Nanjing Medical University, China.
J Cancer Res Clin Oncol. 2010 May;136(5):709-16. doi: 10.1007/s00432-009-0710-5. Epub 2009 Nov 11.
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.
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.
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.
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.
长期的人乳头瘤病毒(HPV)感染是宫颈癌的先决条件。白细胞介素-1β(IL-1β)和白细胞介素-1受体拮抗剂(IL-1Ra)的表达水平在宫颈癌的发生中起着重要作用。已有研究报道,IL1B 和 IL-RN 中的几个功能性遗传变异与 IL-1β 的表达和癌症易感性有关。在本研究中,我们假设血浆 IL-1β 水平、IL-1B 和 IL-RN 多态性是宫颈癌的候选生物标志物。
我们在中国女性的病例对照研究中测量了 404 例宫颈癌病例和 404 例对照的血浆 IL-1β 水平,并对 IL-1B 和 IL-RN 多态性进行了基因分型。
宫颈癌病例的平均血浆 IL-1β 水平(42.19±31.55pg/ml)明显高于对照组(34.86±22.68pg/ml,P=0.0002),且对照组中高于第 75 百分位的血浆 IL-1β 水平(IL-1β≥46.94pg/ml)与宫颈癌的风险增加 1.74 倍显著相关[95%置信区间(CI),1.28-2.36],与最低四分位相比。多变量逻辑回归分析显示,IL-1B T-31C TC/CC 和 C-511T CT/TT 变异基因型与宫颈癌的发生风险显著相关[校正比值比(OR),1.60;95%CI,1.16-2.21 为-31TC/CC,校正 OR,1.52;95%CI,1.10-2.09 为-511CT/TT],尤其是在 IL-1β 水平较高的人群中。然而,在本研究中,IL-RN VNTR 多态性与宫颈癌风险无关。此外,仅在携带 T-31C 或 C-511T 变异基因型的受试者中观察到宫颈癌病例与对照组之间的 IL-1β 浓度存在显著差异。
功能性 IL-1B 基因型可能通过改变血浆 IL-1β 浓度来影响宫颈癌的病因;然而,需要进一步的前瞻性研究来检验 IL-1β 浓度在宫颈癌发生中的因果效应。