Department of Biotechnology, 29080Thapar Institute of Engineering & Technology, Patiala, India.
Department of Pulmonary Medicine, 29751Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.
Hum Exp Toxicol. 2021 Dec;40(12_suppl):S739-S752. doi: 10.1177/09603271211059496. Epub 2021 Nov 15.
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 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.
The polymorphism of GSTP1 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 () for the polymorphism showed a higher trend of median survival time (MST) as compared to the patients bearing the wild type of genotype ) (MST = 8.30 vs. 7.47, = 0.56). Based on toxicity profiling, we observed that lung cancer patients with the mutant genotype of GSTP1 had an increased risk of leukopenia (OR = 2.41; 95% CI = 1.39-4.18, = 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, = 0.03). Our data also showed that in small cell lung carcinoma (SCLC) patients' polymorphism of was associated with thrombocytopenia (χ2 test = 7.32, = 0.02).
Our results suggest that GSTP1 IleVal polymorphism could be a predictive biomarker for hematological toxicity, like leukopenia and anemia, but not thrombocytopenia or neutropenia.
谷胱甘肽 S-转移酶（GST）家族的 P1 同工酶中的遗传多态性被发现可以调节和改变 GSTP1 蛋白的酶活性，从而可能导致对铂类化疗的敏感性发生变化。我们研究了 GSTP1 多态性与接受铂类双化疗的印度北部晚期肺癌患者的总生存期、治疗反应以及血液学和非血液学毒性之间的关系。
通过聚合酶链反应-限制性片段长度多态性评估 GSTP1 印度北部肺癌患者的多态性。共有 682 例肺癌患者入组本研究，结果观察到携带突变等位基因（）的患者的中位生存时间（MST）较携带野生型基因型（）的患者有较高的趋势（MST=8.30 比 7.47，=0.56）。基于毒性分析，我们观察到 GSTP1 突变基因型的肺癌患者发生白细胞减少的风险增加（OR=2.41；95%CI=1.39-4.18，=0.001），而携带野生等位基因（Ile/Ile）的患者风险较低。我们的数据表明，杂合基因型（Ile/Val）的患者发生严重贫血的风险增加了 2.14 倍（OR=2.14，95%CI=0.97-4.62，=0.03）。我们的数据还表明，小细胞肺癌（SCLC）患者的 GSTP1 多态性与血小板减少症有关（卡方检验=7.32，=0.02）。
我们的研究结果表明，GSTP1 IleVal 多态性可能是预测血液学毒性（如白细胞减少和贫血）的生物标志物，但不是血小板减少或中性粒细胞减少的生物标志物。
