The Significance of SLC29A1 Gene Polymorphisms in Response to Gemcitabine-Based Chemotherapy in Metastatic NSCLC

Abstract Background: z accounts for 80%–85% of lung cancer, and gemcitabine is essential for treatment. SLC29A1, a transmembrane protein, binds to gemcitabine. Single-nucleotide polymorphisms (SNPs) in SLC29A1 genes may affect its pharmacokinetics. Objectives: To evaluate the impact of SLC29A1 gene polymorphism on gemcitabine response in patients with non-small-cell lung cancer (NSCLC). Materials and Methods: This is a cross-sectional study comprising 98 NSCLC patients aged 30–70 under gemcitabine-based chemotherapy. Demographic and clinical characteristics of the patients were collected. The response is assessed by evaluation criteria in solid tumors, and then, patients are classified as responders or non-responders. Chemotherapy side effects were assessed. Gene fragment corresponding to SLC29A1 rs760370 gene polymorphism was amplified using four primers. The genotyping was performed through amplification refractory mutation system polymerase chain reaction. Results: This study revealed that responsive patients had a mean tumor size of 34.6 ± 30.94 cm 2 , significantly lower than non-responsive patients. After four to six treatment cycles, responsive patients had a mean tumor size reduction of 11.82 ± 13.98 cm 2 , while non-responsive patients had a reduction of 15.31 ± 6.27 cm 2 . Females have more tumor size reduction. The most common side effects are vomiting, anemia, leukopenia, neutropenia, and nausea. The frequency of mutant homozygous genotype (GG) of SLC29A1 rs760370 was higher in non-responsive vs. responsive patients (14.58% vs. 8%) compared with the AA and AG genotypes and suggests that genes affect chemotherapy effectiveness, predicting its presence affects therapeutic plans of patients. Conclusion: Genetics impacts chemotherapy effectiveness, with SNPs in genes potentially affecting treatment plans and predicting disease outcomes.