Genetic polymorphisms of GSTP1, XRCC1, XPC and ERCC1: prediction of clinical outcome of platinum-based chemotherapy in a
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ORIGINAL ARTICLE
Genetic polymorphisms of GSTP1, XRCC1, XPC and ERCC1: prediction of clinical outcome of platinum-based chemotherapy in advanced non-small cell lung cancer patients of Bangladesh Most. Umme Bushra1 · Sanzana Fareen Rivu2,3 · Ali Ehsan Sifat3 · Noor Ahmed Nahid3 · Maizbha Uddin Ahmed3 · Mir Md. Abdullah Al‑Mamun3 · Mohd Nazmul Hasan Apu3 · Md. Siddiqul Islam3 · Md. Reazul Islam3 · Mohammad Safiqul Islam4 · Abul Hasnat3 Received: 19 March 2020 / Accepted: 28 August 2020 © Springer Nature B.V. 2020
Abstract Inter-individual genetic makeup can trigger variability in platinum-based chemotherapeutic responses and corresponding adverse drug reactions and toxicities. Exploring the genetic causes behind these inter-individual variabilities in platinumbased chemotherapeutic responses by investigating the effects of GSTP1 (rs1695), XRCC1 (rs25487), XPC (rs2228001) and ERCC1 (rs11615) genetic polymorphisms on toxicity and therapeutic response of this treatment among Bangladeshi advanced non-small cell lung cancer (NSCLC) patients was the aim of this study. 285 Clinically proven either stage IIIB or IV (advanced) NSCLC patients aging not less than 18 years old and receiving platinum-based chemotherapy were recruited to assess the influence of these four single nucleotide polymorphisms (SNPs) on peripheral leukocytes. Toxicity and response were evaluated by multivariate regression analyses using SPSS statistical software (version 17.0). XRCC1 (rs25487) polymorphism was found to act as a predictive factor for not only grade 3 and 4 anemia (p = 0.008), neutropenia (p = 0.010), thrombocytopenia (p = 0.025) and gastrointestinal toxicity (p = 0.002) but also for therapeutic response (p = 0.012) in platinum-based chemotherapy. Although GSTP1 (rs1695) polymorphism might serve as prognostic factor regarding grade 3 or 4 neutropenia, a significant (p = 0.044) improvement in response to platinum-based chemotherapy was observed. However, XPC (rs2228001) and ERCC1 (rs11615) polymorphisms could not establish any significant relation with toxicity or therapeutic response. XRCC1 (rs2228001) and GSTP1 (rs1695) polymorphisms might explain platinum-induced clinical outcomes in terms of both toxicity and therapeutic response variations among Bangladeshi advanced NSCLC patients. Keywords Non-small cell lung cancer · GSTP1 · XRCC1 · XPC · ERCC1 · Polymorphism
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11033-020-05771-2) contains supplementary material, which is available to authorized users. * Mohammad Safiqul Islam [email protected] 1
Department of Pharmacy, Manarat International University, Khagan, Savar, Dhaka 1343, Bangladesh
2
Department of Pharmacy, East West University, Aftabnagar, Dhaka 1212, Bangladesh
3
Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh
4
Department of Pharmacy, Noakhali Science and Technology University, Sonapur, Noakhali 3814, Bangladesh
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