GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms in outcomes of head and neck squamous cell carcinoma patients treated with cisplatin chemoradiation

Pincinato, Eder de Carvalho; Costa, Ericka Francislaine Dias; Lopes‐Aguiar, Leisa; Nogueira, Guilherme; Lima, Tathiane Regine Penna; Visacri, Marília Berlofa; Costa, Anna Paula Lourenço; Lourenço, Gustavo Jacob; Calonga, Luciane; Mariano, Fernanda Viviane; Altemani, Albina; Coutinho‐Camillo, Cláudia Malheiros; Chone, Carlos Takahiro; Ramos, Celso Darío; Altemani, João Maurício Carrasco; Moriel, Patrícia; Lima, Carmen Sílvia Passos

doi:10.1038/s41598-019-45808-6

Cited by 13 publications

(21 citation statements)

References 47 publications

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“…According to the data of Table 2, the association between late ototoxicity and the GSTP1 polymorphism is very controversial. Both the homozygous mutant [14,26,32] and the wild genotype [28,30,33] were associated with ototoxicity [26,28] or a protective effect [14,30,32,33], or no effect was found [23,27,29,31].…”

Section: Discussionmentioning

confidence: 98%

GSTM1 null and GSTT1 null: predictors of cisplatin-caused acute ototoxicity measured by DPOAEs

et al. 2020

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Preventing the ototoxicity caused by cisplatin is a major issue yet to be overcome. Useful preventive treatments will soon be available. Consequently, the next step is to filter out those patients who are more prone to develop ototoxicity. The aim of this study was to prospectively evaluate potential predictive markers of acute ototoxicity as determined by measures of distortion product otoacoustic emissions (DPOAEs). A total of 118 patients from our previous DPOAE analysis were put under evaluation. Ototoxic cases were divided according to unilateral (n = 45) or bilateral (n = 23) involvement. The clinicopathological characteristics, hearing test results, germline GSTT1, GSTM1, and GSTP1 polymorphisms, and common laboratory parameters were included in the new analysis. Univariate and multivariate statistical tests were applied. According to multivariate logistic regression, the only independent predictor of unilateral ototoxicity (vs. non-affected) was a GSTM1 null genotype (OR = 4.52; 95%CI = 1.3-16.3), while for bilateral damage, the GSTT1 null genotype (OR = 4.76; 1.4-16) was a predictor. The higher starting serum urea level was characteristic of bilateral ototoxicity; however, the only independent marker of bilateral (vs. unilateral) ototoxicity was the presence of GSTT1 null genotype (OR = 2.44; 1.23-4.85). Different processes, involving the GSTM1 and GSTT1 genotypes, respectively, govern the development of acute unilateral and bilateral ototoxicities. Further research is needed to clarify these processes. Based on the above findings, patients whom are at risk may be selected for otoprotective therapies. Key messages & The acute ototoxicity was determined by DPOAE in 118 testicular cancer patients. & GSTM1 null was the only marker of unilateral ototoxicity (vs. non-affected). & The only marker of bilateral hearing loss (vs. non-affected) was the GSTT1 null. & GSTT1 null was also the marker of bilateral vs. unilateral ototoxicity. & A high-risk group may be selected for new, individualized otoprotective treatment.

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Section: Discussionmentioning

confidence: 98%

GSTM1 null and GSTT1 null: predictors of cisplatin-caused acute ototoxicity measured by DPOAEs

et al. 2020

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“…It has been documented that those individuals carrying both the mutant alleles for the GSTP1 IIe 105 Val polymorphism are more susceptible to inflammatory symptoms. 33 The decrease in the activity of GSTP1 in lung cancer subjects harboring the heterozygous or mutant genotype may result in high exposure to platinum-based compounds and thus proportional increase towards drug toxicity because of reduced GSTP1 mediated catalyzed reactions, thus leading to reduced metabolism of platinum-based drugs.…”

Section: Discussionmentioning

confidence: 99%

GSTP1 Ile¹⁰⁵Val polymorphism among North Indian lung cancer patients treated using monotherapy and poly-pharmacy

2021

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Background Genetic polymorphism within the P1 isoenzyme of the Glutathione-S-Transferase (GST) family is found to modulate and alter the enzyme activity of GSTP1 protein and thus may result in a change of sensitivity to platinum-based chemotherapy. We investigated the relationship between GSTP1 Ile 105 Val polymorphisms and overall survival, treatment response, and for both hematological and non-hematological toxicity of advanced North Indian lung cancer patients undergoing platinum-based double chemotherapy. Methods The polymorphism of GSTP1 Ile 105 Val in North Indian lung cancer patients was assessed by polymerase chain reaction-restriction fragment length polymorphism. A total of 682 lung cancer patients were enrolled in the study, and it was observed that patients who were carrying both the mutant alleles ( Val/Val) for the GSTP1 polymorphism showed a higher trend of median survival time (MST) as compared to the patients bearing the wild type of genotype (Ile/Ile) (MST = 8.30 vs. 7.47, p = 0.56). Based on toxicity profiling, we observed that lung cancer patients with the mutant genotype of GSTP1 (Val/Val) had an increased risk of leukopenia (OR = 2.41; 95% CI = 1.39-4.18, p = 0.001) as compared to subjects carrying both copies of the wild alleles (Ile/Ile). Our data suggested that patients with heterozygous genotype (Ile/Val) had a 2.14-fold increased risk of developing severe anemia (OR = 2.14, 95% CI = 0.97-4.62, p = 0.03). Our data also showed that in small cell lung carcinoma (SCLC) patients' polymorphism of GSTP1 was associated with thrombocytopenia (χ2 test = 7.32, p = 0.02). Conclusions Our results suggest that GSTP1 Ile105Val polymorphism could be a predictive biomarker for hematological toxicity, like leukopenia and anemia, but not thrombocytopenia or neutropenia

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“…Moreover, during treatment, drug resistance may develop, necessitating higher doses to achieve former antitumor effects; however, higher doses may exaggerate severe side effects [ 21 ]. Accordingly, combination treatment with various drugs with distinct mechanisms is a therapeutic strategy that may potentiate the therapeutic efficacy of each drug [ 22 , 23 , 24 , 25 ]. In view of these problems, combined treatment with other anticancer agents is an effective strategy to overcome those limitations for clinical application.…”

Section: Discussionmentioning

confidence: 99%

Extract of Juniperus indica Bertol Synergizes with Cisplatin to Inhibit Oral Cancer Cell Growth via Repression of Cell Cycle Progression and Activation of the Caspase Cascade

et al. 2020

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Oral cancer—a type of head and neck cancer—is estimated to be the fifth most common cancer in Taiwan. However, efficacious therapies for oral cancer are still lacking due to drug resistance and recurrence. Consequently, the identification of new anticancer agents for clinical treatment is needed. Juniperus indica Bertol is a plant of the Juniperus genus often used as a treatment in traditional medicine due to its anti-inflammatory, antibacterial and diuretic functions. The biofunctions of Juniperus indica Bertol including its anticancer potential, have not been fully explored. As a result, the aim of this research was to investigate the anticancer activity of Juniperus indica Bertol extract (JIB extract) and determine whether JIB extract has synergistic effects with cisplatin in oral cancer. These results are the first to demonstrate that JIB extract exhibits anticancer capacity and synergizes with cisplatin to treat oral cancer. Our findings indicate that JIB extract has a potential to develop anticancer agent and chemo therapeutic adjuvant for oral cancer.

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GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms in outcomes of head and neck squamous cell carcinoma patients treated with cisplatin chemoradiation

Cited by 13 publications

References 47 publications

GSTM1 null and GSTT1 null: predictors of cisplatin-caused acute ototoxicity measured by DPOAEs

GSTM1 null and GSTT1 null: predictors of cisplatin-caused acute ototoxicity measured by DPOAEs

GSTP1 Ile¹⁰⁵Val polymorphism among North Indian lung cancer patients treated using monotherapy and poly-pharmacy

Extract of Juniperus indica Bertol Synergizes with Cisplatin to Inhibit Oral Cancer Cell Growth via Repression of Cell Cycle Progression and Activation of the Caspase Cascade

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GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms in outcomes of head and neck squamous cell carcinoma patients treated with cisplatin chemoradiation

Cited by 13 publications

References 47 publications

GSTM1 null and GSTT1 null: predictors of cisplatin-caused acute ototoxicity measured by DPOAEs

GSTM1 null and GSTT1 null: predictors of cisplatin-caused acute ototoxicity measured by DPOAEs

GSTP1 Ile105Val polymorphism among North Indian lung cancer patients treated using monotherapy and poly-pharmacy

Extract of Juniperus indica Bertol Synergizes with Cisplatin to Inhibit Oral Cancer Cell Growth via Repression of Cell Cycle Progression and Activation of the Caspase Cascade

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GSTP1 Ile¹⁰⁵Val polymorphism among North Indian lung cancer patients treated using monotherapy and poly-pharmacy