Genetic variants predictive of chemotherapy-induced peripheral neuropathy symptoms in gynecologic cancer survivors

Abstract

<h3>Objectives:</h3> Identifying gynecologic cancer patients at higher risk of chemotherapy-induced peripheral neuropathy (CIPN), a common and debilitating side effect of cancer treatment, could inform treatment decision-making and quality of life discussions. We sought to identify genetic variants associated with the prevalence of CIPN among gynecologic cancer survivors, and to determine if these variants added predictive power to a model including demographic and clinical factors. <h3>Methods:</h3> Patients were recruited from an academic gynecologic-oncology practice into a prospective cohort study. Participants included in this analysis provided a voluntary DNA saliva sample and self-reported CIPN symptoms (FACT/GOG-Ntx) along with other emotional, social and physical health items. Clinical and treatment data were abstracted from medical records. Genotyping of 23 single nucleotide polymorphisms (SNPs) in 15 genes identified in the literature as being related to platinum or taxane-induced neuropathy in other cancer populations was performed using iPLEX Gold method. The analyses were restricted to White females (97% of the cohort) and those who received chemotherapy. Risk allele carrier frequencies of individuals with and without high CIPN symptoms (FACT/GOG-Ntx score >9.5, median) were compared using logistic regression adjusting for age; odds ratios (OR) and 95% confidence intervals (CIs) are reported. We generated receiver operating characteristic (ROC) curves to examine the predictive ability of the identified significant SNPs along with known clinical risk factors (age, diabetes, body mass index (BMI), Charlson Comorbidity Index (CCI), previous cancer diagnosis) with regards to CIPN symptomatology. <h3>Results:</h3> A total of 108 individuals who provided a saliva sample with sufficient DNA for analysis received chemotherapy and were included in the analysis. Mean age was 62.8±10.5 years; 40.4% had obesity and 9% had diabetes. Most were diagnosed with ovarian cancer (58%) or uterine cancer (30%), and were not actively receiving treatment (76%). Having at least one risk allele in two SNPs was significantly associated with high CIPN symptomology: rs3753753 in <i>GPX7,</i> 2.65 (1.18, 5.92) and rs139887 in <i>SOX10,</i> 2.55 (1.14, 5.72). Further, including these SNPs in the predictive model improved the ROC curve area under the curve (AUC) over the demographic and clinical characteristics alone (AUC: 0.75 vs. 0.66, p=0.04; Figure 1). <h3>Conclusions:</h3> Genetic and clinical characteristics are predictive of higher CIPN symptomatology in gynecologic cancer survivors and combining these factors resulted in superior predictive power. Prospective validation of these results and assessment of their clinical utility are warranted.