Predicting risk of cancer during HIV infection: the role of inflammatory and coagulation biomarkers

TY - JOUR

T1 - Predicting risk of cancer during HIV infection

T2 - the role of inflammatory and coagulation biomarkers

AU - Borges, Álvaro H

AU - Silverberg, Michael J

AU - Wentworth, Deborah

AU - Grulich, Andrew E

AU - Fätkenheuer, Gerd

AU - Mitsuyasu, Ronald

AU - Tambussi, Giuseppe

AU - Sabin, Caroline A

AU - Neaton, James D

AU - Lundgren, Jens D

AU - INSIGHT SMART

PY - 2013/6/1

Y1 - 2013/6/1

N2 - 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.

AB - 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.

KW - Adult

KW - C-Reactive Protein

KW - Cohort Studies

KW - Female

KW - Fibrin Fibrinogen Degradation Products

KW - HIV Infections

KW - Humans

KW - Interleukin-6

KW - Kaplan-Meier Estimate

KW - Male

KW - Middle Aged

KW - Neoplasms

KW - Predictive Value of Tests

KW - Prospective Studies

KW - Randomized Controlled Trials as Topic

KW - Risk Factors

KW - Tumor Markers, Biological

U2 - 10.1097/QAD.0b013e32835f6b0c

DO - 10.1097/QAD.0b013e32835f6b0c

M3 - Journal article

C2 - 23945504

SN - 1350-2840

VL - 27

SP - 1433

EP - 1441

JO - AIDS, Supplement

JF - AIDS, Supplement

IS - 9

ER -