预测 HIV 感染期间的癌症风险：炎症和凝血生物标志物的作用。
Predicting risk of cancer during HIV infection: the role of inflammatory and coagulation biomarkers.
机构信息
Department of Infectious Diseases, Rigshospitalet and Copenhagen HIV Programme, University of Copenhagen, Copenhagen, Denmark.
出版信息
AIDS. 2013 Jun 1;27(9):1433-41. doi: 10.1097/QAD.0b013e32835f6b0c.
OBJECTIVE
To investigate the relationship between inflammatory [interleukin-6 (IL-6) and C-reactive protein (CRP)] and coagulation (D-dimer) biomarkers and cancer risk during HIV infection.
DESIGN
A prospective cohort.
METHODS
HIV-infected patients on continuous antiretroviral therapy (ART) in the control arms of three randomized trials (N=5023) were included in an analysis of predictors of cancer (any type, infection-related or infection-unrelated). Hazard ratios for IL-6, CRP and D-dimer levels (log2-transformed) were calculated using Cox models stratified by trial and adjusted for demographics and CD4+ cell counts and adjusted also for all biomarkers simultaneously. To assess the possibility that biomarker levels were elevated at entry due to undiagnosed cancer, analyses were repeated excluding early cancer events (i.e. diagnosed during first 2 years of follow-up).
RESULTS
During approximately 24,000 person-years of follow-up (PYFU), 172 patients developed cancer (70 infection-related; 102 infection-unrelated). The risk of developing cancer was associated with higher levels (per doubling) of IL-6 (hazard ratio 1.38, P<0.001), CRP (hazard ratio 1.16, P=0.001) and D-dimer (hazard ratio 1.17, P=0.03). However, only IL-6 (hazard ratio 1.29, P=0.003) remained associated with cancer risk when all biomarkers were considered simultaneously. Results for infection-related and infection-unrelated cancers were similar to results for any cancer. Hazard ratios excluding 69 early cancer events were 1.31 (P=0.007), 1.14 (P=0.02) and 1.07 (P=0.49) for IL-6, CRP and D-dimer, respectively.
CONCLUSION
Activated inflammation and coagulation pathways are associated with increased cancer risk during HIV infection. This association was stronger for IL-6 and persisted after excluding early cancer. Trials of interventions may be warranted to assess whether cancer risk can be reduced by lowering IL-6 levels in HIV-positive individuals.
目的
探讨炎症标志物[白细胞介素-6（IL-6）和 C 反应蛋白（CRP）]和凝血标志物（D-二聚体）与 HIV 感染期间癌症风险的关系。
设计
前瞻性队列研究。
方法
在三项随机试验的对照臂中，纳入了正在接受连续抗逆转录病毒治疗（ART）的 HIV 感染患者（N=5023），以分析癌症（任何类型、感染相关或感染无关）的预测因素。使用 Cox 模型计算了 IL-6、CRP 和 D-二聚体水平（log2 转换）的风险比，模型按试验分层，并根据人口统计学数据、CD4+细胞计数以及所有生物标志物进行了调整。为了评估由于未确诊的癌症而导致生物标志物水平在入组时升高的可能性，分析中排除了早期癌症事件（即随访的前 2 年内诊断出的癌症）。
结果
在大约 24000 人年的随访期间（PYFU），172 名患者发生了癌症（70 例与感染相关，102 例与感染无关）。癌症发病风险与更高的 IL-6（风险比 1.38，P<0.001）、CRP（风险比 1.16，P=0.001）和 D-二聚体（风险比 1.17，P=0.03）水平相关。然而，当同时考虑所有生物标志物时，只有 IL-6（风险比 1.29，P=0.003）与癌症风险相关。与任何癌症相关的感染相关和感染无关的癌症结果相似。排除 69 例早期癌症事件后，IL-6、CRP 和 D-二聚体的风险比分别为 1.31（P=0.007）、1.14（P=0.02）和 1.07（P=0.49）。
结论
在 HIV 感染期间，激活的炎症和凝血途径与癌症风险增加相关。这种关联在 IL-6 中更强，并且在排除早期癌症后仍然存在。可能需要进行干预试验，以评估降低 HIV 阳性个体的 IL-6 水平是否可以降低癌症风险。
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