Coffee, PI3K signaling pathway, and prostate cancer: a prospective study in the Health Professionals Follow-up Study

Abstract

Higher coffee intake has been associated with reduced risk of prostate cancer, particularly aggressive forms. The activation of the PI3K signaling pathway plays an important role in prostate carcinogenesis. To evaluate associations between pre-diagnostic coffee intake and a PI3K activation score, the expression/presence of PI3K regulators, and downstream effectors in tumor tissue from men with prostate cancer in the Health Professionals Follow-up Study, a prospective cohort study conducted in the US. A case-only study design was applied. Coffee intake was assessed using validated food frequency questionnaires completed in 1986 and every four years thereafter until prostate cancer diagnosis. Study participants comprised 1,242 men diagnosed with prostate cancer from 1986 to 2009 and with tumor markers assessed from tissue microarrays constructed from tumor specimens. The outcomes include the PI3K activation score; expression of insulin receptor and IGF1 receptor; angiogenesis markers; and presence of the tumor suppressor PTEN, chronic and acute inflammation, simple atrophy, and post-atrophic hyperplasia. Multivariable linear or logistic regression was conducted to estimate associations between coffee intake and tumor marker expression/presence. Among coffee drinkers (86.6% of the population), median (25th-75th) coffee intake was 2 (1-3) cups/day. The associations between coffee consumption and the tumor markers of interest were generally weak with modest precision. When comparing men who drank >3 cups/day of coffee with nondrinkers, the absolute percent difference in the PI3K activation score and angiogenesis markers ranged from 0.6% to 3.6%. The odds ratios for PTEN loss, IGF1 receptor and insulin receptor expression, and presence of chronic and acute inflammation, simple atrophy, and post-atrophic hyperplasia also were not statistically significant, were imprecise, and ranged from 0.82 to 1.58. Coffee intake was not observed to be associated with PI3K activation, related regulators, and several effectors in prostate tumor tissue. Studies exploring alternative pathways or earlier steps in carcinogenesis are needed to investigate the underlying mechanisms of the coffee and prostate cancer association.