血清细胞因子和趋化因子与前瞻性类风湿关节炎队列中癌症发病风险的关联。
Associations of serum cytokines and chemokines with the risk of incident cancer in a prospective rheumatoid arthritis cohort.
机构信息
VA Nebraska-Western Iowa Healthcare System, Omaha, NE, USA; Division of Rheumatology & Immunology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Division of Rheumatology & Immunology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
出版信息
Int Immunopharmacol. 2021 Aug;97:107719. doi: 10.1016/j.intimp.2021.107719. Epub 2021 Apr 29.
OBJECTIVES
We aimed to assess whether serum cytokine/chemokine concentrations predict incident cancer in RA patients.
METHODS
Data from cancer-free enrollees in the Veterans Affairs Rheumatoid Arthritis (VARA) Registry were linked to a national VA oncology database and the National Death Index (NDI) to identify incident cancers. Seventeen serum cytokines/chemokines were measured from enrollment serum and an overall weighted cytokine/chemokine score (CK score) was calculated. Associations of cytokines/chemokines with all-site, lung, and lymphoproliferative cancers were assessed in Cox regression models accounting for relevant covariates including age, sex, RA disease activity, and smoking.
RESULTS
In 1216 patients, 146 incident cancers (42 lung and 23 lymphoproliferative cancers) occurred over 10,072 patient-years of follow-up with a median time of 4.6 years from enrollment (cytokine/chemokine measurement) to cancer incidence. In fully adjusted models, CK score was associated with a higher risk of all-site (aHR 1.32, 95% CI 1.01-1.71, p < 0.001), lung (aHR 1.81, 1.40-2.34, p = 0.001), and lung/lymphoproliferative (aHR 1.54 [1.35-1.75], p < 0.001) cancer. The highest quartile of CK score was associated with a higher risk of all-site (aHR 1.91, 0.96-3.81, p = 0.07; p-trend = 0.005), lung (aHR 8.18, 1.63-41.23, p = 0.01; p-trend < 0.001), and lung/lymphoproliferative (aHR 4.56 [1.84-11.31], p = 0.001; p-trend < 0.001) cancer. Thirteen of 17 individual analytes were associated with incident cancer risk.
CONCLUSION
Elevated cytokine/chemokine concentrations are predictive of future cancer in RA patients, particularly lung and lymphoproliferative cancers. These results suggest that the measurement of circulating cytokines/chemokines could be informative in cancer risk stratification and could provide insight into future cancer prevention strategies in RA, and possibly individuals without RA.
目的
评估血清细胞因子/趋化因子浓度是否可预测类风湿关节炎（RA）患者的癌症发病情况。
方法
从退伍军人事务部类风湿关节炎（VARA）登记处的无癌症患者中提取数据，将其与国家退伍军人事务部肿瘤学数据库和国家死亡索引（NDI）进行关联，以确定癌症发病情况。从入组时的血清中检测了 17 种血清细胞因子/趋化因子，并计算了总体加权细胞因子/趋化因子评分（CK 评分）。采用 Cox 回归模型评估细胞因子/趋化因子与所有部位、肺部和淋巴增生性癌症之间的相关性，这些模型考虑了年龄、性别、RA 疾病活动度和吸烟等相关协变量。
结果
在 1216 例患者中，有 146 例发生癌症（42 例肺癌和 23 例淋巴增生性癌症），中位随访时间为 10072 患者年，从入组（细胞因子/趋化因子检测）到癌症发病的中位时间为 4.6 年。在完全调整的模型中，CK 评分与所有部位（校正危害比 [aHR] 1.32，95%置信区间 [CI] 1.01-1.71，p<0.001）、肺部（aHR 1.81，1.40-2.34，p=0.001）和肺部/淋巴增生性（aHR 1.54[1.35-1.75]，p<0.001）癌症的发病风险增加有关。CK 评分最高四分位数与所有部位（aHR 1.91，0.96-3.81，p=0.07；p 趋势=0.005）、肺部（aHR 8.18，1.63-41.23，p=0.01；p 趋势<0.001）和肺部/淋巴增生性（aHR 4.56[1.84-11.31]，p=0.001；p 趋势<0.001）癌症的发病风险增加有关。17 种分析物中有 13 种与癌症发病风险有关。
结论
升高的细胞因子/趋化因子浓度可预测 RA 患者未来的癌症发病风险，尤其是肺癌和淋巴增生性癌症。这些结果表明，循环细胞因子/趋化因子的测量可能有助于癌症风险分层，并可能为 RA 患者以及可能没有 RA 的个体的未来癌症预防策略提供新的见解。
Zotero 插件