Prospective evaluation of serum IL-16 and risk of prostate cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Background: Sexually transmitted infections and chronic inflammation have been associated with an increased risk of prostate cancer. Inflammatory mediators, such as cytokines and free radicals, have been hypothesized to play a role.

Methods: To explore the role of inflammation in prostate cancer risk further, we examined the association between pre-diagnostic serum levels of interleukin-16 (IL-16), an important pleiotropic cytokine, and prostate cancer risk among 932 Caucasian cases and 942 controls and 154 African-American cases and 302 controls in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Serum IL-16 was quantified using enzyme-linked immunoassay. Logistic regression was used to estimate associations between IL-16 and prostate cancer risk, separately by race.

Results: Although no association between IL-16 and prostate cancer overall was observed among Caucasians (p = 0.27), a significantly increased risk of high-grade prostate cancer, defined as Gleason ≥ 7 (p_het = 0.02), was observed with increasing levels of IL-16 (OR_{3rd vs. 1st tertile} = 1.37, 95% CI 1.04-1.81, p_trend = 0.02). We also discovered a significant interaction between IL-16 and history of gonorrhea (p = 0.04). Among Caucasian men with a history of gonorrhea, elevated IL-16 levels were associated with an increased risk of prostate cancer (OR_{3rd vs. 1st tertile} = 3.64, 95% CI 1.14-11.6) but no association was seen among those without a history of gonorrhea (OR_{3rd vs. 1st tertile} = 1.06, 95% CI 0.83-1.34). No associations were observed among African-Americans.

Conclusions: This study found evidence that higher pre-diagnostic IL-16 levels may be associated with increased risk of high-grade disease, supporting inflammation as potential mechanism by which sexually transmitted diseases may increase risk.