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

• Published in: Molecular biology reports Vol. 47; no. 9; pp. 7073 - 7082
• Main Authors: Bushra, Most. Umme, Rivu, Sanzana Fareen, Sifat, Ali Ehsan, Nahid, Noor Ahmed, Ahmed, Maizbha Uddin, Al-Mamun, Mir Md. Abdullah, Apu, Mohd Nazmul Hasan, Islam, Md. Siddiqul, Islam, Md. Reazul, Islam, Mohammad Safiqul, Hasnat, Abul
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-09-2020; Springer Nature B.V
• Subjects: Aging; Animal Anatomy; Animal Biochemistry; Bangladesh; Biomedical and Life Sciences; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Chemotherapy; DNA-Binding Proteins - genetics; Endonucleases - genetics; ERCC1 protein; Female; Gene polymorphism; Glutathione S-Transferase pi - genetics; Glutathione transferase; Histology; Humans; Leukocytes; Life Sciences; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Middle Aged; Morphology; Neoplasm Proteins - genetics; Neutropenia; Non-small cell lung carcinoma; Original Article; Patients; Platinum; Platinum - administration & dosage; Platinum - adverse effects; Polymorphism; Polymorphism, Single Nucleotide; Predictive Value of Tests; Single-nucleotide polymorphism; Small cell lung carcinoma; Thrombocytopenia; Toxicity; X-ray Repair Cross Complementing Protein 1 - genetics; XPC protein; XRCC1 protein; Bangladesh; XRCC1; XPC; GSTP1; ERCC1; Non-small cell lung cancer; Polymorphism
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-020-05771-2

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 platinum-based 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.