Circulating IL-1beta levels, polymorphisms of IL-1B, and risk of cervical cancer in Chinese women

Abstract

Purpose: Long-term human papillomavirus (HPV) infection is a prerequisite for cervical cancer. IL-1beta and IL-1Ra expression levels play an important role in cervical carcinogenesis. Several functional genetic variants in IL1B and IL-RN have been reported to be associated with IL-1beta expression and cancer susceptibility. In the current study, we hypothesized that plasma IL-1beta levels, IL-1B and IL-RN polymorphisms were candidate biomarkers for cervical cancer.

Methods: We measured plasma IL-1beta levels and genotyped IL-1B and IL-RN polymorphisms in a case-control study of 404 cervical cancer cases and 404 controls in Chinese women.

Results: The mean plasma IL-1beta levels in cervical cancer cases (42.19 +/- 31.55 pg/ml) was significantly higher than those in controls (34.86 +/- 22.68 pg/ml, P = 0.0002), and plasma IL-1beta levels above the 75% quartiles in controls (IL-1beta > or = 46.94 pg/ml) were associated with a 1.74-fold significantly increased risk of cervical cancer [95% confidence interval (CI), 1.28-2.36], compared with those of lowest quartile. Multivariate logistic regression analyses revealed that the variant genotypes, IL-1B T-31C TC/CC and C-511T CT/TT, were associated with a significantly increased risk of cervical cancer [adjusted odds ratio (OR), 1.60; 95% CI, 1.16-2.21 for -31TC/CC, and adjusted OR, 1.52; 95% CI, 1.10-2.09 for -511CT/TT, respectively), especially among subjects having higher levels of IL-1beta. However, IL-RN VNTR polymorphism was not associated with cervical cancer risk in the current study. Furthermore, the significant differences of IL-1beta concentration between cervical cancer cases and controls were observed only among subjects carrying T-31C or C-511T variant genotypes.

Conclusion: Functional IL-1B genotypes may modify plasma IL-1beta concentrations to contribute to the etiology of cervical cancer in Chinese women; however, further perspective studies are warranted to test the causal effects of IL-1beta concentration in cervical carcinogenesis.