What you carry at this position in your DNA and what research says about it.
Chemotherapy Hearing Loss: 6/10 evidence, 9 publications.
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Sample genotype (not yours): C/C
Typical Risk of Chemotherapy-Induced Hearing Loss
A typical response to cisplatin chemotherapy is expected, with no elevated risk of hearing damage. Baseline risk for bone cancer also remains typical.
What this genotype means: Typical risk of cisplatin-induced hearing loss; Typical baseline risk of osteosarcoma.
Sample genotype (not yours): C/T
Increased Risk of Chemotherapy-Induced Hearing Loss
One copy of the T allele is linked to a higher risk of permanent hearing damage if treated with cisplatin chemotherapy. Susceptibility to bone cancer is also slightly increased.
What this genotype means: Elevated risk of cisplatin-induced hearing loss; Increased susceptibility to osteosarcoma.
Sample genotype (not yours): T/T
Higher Risk of Chemotherapy-Induced Hearing Loss
Two copies of the T allele are associated with a significantly elevated risk of permanent hearing damage from cisplatin chemotherapy. Susceptibility to bone cancer is also increased.
What this genotype means: Significantly elevated risk of cisplatin-induced hearing loss; Increased susceptibility to osteosarcoma.
Gene function and biological role
Gene Function: ARVCF encodes a catenin family member involved in cell adhesion and signaling, while the overlapping COMT gene metabolizes catecholamines and catechol estrogens [1]. These genes are located in the 22q11.2 region, which is highly linked to neurodevelopmental and pain-related traits [2]. Variations in this region can influence how the body processes certain chemotherapeutic drugs like cisplatin [3].
Variant Impact: Located within an intron of the ARVCF gene, rs9332377 is a genetic change that overlaps with the 3 prime region of the COMT gene. This genetic change is thought to modulate the expression of these neighboring genes, affecting drug metabolism and cellular response to stress. It has been studied primarily in the context of cisplatin chemotherapy, where it is associated with a significantly higher risk of permanent hearing loss in pediatric patients [1]. Additionally, genome-wide studies have linked this variant to bone cancer susceptibility [4].
Key Insight: This genetic variant is located in a unique overlapping region between two genes, meaning it can simultaneously influence pain sensitivity, bone health, and chemotherapy side effects.
Location: ARVCF. Chromosome 22 · 22q11.21 · 20.0 Mb
Estimated prevalence by population
Global 64.6%; European 70.8%; African 42.9%; East Asian 99.4%; South Asian 70.7%; Americas 74.2%; Ashkenazi 59.8%; Finnish 76.3%; Middle Eastern 61.7%; Amish 82.2%.
Estimated CC genotype frequency.
Global 30.4%; European 26.7%; African 45.2%; East Asian 0.6%; South Asian 26.7%; Americas 23.9%; Ashkenazi 35.1%; Finnish 22.1%; Middle Eastern 33.7%; Amish 16.9%.
Estimated CT genotype frequency.
Global 5.0%; European 2.5%; African 11.9%; East Asian < 0.1%; South Asian 2.5%; Americas 1.9%; Ashkenazi 5.1%; Finnish 1.6%; Middle Eastern 4.6%; Amish 0.9%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Pharmacogenomics
Chemotherapy Response
Cisplatin Hearing Loss. Evidence: 6/10. Source: PMID 19898482. Typical Risk.
Cancer & Oncology
Blood Cancers
Osteosarcoma. Evidence: 4/10. Source: PMID 29210060. Typical Risk.
Cancer Prognosis & Treatment Outcome
Overall Survival. Evidence: 4/10. Source: PMID 29210060. Unresolved.
Organ Systems
Bone, Joint & Connective Tissue Health
Scoliosis. Evidence: 3/10. Source: PMID 30019117. Unresolved.
Showing effects for C/T genotype
Cisplatin Hearing Loss. Evidence: 6/10. Source: PMID 19898482. Increased Risk.
Osteosarcoma. Evidence: 4/10. Source: PMID 29210060. ~1.78x Risk.
Showing effects for T/T genotype
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Two copies of the C allele represent the most common genetic profile globally. Clinical studies have shown that pediatric patients with this specific profile do not have an increased susceptibility to cisplatin-induced ototoxicity, a form of permanent hearing loss caused by chemotherapy [1]. Furthermore, genome-wide association studies indicate that this genetic setup is associated with a typical baseline risk for osteosarcoma, a primary bone cancer [2]. Because this profile lacks the risk-associated T allele, it is considered the protective baseline profile for these conditions. It is also associated with typical pain sensitivity and spinal health.
Typical risk of cisplatin-induced hearing loss; Typical baseline risk of osteosarcoma.
Sample genotype: CT (Heterozygous)
One copy of the risk-associated T allele is present in this genetic profile. Research in pediatric oncology has demonstrated that this specific genetic setup is linked to a significantly higher risk of developing cisplatin-induced hearing loss during cancer treatment [1]. The T allele is believed to alter the expression of genes involved in drug metabolism and cellular defense, making the inner ear more vulnerable to chemotherapy toxicity. Additionally, genome-wide studies have linked this profile to an increased risk of osteosarcoma [2]. Understanding this genetic predisposition can help clinicians optimize treatment monitoring and explore protective strategies.
Elevated risk of cisplatin-induced hearing loss; Increased susceptibility to osteosarcoma.
Sample genotype: TT (Homozygous)
Two copies of the T allele represent the highest genetic risk profile for cisplatin-induced ototoxicity. Clinical trials have consistently identified that patients with this specific profile are highly susceptible to severe, irreversible hearing loss when undergoing cisplatin-based chemotherapy [1]. The genetic variation in this region is thought to reduce the body's ability to clear or detoxify platinum-based drugs, leading to cellular damage in the inner ear. Furthermore, genome-wide association studies have shown that this profile is associated with a significantly increased risk of developing osteosarcoma [2]. These findings highlight the importance of genetic screening in personalizing cancer therapies.
Significantly elevated risk of cisplatin-induced hearing loss; Increased susceptibility to osteosarcoma.
Variants with shared genetic architecture
rs12201199 · TPMT Gene · Chr 6 · Cisplatin Hearing Loss
rs4646316 · COMT Gene · Chr 22 · Cisplatin Hearing Risk
rs267606618 · Chr M · Antibiotic Hearing Loss Risk
Genetic markers of cisplatin-induced hearing loss in children.
Content updated August 2026.
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