KEY TAKEAWAYS
- The study aimed to assess the impact of genetic variants on enhancing predictions of CIHL in patients with HNSCC.
- Researchers noted the rs2289669 SNP’s key role in predicting CIHL, emphasizing the value of combining genetic and clinical data.
High-dose cisplatin combined with radiotherapy is a standard treatment for head and neck squamous cell carcinoma (HNSCC). This regimen is associated with irreversible sensorineural hearing loss, and the variability in patient responses suggests a genetic influence.
Charlotte W Duinkerken and the team aimed to enhance the predictive ability of the clinical prediction model for cisplatin-induced hearing loss (CIHL) in patients with HNSCC, as outlined in Theunissen et al., by incorporating significant genetic variants.
They performed an inclusive analysis at the Netherlands Cancer Institute, involving 74 patients treated between 1997 and 2011. They identified and incorporated 31 SNPs previously linked to CIHL or other cisplatin-related toxicities into their model.
The primary outcome measured was the change in hearing levels in decibels at posttreatment 1, 2, and 4 kHz frequencies per additional minor allele of these SNPs, evaluated using linear mixed-effects regression models. The model’s predictive accuracy was assessed through the area under the curve (AUC) using 10-fold cross-validation.
About the rs2289669 SNP in the SLC47A1/MATE1 gene, a significant 2.67 dB increase in hearing loss per allele was observed (95% CI 0.49-4.86, P = 0.017). Incorporating rs2289669 into the model improved the AUC from 0.78 to 0.83, representing a borderline significant enhancement (P = 0.073).
The study concluded that the rs2289669 SNP plays a critical role in predicting CIHL and highlighted the potential benefits of integrating genetic and clinical data to improve predictive models and personalize treatment strategies.
This study was funded by the Princess Margaret Cancer Centre Head & Neck Translational Program, with philanthropic funds from the Wharton Family, Joe’s Team, and Gordon Tozer.
Source: https://pubmed.ncbi.nlm.nih.gov/39159054/
Duinkerken CW, Chiodo S, Hueniken K, et al. (2024). “The role of genetic variants in the prediction of hearing loss due to cisplatin chemoradiotherapy. Cancer Med.” 2024 Aug;13(16):e7465. doi: 10.1002/cam4.7465. PMID: 39159054.
