Genetic variants associated with post-traumatic stress symptoms in patients with gynecologic cancer.

OBJECTIVE: Patients with cancer experience symptoms of post-traumatic stress disorder (PTSD) more commonly than the general population. The objective of this study was to identify single nucleotide polymorphisms (SNPs) associated with increased risk of post-traumatic stress disorder (PTSD) in patients with gynecologic cancer. METHODS: A prospective cohort study recruited 181 gynecologic cancer survivors receiving care at the University of Minnesota between 2017 and 2020 who completed PTSD DSM-V surveys to self-report their symptoms of PTSD and provided saliva samples. DNA samples were genotyped for 11 SNPs in 9 genes involved in dopaminergic, serotonergic, and opioidergic systems previously associated with risk of PTSD in populations without cancer. RESULTS: Most participants had either ovarian (42.5%) or endometrial (46.4%) cancer; fewer had cervical (7.7%) or vaginal/vulvar (3.3%) cancer. Two SNPS were identified as statistically significantly associated with higher PTSD scores: rs622337 in HTR2A and rs510769 in OPRM1. CONCLUSIONS: Genetic variation likely plays a role in development of PTSD. HTR2A is involved in the serotonin pathway, and OPRM1 is involved in the opioid receptor pathway. This information can be used by oncologic providers to identify patients at greater risk of developing PTSD and may facilitate referral to appropriate consultants and resources early in their treatment.

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

OBJECTIVE: To identify genetic variants associated with chemotherapy-induced peripheral neuropathy (CIPN) symptoms among gynecologic cancer survivors and determine the variants' predictive power in addition to age and clinical factors at time of diagnosis. METHODS: Participants of a prospective cohort study on gynecologic cancers provided a DNA saliva sample and reported CIPN symptoms (FACT/GOG-Ntx). Genotyping of 23 single nucleotide polymorphisms (SNPs) previously identified as related to platinum- or taxane-induced neuropathy was performed using iPLEX Gold method. Risk allele carrier frequencies of 19 SNPs that passed quality checks were compared between those with/without high CIPN symptoms using logistic regression, adjusting for age. Receiver operating characteristic (ROC) curves using clinical risk factors (age, diabetes, BMI, Charlson Comorbidity Index, previous cancer diagnosis) with and without the identified SNPs were compared. RESULTS: 107 individuals received platinum or taxane-based chemotherapy and provided sufficient DNA for analysis. Median age was 65.1 years; 39.6% had obesity and 8.4% diabetes; most had ovarian (58.9%) or uterine cancer (29.0%). Two SNPs were significantly associated with high CIPN symptomatology: rs3753753 in GPX7, OR = 2.55 (1.13, 5.72) and rs139887 in SOX10, 2.66 (1.18, 6.00). Including these two SNPs in a model with clinical characteristics led to an improved AUC for CIPN symptomatology (0.65 vs. 0.74, p = 0.04). CONCLUSIONS: Genetic and clinical characteristics were predictive of higher CIPN symptomatology in gynecologic cancer survivors, and combining these factors resulted in superior predictive power compared with a model with clinical factors only. Prospective validation and assessment of clinical utility are warranted.