# Genetic Associations with Hearing Loss from Cancer Treatment

> **NIH VA I21** · PORTLAND VA MEDICAL CENTER · 2020 · —

## Abstract

Approximately 1 in 3 Americans will be diagnosed with cancer in their lifetime (IOM, 2006). Within VA last
year alone, an estimated 10,421 patients received platinum-based chemotherapy with cisplatin [2,443],
carboplatin [5,621], or oxaliplatin [2357] (VA Cancer Registry, 2018). These are common treatments for myriad
cancers (Rybak, 2007; Miaskowski et al., 2018; Sogaard et al., 2013) and are known to cause lasting damage
to the ear [ototoxic]. The reported incidence of sensorineural hearing loss (SNHL) and tinnitus arising from these
treatments varies considerably. Pre-treatment knowledge of the genetic indicators of ototoxicity could improve
the accuracy of ototoxicity risk estimates, and prompt intervention to potentially prevent SNHL, tinnitus, and the
related psychosocial impacts for these patients. This is important because these auditory problems are grossly
underdiagnosed and undertreated (Chou et al., 2011; Cunningham & Tucci, 2017). However, it remains unclear
why some patients retain their pre-treatment auditory function despite high cumulative drug dosing (Rybak ,2007;
Obermair et al., 1998), thus suggesting genetic susceptibility (Tserga et al., 2019).
 The objective of this proposed research is to test for genetic associations of 3 candidate genes: ACYP2, (Xu
et al., 2015), TPMT (Ross et al., 2009), and TRPV1 (Jian et al., 2019) with well-characterized ototoxicity. We will
incorporate locally developed, behavioral and non-behavioral auditory tests and risk factor models to provide
proof of principle and sample size calculations for replication and a genome wide association study (GWAS) in
a multi-site context. The specific aims are to gather preliminary evidence of: (1) Associations of candidate genes
with SNHL and tinnitus in patients found to be vulnerable or resilient to ototoxicity from cancer treatment; and
(2) Associations of candidate genes with outer hair cell and synaptic/neural integrity following cancer treatment.
 We will obtain blood and genetic samples from approximately 150 participants in Dr. Konrad-Martin’s new
and completed projects on ototoxicity. By recruiting from these samples, we leverage a rich data set that will
provide the comprehensive, audiometric and physiological, auditory phenotyping necessary to conduct this
study. In Year 1, we will focus on recruiting and obtaining blood draws from participants, obtaining data on their
cancer treatment using the electronic medical record (EMR) at the VA and at Oregon Health & Science
University, extracting genomic DNA, and developing tags for the single nucleotide polymorphisms (SNPs)
associated with each candidate gene. These data will be used in Aim 1 to verify if a set of candidate genes
potentiates platinum-drug-induced SNHL or tinnitus in clinical models of cisplatin-, carboplatin- and oxaliplatin-
ototoxicity. Pre-clinical models demonstrate that carboplatin and oxaliplatin induce cochlear synaptic/neural
dysfunction without the same degree of outer hair cell ...

## Key facts

- **NIH application ID:** 10016914
- **Project number:** 1I21RX003483-01
- **Recipient organization:** PORTLAND VA MEDICAL CENTER
- **Principal Investigator:** DAWN L KONRAD-MARTIN
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10016914

## Citation

> US National Institutes of Health, RePORTER application 10016914, Genetic Associations with Hearing Loss from Cancer Treatment (1I21RX003483-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10016914. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*