BACKGROUND: The insulin-like growth factor 1 (IGF1) pathway is deeply involved in cell proliferation, including tumorigenesis. Aberrant genetic alterations of IGF1 pathway members were revealed in certain malignancies, including chondrosarcoma (CHS). We proposed that genetic polymorphisms in IGF1 pathways might be associated with susceptibility to tumorigenesis and prognosis of CHS in Chinese populations.

MATERIAL AND METHODS: We recruited 112 pathologically diagnosed CHS cases and 104 cancer-free controls in this study. There were 5 single-nucleotide polymorphisms of IGF1 pathway members (IGF1R rs2016347, IGF1 rs1520220, IGF1 rs2946834, IGF3BP3 rs2270628, and IGF2 rs4320932) genotyped that subsequently underwent bioinformatic analyses. DNA from validated CHS cases was extracted from frozen blood samples preserved in liquid nitrogen, while DNA from tumor-free controls was extracted from fresh blood. SNP genotyping was conducted by PCR.

RESULTS: The variant T allele of IGF1R (rs2016347) is potentially correlated with poor outcome in patients with conventional CHS. The GT and TT genotypes of IGF1R rs2016347 predicted statistically significant higher risk of tumor metastasis and higher histological grade of CHS.

CONCLUSIONS: We hypothesized that IGF1 member polymorphisms are associated with chondrosarcoma. We found that genetic polymorphisms in IGF1 pathway members are associated with elevated risk and poor prognosis of conventional CHS patients in Chinese populations. IGF1R rs2016347 polymorphisms were associated with the risk of lung metastasis of CHS. The IGF1 pathway members do not appear to be involved in the tumorigenesis of CHS.

Keywords: Chondrosarcoma, Polymorphism, Genetic, Alleles, Asians, Genotype, Haplotypes, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Insulin-Like Growth Factor II, Polymorphism, Single Nucleotide, Risk Factors