Glutathione S-transferase Polymorphisms in Head and Neck Squamous Cell Carcinoma Treated with Chemotherapy and/or Radiotherapy.

Mauricio Pereira Maniglia,Juliana Garcia De Oliveira-Cucolo,Érika Cristina Pavarino,Patrícia Matos Biselli-Chicote,Eny Maria Goloni-Bertollo,Anelise Russo,José Victor -Maniglia,Gabriela Helena Rodrigues-Fleming

doi:10.31557/apjcp.2020.21.6.1637

Abstract

Background/Aim:The Glutathione S-transferases (GSTs) are important carcinogen-metabolizing enzymes. Polymorphisms involved in these enzymes can modulate the development and treatment of head and neck cancer. To investigate the association of GSTs polymorphisms with head and neck cancer and risk factors, clinical-pathological features, and survival time of the patients treated with chemotherapy and/or radiotherapy. Methods:The GST gene polymorphisms were evaluated in 197 cases and 514 controls by PCR-RFLP-Polymerase Chain Reaction Restriction Fragment Length Polymorphism. Results:The GSTP-313 was associated with a decreased risk for HNSCC (p=0.050). The GSTP1 haplotype analysis revealed a higher frequency of the AC and AT haplotypes in the case group than in the control group (p=0.013 and p=0.019, respectively), and the opposite for G-C haplotype (p = 0.015). Yet, the different combinations between the genotypes were associated with an increased risk of cancer. The study showed no association between the polymorphisms and primary tumor site, clinical-pathological characteristics, treatment (chemotherapy and/or radiotherapy) and survival time of the patients. Conclusion:The GST polymorphisms combination showed an increased risk for carcinogenesis, and studies with larger casuistry can contribute to the clarification of the role in individual patient differences for the response to chemotherapy and/or radiotherapy and identify biomarkers of susceptibility.

Highlights

Head and neck cancer presents an estimated 834,860 new cases in the world for 2018/2019 and comprises a heterogeneous group of tumors that originate in the squamous cells of the upper digestive tract lining epithelium, including lip, oral cavity, nasal cavity, paranasal sinus, pharynx, larynx (IARC, 2019)
Considering the evidence presented, this study aimed to investigate the association of GSTM1 and GSTT1 null genotypes and single nucleotide polymorphisms (SNPs) A313G and C341T of the GSTP1 gene with head and neck cancer, as well as to verify the association between these polymorphisms and the anatomical site of tumor occurrence, clinical-pathological characteristics, relapse-free time and survival of patients with head and neck cancer treated with chemotherapy and/or radiotherapy
We evaluated the combined effect of the four polymorphisms studied (Table 2), an increase risk of head and neck squamous cell carcinoma (HNSCC) was observed in the presence of the duple combination: GSTT1 non-null/GSTM1 null genotypes (OR = 1.93; 95%CI: 1.15-3.24; p = 0.012), GSTP1-313AA/-341CT+TT

Summary

Introduction

Head and neck cancer presents an estimated 834,860 new cases in the world for 2018/2019 and comprises a heterogeneous group of tumors that originate in the squamous cells of the upper digestive tract lining epithelium, including lip, oral cavity, nasal cavity, paranasal sinus, pharynx, larynx (IARC, 2019). It is a multifactorial disease, influenced by age, gender, environmental factors such as smoking habits, alcohol consumption, HPV infection, genetic factors such as gene polymorphisms and exposure to radiation solar UVA (lips cancer) (Mirghani et al, 2017). GSTs act as inactivating enzymes for Phase I products/ mediated oxidative metabolism by cytochrome P450 and microsomal epoxide hydrolase, leading to hydrophilic metabolite capable of being excreted for homeostatic control and detoxification of lipophilic xenobiotics which occurs in the Phase III (Marchewka et al, 2017)

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