Association of C-Reactive Protein (CRP) Gene Polymorphisms, Serum CRP Levels and Cervical Cancer Prognosis

Background: C-reactive protein (CRP) is the prototypical biomarker of inflammation. Genetic variations within the CRP gene have been shown to be associated with alterations of CRP expression and prognosis in cancer patients. The purpose of this study was to evaluate the association between four polymorphisms of the CRP gene, CRP serum levels, clinicopathological parameters of cervical cancer and survival in patients with cervical cancer. Materials and Methods: The four most common single nucleotide gene polymorphisms CRP1919 (rs1417938), CRP2667 (rs1800947), CRP3872 (rs1205), and CRP5237 (rs2808630) were evaluated in 178 patients with cervical cancer. DNA was extracted from blood samples and CRP gene polymorphisms were investigated, using pyrosequencing. Findings were correlated with CRP serum levels, clinico-pathological parameters of cervical cancer, and disease-free and overall survival. Furthermore, the association between haplotype combinations and survival was investigated. Results: Presence of the CRP gene polymorphism CRP5237A>G was associated with lower CRP serum levels (p=0.04). Univariate survival analysis revealed that CRP1919T>A polymorphism (p=0.02), International Federation of Gynecology and Obstetrics stage (p<0.001), lymph node involvement (p=0.004), histological grade (p=0.01), and serum CRP levels (p<0.001) correlate with overall survival. In the multivariable Cox regression model, CRP1919T>A (p=0.02), tumor stage (p<0.001), lymph node involvement (p=0.03), patients' age (p=0.02), and serum CRP levels (p<0.001) were found to be independently associated with overall survival. None of the haplotype combinations were associated with prognosis of patients with cervical cancer. Conclusion: Presence of the CRP1919T>A polymorphism was associated with impaired overall survival in patients with cervical cancer. The CRP gene polymorphism CRP5237A>G was associated with decreased serum CRP levels.