Decreased macrophage inflammatory protein (MIP)-1α and MIP-1β increase the risk of developing nasopharyngeal carcinoma

Background: The association of circulating inflammation markers with nasopharyngeal carcinoma (NPC) is still largely unclear. This study aimed to comprehensively explore the relationship between circulating cytokine levels and the subsequent risk of NPC with a two-stage epidemiologic study in southern China. Methods: The serum levels of 33 inflammatory cytokines were first measured in a hospital-based case-control study (150 NPC patients and 150 controls) using multiplex assay platforms. Marker levels were categorized into two or more groups based on the proportion of sample measurements that was above the lower limit of detection. Odds ratios (ORs) and 95% confidence intervals (CIs) relating the serum marker concentration to the risk of NPC were computed by multivariable logistic regression models. The associations were validated in 60 patients with NPC and 120 controls in a subsequent nested case-control study within a NPC screening trial. Potential interactions between serum cytokines and Epstein-Barr virus (EBV) relating to the risk of NPC were assessed using a likelihood ratio test. Results: The levels of serum macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta in the highest categories were associated with a decreased risk of NPC in both the case-control study (MIP-1 alpha: OR = 0.49, 95% CI = 0.26-0.95; MIP-1 beta: OR = 0.47, 95% CI = 0.22-1.00) and the nested case-control study (MIP-1 alpha: OR = 0.13, 95% CI = 0.03-0.62; MIP-1 beta: OR = 0.20, 95% CI = 0.04-0.94), compared with those in the lowest categories. Furthermore, individuals with lower levels of these two cytokine markers who were EBV seropositive presented with a largely higher risk of NPC compared with patients with higher levels who were EBV seronegative in both the case-control study (MIP-1 alpha: OR = 16.28, 95% CI = 7.11-37.23; MIP-1 beta: OR = 12.86, 95% CI = 5.9-28.05) and the nested case-control study (MIP-1 alpha: OR = 86.12, 95% CI = 10.58-701.03; MIP-1 beta: OR = 115.44, 95% CI = 13.92-957.73). Conclusions: Decreased preclinical MIP-1 alpha and MIP-1 beta levels might be associated with a subsequently increased risk of NPC. More mechanistic studies are required to fully understand this finding.