POLYMORPHISM AND CIRCULATING LEVELS OF IGF-1, IGF-1R, AND IGF-BP3 AMONG PROSTATE CANCER PATIENTS IN LAGOS STATE, NIGERIA
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Prostate cancer (PCa) is the most prevalent cancer in sub-Saharan Africa, with over 77,000 new cases annually, and Nigeria accounting for approximately 30,000 of these cases. The insulin-like growth factor (IGF) pathway, crucial for cellular proliferation and apoptosis, is implicated in cancer progression, including PCa. Elevated plasma IGF-1 levels are associated with PCa progression, whereas increased levels of IGF binding protein 3 (IGF-BP3) may reduce PCa risk. Genetic variations in IGF-1, such as the C-T haplotype, are linked to poorer survival in PCa patients with bone metastases. This study aims to examine single nucleotide polymorphisms (SNPs) in the IGF-1 and IGF-1R genes and their relationship to plasma levels of IGF-1, IGF-1R, and IGF-BP3, and the risk of PCa among men in Lagos State. The case-control study consisted of 75 PCa patients and 75 paired healthy controls. Plasma levels of IGF-1, IGF-1R, and IGF-BP3 were measured using enzyme-linked immunosorbent assay (ELISA), and SNP genotyping (IGF-1: rs6219, rs6220, rs5742694; IGF-1R: rs2229765) was performed using TaqMan assay. No overall statistical difference was found in plasma levels of IGF-1, IGF-BP3, and IGF-1R between cases and controls, although the IGF-1/IGF-BP3 molar ratio was higher in PCa patients (42.67) compared to controls (19.04), indicating increased level of bioavailable IGF-1 in PCa patients. Chi-square analysis revealed a strong positive association (OR: 9.1; p: 0.026) between the A/A genotype of IGF-1R SNP (rs2229765 (A/G)) and PCa, suggesting that individuals with this genotype are more likely to develop PCa. Significant differences in IGF-1R and IGF-1 levels were observed for specific genotypes of rs5742694 and rs2229765 SNPs. In conclusion, genetic polymorphisms in IGF-1R and IGF-1 are associated with differential protein levels in PCa cases versus controls, indicating potential risk and protective factors in Nigerian men.
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QD Chemistry, QH Natural history, RA Public aspects of medicine