Effect of XPD and TP53 Gene Polymorphisms on the Risk of Platinum-Based Chemotherapy Induced Toxicity in Bangladeshi Lung Cancer Patients

• Published in: Asian Pacific journal of cancer prevention : APJCP Vol. 22; no. 12; pp. 3809 - 3815
• Main Authors: Nairuz, Tahsin, Bushra, Yearul Umme, Kabir, Yearul
• Format: Journal Article
• Language: English
• Published: Thailand West Asia Organization for Cancer Prevention 01.12.2021
• Subjects: Antineoplastic Agents - adverse effects; Bangladesh; Carboplatin - adverse effects; Cisplatin - adverse effects; Codon; Drug-Related Side Effects and Adverse Reactions - genetics; Female; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Male; Middle Aged; Pharmacogenomic Variants - genetics; Platinum Compounds - adverse effects; Polymorphism, Restriction Fragment Length; Tumor Suppressor Protein p53 - drug effects; Tumor Suppressor Protein p53 - genetics; Xeroderma Pigmentosum Group D Protein - drug effects; Xeroderma Pigmentosum Group D Protein - genetics; Bangladesh; platinum-based chemotherapy; Tp53; XPD; Lung cancer; Genetic polymorphism
• ISSN: 1513-7368; 2476-762X
• DOI: 10.31557/APJCP.2021.22.12.3809

Platinum-based drugs, including cisplatin and carboplatin, are the most active and extensively used agents for treating lung cancer. Genetic polymorphisms of DNA repair gene XPD and tumor suppressor gene TP53 are connected with alterations in enzyme activity. They may help explain interindividual differences in toxicity outcomes after platinum-based chemotherapy for lung cancer. Therefore, this study aimed to investigate XPD Lys751Gln and TP53 Arg72Pro polymorphisms on the risk of platinum-based chemotherapy-induced toxicity in lung cancer patients in the Bangladeshi population. Study subjects comprised of 180 platinum-based chemotherapy treated histologically confirmed lung cancer patients. Genetic polymorphisms of XPD were ascertained by Polymerase Chain Reaction-based Restriction Fragment Length Polymorphism (PCR-RFLP), while TP53 genotypes were analyzed using the multiplex PCR-based method. Toxicity was assessed based on the Common Terminology Criteria for Adverse Events (CTCAE v5.0). From the results, there was no significant association observed between grade 1-2 or grade 3-4 platinum-based chemotherapy induced toxicities like anemia and XPD codon 751 (Lys/Gln: OR=1.40, 95% CI=0.75-2.64, p>0.05; Gln/Gln: OR=1.07, 95% CI=0.45-2.52, p>0.05 and Lys/Gln+Gln/Gln: OR=1.31, 95% CI=0.73-2.38, p>0.05) or TP53 codon 72 genetic polymorphisms (Arg/Pro: OR=0.64, 95% CI=0.34-1.17, p>0.05; Pro/Pro: OR=0.46, 95% CI=0.15-1.42, p>0.05 and Arg/Pro+Pro/Pro: OR=0.62, 95% CI=0.34-1.15, p>0.05). Similar results were found between neutropenia, leukopenia, thrombocytopenia and gastrointestinal toxicities and XPD Lys751Gln or TP53 Arg72Pro genetic polymorphisms. These findings indicated that no significant association was found between either XPD codon 751 or TP53 codon 72 genetic polymorphisms and platinum-based chemotherapy-related toxicities in Bangladeshi lung cancer patients.