Taxane treatment outcomes in histologically characterized Algerian lung cancer patients: a population-specific exploratory study of CYP3A4, CYP2C8, and ABCG2 variants

Taxane-based chemotherapy remains a cornerstone of lung cancer treatment, but its clinical use is often limited by dose-dependent toxicities, particularly peripheral neuropathy. In this retrospective study of 110 Algerian patients with lung cancer, we evaluated the influence of germline polymorphisms, distinct from tumor somatic alterations, on treatment outcomes, while considering World Health Organization classified histological subtypes. Based on their roles in taxane metabolism and transport, CYP2C8, CYP3A4, and ABCG2 were selected for analysis. Germline polymorphisms CYP2C8 c.416G>A, CYP3A4 g.392A>G, and ABCG2 c.421C>A were genotyped using TaqMan PCR, and their associations with treatment response, adverse events, and dose mod-ifications were analyzed using SPSS, Epi Info 7, and R-Studio. The results showed that the CYP2C8 c.416G>A polymorphism was not significantly associated with chemotherapy response or neuropathy incidence. The ABCG2 c.421C>A polymorphism was not significantly associated with treatment efficacy or peripheral neuropathy, but it was related to cumulative taxane exposure. The CYP3A4 g.392A>G polymorphism was associated with increased peripheral neuropathy severity. Adenocarcinoma histology was also significantly associated with treatment response (p = 0.01), underscoring the value of integrating histopathological and pharmacogenetic factors. These population-specific findings support further investigation of pharmacogenetic stratification in larger lung cancer cohorts.