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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)578-582
Number of pages5
JournalGynecologic oncology
Volume163
Issue number3
Early online dateOct 18 2021
DOIs
StatePublished - Dec 2021

Bibliographical note

Funding Information:
This research was supported by the National Institutes of Health (P30 CA77598, UL1TR002494), a University of Minnesota Grant-in-Aid Award and the Masonic Cancer Center, University of Minnesota . RIV is supported by a Department of Defense Ovarian Cancer Research Program Ovarian Cancer Academy Early Career Investigator Award ( OC180392 W81XWH-19-1-0013 ).

Publisher Copyright:
© 2021 Elsevier Inc.

Keywords

  • Chemotherapy
  • Chemotherapy induced peripheral neuropathy
  • Gynecologic cancer
  • Gynecologic cancer survivors
  • Neuropathy

PubMed: MeSH publication types

  • Journal Article
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

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