دورية أكاديمية
أعرض في EDS

Association between Genetic Variants and Peripheral Neuropathy in Patients with NSCLC Treated with First-Line Platinum-Based Therapy.

التفاصيل البيبلوغرافية
العنوان: Association between Genetic Variants and Peripheral Neuropathy in Patients with NSCLC Treated with First-Line Platinum-Based Therapy.
المؤلفون: de Jong C; Department of Clinical Pharmacy, Division of Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.; Department of Clinical Pharmacy, St. Antonius Hospital, 3430 EM Nieuwegein, The Netherlands., Herder GJM; Department of Pulmonology, Meander Medical Center, 3813 TZ Amersfoort, The Netherlands., van Haarlem SWA; Department of Pulmonology, St Antonius Hospital, 3430 EM Nieuwegein, The Netherlands., van der Meer FS; Department of Pulmonology, Diakonessenhuis, 3582 KE Utrecht, The Netherlands., van Lindert ASR; Department of Pulmonology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands., Ten Heuvel A; Department of Pulmonology, Groene Hart Hospital, 2803 HH Gouda, The Netherlands., Brouwer J; Department of Pulmonology, Rivierenland Hospital, 4002 WP Tiel, The Netherlands., Egberts TCG; Department of Clinical Pharmacy, Division of Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands., Deneer VHM; Department of Clinical Pharmacy, Division of Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
المصدر: Genes [Genes (Basel)] 2023 Jan 07; Vol. 14 (1). Date of Electronic Publication: 2023 Jan 07.
نوع المنشور: Multicenter Study; Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101551097 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4425 (Electronic) Linking ISSN: 20734425 NLM ISO Abbreviation: Genes (Basel) Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel : MDPI
مواضيع طبية MeSH: Carcinoma, Non-Small-Cell Lung*/drug therapy , Carcinoma, Non-Small-Cell Lung*/genetics , Lung Neoplasms*/drug therapy , Lung Neoplasms*/genetics , Peripheral Nervous System Diseases*/chemically induced , Peripheral Nervous System Diseases*/genetics, Humans ; Platinum/adverse effects ; Prospective Studies ; Follow-Up Studies
مستخلص: Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, disabling side effect in non-small cell lung cancer (NSCLC) patients treated with platinum-based therapy. There is increasing evidence for associations between genetic variants and susceptibility to CIPN. The aim of this study was to further explore genetic risk factors for CIPN by investigating previously reported genetic associations. Methods: A multicenter prospective follow-up study (PGxLUNG, NTR NL5373610015) in NSCLC patients (stage II-IV) treated with first-line platinum-based (cisplatin or carboplatin) chemotherapy was conducted. Clinical evaluation of neuropathy (CTCAE v4.03) was performed at baseline and before each cycle (four cycles, every three weeks) of chemotherapy and at three and six months after treatment initiation. The relationship between 34 single nucleotide polymorphisms (SNPs) in 26 genes and any grade (grade ≥ 1) and severe (grade ≥ 2) CIPN was assessed by using univariate and multivariate logistic regression modelling. Results: In total, 320 patients were included of which 26.3% (n = 84) and 8.1% (n = 26) experienced any grade and severe CIPN, respectively. The GG-genotype (rs879207, A > G) of TRPV1, a gene expressed in peripheral sensory neurons, was observed in 11.3% (n = 36) of the patients and associated with an increased risk of severe neuropathy (OR 5.2, 95%CI 2.1−12.8, adjusted p-value 0.012). A quarter (25%, n = 9/36) of the patients with the GG-genotype developed severe neuropathy compared to 6% (n = 17/282) of the patients with the AG- or AA-genotype. Multivariate logistic regression analysis showed statistically significant associations between the GG-genotype (ORadj 4.7, 95%CI 1.8−12.3) and between concomitant use of paclitaxel (ORadj 7.2, 95%CI 2.5−21.1) and severe CIPN. Conclusions: Patients with the GG-genotype (rs879207) of TRPV1 have an almost 5-fold higher risk of developing severe neuropathy when treated with platinum-based therapy. Future studies should aim to validate these findings in an independent cohort and to further investigated the individualization of platinum-based chemotherapy in clinical practice.
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فهرسة مساهمة: Keywords: chemotherapy-induced peripheral neuropathy (CIPN); chemotherapy-induced toxicity; neurotoxicity; non-small cell lung cancer (NSCLC); platinum-based chemotherapy
سلسلة جزيئية: NTR NL5373610015
المشرفين على المادة: 49DFR088MY (Platinum)
تواريخ الأحداث: Date Created: 20230121 Date Completed: 20230124 Latest Revision: 20231117
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9858836
DOI: 10.3390/genes14010170
PMID: 36672910
قاعدة البيانات: MEDLINE
الوصف
تدمد:2073-4425
DOI:10.3390/genes14010170