Lauren Thomaier1, Burcu F Darst2, Patricia Jewett3, Cody Hoffmann4, Katherine Brown5, Aditi Makaram6, Anne Blaes3, Peter Argenta5, Deanna Teoh5, Rachel I Vogel5. 1. University of Minnesota, Division of Gynecologic Oncology, Minneapolis, MN, United States of America. Electronic address: thom7434@umn.edu. 2. University of Southern California, Center for Genetic Epidemiology, Keck School of Medicine, Los Angeles, CA, United States of America. 3. University of Minnesota, Division of Hematology and Oncology, Minneapolis, MN, United States of America. 4. University of Minnesota Genomics Center, University of Minnesota, Minneapolis, MN, United States of America. 5. University of Minnesota, Division of Gynecologic Oncology, Minneapolis, MN, United States of America. 6. University of Minnesota, College of Biological Sciences, Minneapolis, MN, United States of America.
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.
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.
Authors: Marta Seretny; Gillian L Currie; Emily S Sena; Sabrina Ramnarine; Robin Grant; Malcolm R MacLeod; Leslie A Colvin; Marie Fallon Journal: Pain Date: 2014-09-23 Impact factor: 6.961
Authors: Lara E Sucheston; Hua Zhao; Song Yao; Gary Zirpoli; Song Liu; William E Barlow; Halle C F Moore; G Thomas Budd; Dawn L Hershman; Warren Davis; Gregory L Ciupak; James A Stewart; Claudine Isaacs; Timothy J Hobday; Muhammad Salim; Gabriel N Hortobagyi; Julie R Gralow; Robert B Livingston; Kathy S Albain; Daniel F Hayes; Christine B Ambrosone Journal: Breast Cancer Res Treat Date: 2011-07-16 Impact factor: 4.872
Authors: D L Hertz; S Roy; A A Motsinger-Reif; A Drobish; L S Clark; H L McLeod; L A Carey; E C Dees Journal: Ann Oncol Date: 2013-02-14 Impact factor: 32.976
Authors: Patricia I Jewett; Deanna Teoh; Sue Petzel; Heewon Lee; Audrey Messelt; Jeffrey Kendall; Dorothy Hatsukami; Susan A Everson-Rose; Anne H Blaes; Rachel I Vogel Journal: JCO Oncol Pract Date: 2020-02-24
Authors: E A Calhoun; E E Welshman; C-H Chang; J R Lurain; D A Fishman; T L Hunt; D Cella Journal: Int J Gynecol Cancer Date: 2003 Nov-Dec Impact factor: 3.437
Authors: Luis J Leandro-García; Lucía Inglada-Pérez; Guillermo Pita; Elisabet Hjerpe; Susanna Leskelä; Carlos Jara; Xabier Mielgo; Anna González-Neira; Mercedes Robledo; Elisabeth Avall-Lundqvist; Henrik Gréen; Cristina Rodríguez-Antona Journal: J Med Genet Date: 2013-06-17 Impact factor: 6.318
Authors: Cynthia S Bonhof; Floortje Mols; M Caroline Vos; Johanna M A Pijnenborg; Dorry Boll; Gerard Vreugdenhil; Nicole P M Ezendam; Lonneke V van de Poll-Franse Journal: Gynecol Oncol Date: 2018-03-28 Impact factor: 5.482
Authors: William P Tew; Hyman B Muss; Gretchen G Kimmick; Vivian E Von Gruenigen; Stuart M Lichtman Journal: J Clin Oncol Date: 2014-08-20 Impact factor: 44.544