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

Abstract

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.

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