Abstract
BACKGROUND: Ovarian cancer (OC) remains the most lethal gynaecological malignancy, largely due to late-stage diagnosis, tumour heterogeneity, and high recurrence rates. The insulin-like growth factor-1 (IGF-1) axis has been implicated in tumour proliferation, survival, and treatment resistance. Yet, the prognostic relevance of its genetic variants in OC is not well established. The present study aims to evaluate the impact of two IGF-1-related single-nucleotide polymorphisms (SNPs), IGF1 rs6220 and IGF1R rs2016347, on the clinical outcome of 330 OC patients. METHODS AND RESULTS: SNP genotyping was performed using the TaqMan(®) Allelic Discrimination methodology. Regarding IGF1 rs6220, G allele carriers presented significantly improved overall survival compared with AA homozygotes within the subgroup of women undergoing suboptimal cytoreductive surgery (residual disease ≥ 1 cm) (p = 0.039). As for IGF1R rs2016347, the TT genotype was associated with shorter disease-free survival than A allele carriers within the well-differentiated tumour group (p = 0.028). CONCLUSIONS: These results indicate a context-dependent impact of IGF-1 axis polymorphisms on OC prognosis, suggesting their potential utility as molecular markers. Further validation in larger, independent cohorts, together with functional studies, is warranted to confirm these results and clarify the biological mechanisms underlying the influence of IGF-1-related genetic variants on OC behaviour.