Promoter region variation in NFE2L2 influences susceptibility to ototoxicity in patients exposed to high cumulative doses of cisplatin


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Ototoxicity is a disabling reaction to cisplatin chemotherapy. Much of the inter-individual variability in the development of hearing impairment among cisplatin-receiving patients has not


been fully accounted for. In particular, little is known about the pharmacogenomics of cisplatin-induced ototoxicity. This study sought to investigate the role of variation in five candidate


genes in a cohort of South African cancer patients. Five variants within the candidate genes were genotyped in 214 patients, of which SLC22A2 rs316019 and NFE2L2 rs6721961 associated with


reduced rates of ototoxicity. In the patients who were exposed to cumulative cisplatin doses ⩾200 mg m−2 (n=113), the variant rs6721961 associated with ototoxicity according to three


different grading scales of hearing loss (ASHA, P=0.005; Chang, P=0.028; CTCAE, P=0.004). The NFE2L2 promotor variant rs6721961 may therefore be protective against hearing loss in


cisplatin-receiving cancer patients.


We thank the NRF and MRC SA for funding this research, and Sr Gameda Benefeld for recruitment of the patient cohort.


Division of Human Genetics, MRC Human Genetics Research Unit, Institute for Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South


Africa


Division of Communication Sciences and Disorders, Groote Schuur Hospital, Cape Town, South Africa


Department of Radiation Oncology, Groote Schuur Hospital, Cape Town, South Africa


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