Abstract

Advanced head and neck squamous cell carcinoma (HNSCC) patients have been treated with cisplatin (CDDP) chemoradiation, and the variability of treatment effects has been attributed to single nucleotide variants (SNVs) in genes of metabolic pathways. This study investigated the roles of GSTM1, GSTT1, GSTP1 c.313A>G, XPC c.2815A>C, XPD c.934G>A and c.2251A>C, XPF c.2505T>C, ERCC1 c.354C>T, MLH1 c.93G>A, MSH2 c.211+9C>G, MSH3 c.3133G>A, EXO1 c.1765G>A, TP53 c.215G>C, CASP3 c.-1191A>G and c.-182-247G>T, FAS c.-1378G>A and c.-671A>G and FASL c.-844C>T SNVs in outcome of 109 patients treated with CDDP chemoradiation. Genotypes were identified in genomic DNA by PCR-based methods. Conventional criteria and tests analyzed response and survival. Patients with XPC c.2815AC or CC had 3.43 times more chances of presenting partial response or stable disease. Patients with FAS c.-671GG, GSTM1 present plus XPC c.2815AA, or plus XPD c.934GG, or plus XPD c.2251AA, or plus TP53 c.215GC or CC, and XPD c.2251AA plus XPF c.2505TT had up to 2.70 and 2.37 times more chances of presenting tumor progression and evolving to death, respectively. Our data indicate, for the first time, preliminary evidence that combined SNVs of CDDP metabolism act as independent prognostic factors and can be used to select patients for distinct treatments.

Details

Title
Genetic variability in cisplatin metabolic pathways and outcome of locally advanced head and neck squamous cell carcinoma patients
Author
Ferreira, Ana Maria Castro 1 ; Altemani, João Maurício Carrasco 2 ; Macedo, Ligia Traldi 1 ; Lourenço, Gustavo Jacob 1 ; Lima, Carmen Silvia Passos 3 

 University of Campinas, Laboratory of Cancer Genetics, Faculty of Medical Sciences, Campinas, Brazil (GRID:grid.411087.b) (ISNI:0000 0001 0723 2494) 
 University of Campinas, Department of Anesthesiology, Oncology and Radiology, Faculty of Medical Sciences, Campinas, Brazil (GRID:grid.411087.b) (ISNI:0000 0001 0723 2494) 
 University of Campinas, Laboratory of Cancer Genetics, Faculty of Medical Sciences, Campinas, Brazil (GRID:grid.411087.b) (ISNI:0000 0001 0723 2494); University of Campinas, Department of Anesthesiology, Oncology and Radiology, Faculty of Medical Sciences, Campinas, Brazil (GRID:grid.411087.b) (ISNI:0000 0001 0723 2494) 
Pages
16762
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2873111298
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.