Serum TIMP-1 concentrations are associated with cancer incidence and cancer-related mortality in a population-based cohort

Abstract

Abstract The tumor microenvironment is regulated by matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs); however, their utility as cancer biomarkers remains unclear. We investigated the associations of serum MMP-8, TIMP-1, and the MMP-8/TIMP-1 ratio with prevalent and incident cancer in 8448 individuals aged 25–74 years from the FINRISK97 cohort. Participants were followed for incident cancer (n = 1618) for 26 years through the Finnish Cancer Registry. Serum MMP-8 and TIMP-1 concentrations were measured at baseline using immunoassays. Serum TIMP-1 levels were significantly higher in individuals with prevalent and incident cancer, including colorectal and lung cancer, whereas lower MMP-8 levels were observed in colorectal and prostate cancer. Accordingly, the MMP-8/TIMP-1 ratio was reduced in individuals with incident cancer. In age-stratified models adjusted for sex, smoking, and BMI, elevated TIMP-1 levels were strongly associated with incident cancer in participants aged 55–64 years (HR, 95% CI 6.36, 2.50–16.16) and ≥ 65 years (6.23, 1.67–23.21), and with cancer mortality (29.7, 8.25–106 and 18.4, 3.64–93.6). MMP-8 and the MMP-8/TIMP-1 ratio showed weaker associations with incident cancer and cancer mortality only in the 45–54-year age group. These findings support TIMP-1 as a potential biomarker for cancer risk and mortality.