![]() Which consisted of primarily four cycles of EP (etoposide and cisplatin) or three cycles of BEP (bleomycin, etoposide, and cisplatin). To ascertain both genetic risk factors and modifiable comorbidities for cisplatin‐induced toxicities, we constructed the Platinum Study, a well‐phenotyped cohort of testicular cancer survivors (TCS) treated with homogenous cisplatin‐based chemotherapy, However, clinical implementation of assessing genetic biomarkers and counseling patients with nongenetic comorbidities with regard to potential toxicities has been limited. There are attempts to identify individuals a priori who are more likely to develop these sequelae through studies of genetic risk factors and nongenetic comorbidities. Unfortunately, there are no approved preventive measures and no FDA‐approved drug therapies for these toxicities however, patients would benefit from individualized risk assessments, allowing for detailed education and counseling, and the development of a personalized treatment and monitoring plan. ![]() More than 5.8 million patients (pediatric and adults) globally are diagnosed each year with cancers (e.g., testicular, ovarian, bladder, lung, head and neck, pancreas, breast, endometrium, esophagus, advanced cervical cancer, lymphomas, metastatic osteosarcoma, and others) for which first‐line therapy can potentially include platinating agents.Ĭisplatin is associated with over 95% 5‐year survival rates in germ cell tumors, but can result in debilitating off target effects including ototoxicity, neurotoxicity, nephrotoxicity, and cardiometabolic abnormalities. Gene‐based analyses identified significant associations between tinnitus and WNT8A ( p = 2.5 × 10 −6), encoding a signaling protein important in germ cell tumors.Ĭisplatin and other platinating agents represent the most widely used and successful class of cytotoxic drugs worldwide. rs62283056 in WFS1 previously found to be significantly associated with hearing loss ( n = 511), was marginally significant in an independent replication cohort ( p = 0.06 n = 606). ![]() Hearing loss and TXNRD1, which plays a key role in redox regulation, showed borderline significance ( p = 4.2 × 10 −6) in gene‐based analysis. We observed positive associations between peripheral neuropathy and persistent vertigo, tobacco use, and excess alcohol consumption. Tinnitus was positively associated with tobacco use, hypercholesterolemia, and noise exposure. ![]() In addition, hearing loss was positively associated with BMIs at clinical evaluation and nonwork‐related noise exposure (>5 h/week). Survivors with these neurotoxicities experienced more hypertension and poorer self‐reported health. Hearing loss, tinnitus, and peripheral neuropathy, accounting for age and cisplatin dose, were interdependent. ![]()
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