Background: TH1 cytokines, such as IFNγ and TNFα, and potentially innate cytokines, such as IL6, can potentiate the immune response to tumor. Cytokines, such as IL1β, IL8, and IL10, may suppress anticancer immunity. Thus, we prospectively evaluated the association between peripheral-cytokine concentrations and prostate cancer. Methods: We conducted an age-race matched case-control study (268 pairs) of incident prostate cancer in CLUE-II. We measured plasma IFNγ , IL10, IL12p70, IL1β, IL6, IL8, and TNFα concentrations using an ultrasensitive multiplex kit. ORs and 95% confidence intervals (CI) were calculated using conditional logistic regression. Results: The OR of prostate cancer decreased across quartiles of IFNγ (highest vs. lowest quartiles: OR, 0.49; 95% CI, 0.30-0.81; Ptrend = 0.006), TNFα (OR, 0.56; 95% CI, 0.33-0.96; Ptrend = 0.01), and IL6 (OR, 0.46; 95% CI, 0.26-0.79; Ptrend = 0.007). Higher TNFα (OR, 0.28; 95% CI, 0.09-0.85; Ptrend = 0.01) and IL6 (OR, 0.20; 95% CI, 0.06-0.67; Ptrend = 0.003) concentrations were associated with lower Gleason sum ≥7 disease risk. Other cytokines were not as clearly associated with risk. Conclusions: Men with a prediagnostic circulating TH1 profile and higher IL6 may have a lower risk of prostate cancer, including aggressive disease. Whether this profile reflects (i) an intraprostatic immune environment in benign tissue that protects against prostate cancer, (ii) the immune milieu in response to a prostate adenocarcinoma that inhibits tumor growth and detectability, and/or (iii) a systemic immune profile that mediates the influence of modifiable factors on risk, warrants additional study. Impact: Identifying specific inflammatory cytokines associated with prostate cancer may lead to improved prevention and treatment strategies.
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