatin-induced ototoxicity and may explain interindividual variability in sensitivity to cisplatininduced hearing loss. Two recently published studies however, sought to validate these findings and showed inconsistent results. The aim of this study was to evaluate the role of polymorphisms in the TPMT and COMT genes in cisplatin-induced ototoxicity. Therefore we investigated two independent cohorts of 110 Dutch and 38 Spanish patients with osteosarcoma and performed a meta-analysis including all previously published studies resulting in a total population of 664 patients with cancer. With this largest meta-analysis performed to date, we show that the influence of TPMT and COMT on the development of cisplatin-induced hearing loss may be less important than previously suggested.
AB - Treatment with cisplatin-containing chemotherapy regimens causes hearing loss in 40-60% of cancer patients. It has been suggested that genetic variants in the genes encoding thiopurine S-methyltransferase (TPMT) and catechol O-methyltransferase (COMT) can predict the development of cisplatin-induced ototoxicity and may explain interindividual variability in sensitivity to cisplatininduced hearing loss. Two recently published studies however, sought to validate these findings and showed inconsistent results. The aim of this study was to evaluate the role of polymorphisms in the TPMT and COMT genes in cisplatin-induced ototoxicity. Therefore we investigated two independent cohorts of 110 Dutch and 38 Spanish patients with osteosarcoma and performed a meta-analysis including all previously published studies resulting in a total population of 664 patients with cancer. With this largest meta-analysis performed to date, we show that the influence of TPMT and COMT on the development of cisplatin-induced hearing loss may be less important than previously suggested.
KW - INDUCED OTOTOXICITY
KW - RISK-FACTORS
KW - INNER-EAR
KW - CHILDREN
KW - CHEMOTHERAPY
U2 - 10.1371/journal.pone.0115869
DO - 10.1371/journal.pone.0115869
M3 - Article
C2 - 25551397
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 12
M1 - e115869
ER -