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

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.

The Association of Polymorphisms in Nrf2 and Genes Involved in Redox Homeostasis in the Development and Progression of Clear Cell Renal Cell Carcinoma

“…Four haplotypes involving these two polymorphisms have been defined. Maniglia et al found haplotypes GSTP1A and GSTP1D having higher frequency among cases of head and neck squamous cell carcinoma than among controls [ 54 ]. Since the overall functions of GSTs also include the regulation of cell signaling, the GSTP1C haplotype has been considered a better c-Jun N-terminal kinase 1 inhibitor than the reference GSTP1A haplotype [ 32 ].…”

Gene polymorphisms and risk of head and neck squamous cell carcinoma: a systematic review

“…Maniglia, 2020 [15]; GSTT1 null Fernández-Mateos, 2019 [4]; Trizna, 1995 [7]; Jahnke, 1996 [8]; Cheng, 1999 [10]; Hanna, 2001 [11]; Gajecka, 2005 [12]; Ruwali, 2011 [13]; Yaghmaei, 2015 [14]; Maniglia, 2020 [15] GSTM3 A, B Jahnke, 1996 [8]…”

“…In one study, A/G and A/G+ G/G genotypes of GSTP1 Ile105Val (rs1695) polymorphism were associated with significantly decreased risk of HNSCC [13]. In contrast, in other studies, there were not significant differences between the frequency of alleles and genotypes of this polymorphism between the HNSCC group and control group [4,[14][15][16]. The GA + GG genotypes of this polymorphism were significantly higher in heavy smoking HNSCC patients compared to non-smokers and light-smokers and were associated with HNSCC risk in a tobacco dose-dependent manner [16].…”

“…Fernández-Mateos, 2019 [4]; Ruwali, 2011 [13]; Yaghmaei, 2015 [14]; Maniglia, 2020 [15]; Cho, 2006 [16] C341T Maniglia, 2020 [15] CYP2D6 *1, * Fernández-Mateos, 2019 [4]; Sturgis, 1999 [19]; Olshan, 2002 [20]; Gajecka, 2005 [21]; Kietthubthew, 2006 [22]; Costa, 2016 [23] Arg399Gln Fernández-Mateos, 2019 [4]; Sturgis, 1999 [19]; Olshan, 2002 [20]; Gajecka, 2005 [21]; Kietthubthew, 2006 [22]; Costa, 2016 [23];…”

Gene polymorphisms and prognosis of head and neck squamous cell carcinoma: a systematic review

“…In general, different gene polymorphisms of glutathione-S-transferases ( GST s), including GSTM1 deletion , GSTT1 deletion , GSTP1 rs1695 and GSTP1 rs749174 , were not associated with survival in HNSCCs [ 14 , 34 , 63 , 68 , 71 ]. In one study, the non-null variant of GSTT1 deletion polymorphism was significantly associated with poor OS and DSS [ 14 ].…”