Beyond inhibition of cholesterol biosynthesis, statins appear to have pleiotropic effects, including modulation of cell growth, apoptosis, and inflammation. Statins may also reduce cancer risk, particularly among HIV-infected (HIV+) subjects who experience chronic inflammation and immune activation. Small observational studies have suggested an association between statin use and lower cancer risk in HIV+ but small sample sizes limited cancer type-specific analyses. Comparison of the association of statin exposure with cancer in HIV+ and HIV-uninfected comparators (HIV-) is also lacking. We used the Veterans Aging Cohort Study (VACS), a large observational cohort with cancer registry linkage and detailed pharmacy data to address these questions
We followed statin users identified between 2000-2012, beginning 180 days after an index date defined as first statin prescription for users and a random visit date in the same year for non-users. To account for known and potential confounders we fit a propensity score (PS) model for statin use including age, calendar year, smoking, chronic diseases (e.g., diabetes, hypertension, HCV co-infection, alcohol use disorder), and laboratory values (e.g., LDL, albumin). We matched each statin user to up to four non-users by PS. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CI) associated with statin use for all cancers, individual cancers, infection-related cancers (anal, colorectal, head and neck, liver, lymphoma, and stomach) and notinfection-related cancers.
The PS-matched sample included 48,214 participants, of whom 23,512 (48.8%) were incident statin users. Incident cancers were diagnosed in 940 (9.7%) of 9,649 HIV+ and 3,079 (8.0%) in 38,565 uninfected. Overall, statin use was associated with ~20% reduced risk of any cancer [HR 0.82 (95% CI 0.77 – 0.88)] and ~40% lower risk for infection-related cancers [HR 0.62 (95% CI 0.55 – 0.70)]. In general, the association was stronger in HIV+, but the interaction did not reach statistical significance except for non-Hodgkin lymphoma
Statin exposure is associated with lower risk of cancer independent of HIV status. This protective effect appears to be stronger for infection-related cancers.