A1 Refereed original research article in a scientific journal
Serum TIMP-1 concentrations are associated with cancer incidence and cancer-related mortality in a population-based cohort; 
Authors: Nieminen, Mikko T.; Brandt, Ella; Havulinna, Aki S.; Kamber, Oleg; Tervahartiala, Taina I.; Zeller, Tanja; Blankenberg, Stefan; Salomaa, Veikko; Sorsa, Timo; Pussinen, Pirkko J.; Salminen Aino
Publisher: Springer Science and Business Media LLC
Publication year: 2026
Journal: Scientific Reports
Article number: 23048
Volume: 16
Issue: 1
eISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-026-52354-5
Publication's open availability at the time of reporting: Open Access
Publication channel's open availability : Open Access publication channel
Web address : https://doi.org/10.1038/s41598-026-52354-5
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/527092063
Self-archived copy's licence: CC BY
Self-archived copy's version: Publisher`s PDF
Additional information: The FINRISK data for the present study is available with a written application to the THL Biobank as instructed on the website of the Biobank (https://thl.fi/en/research-and-development/thl-biobank/for-researchers). A sep arate permission is needed from FINDATA (https://www.findata.fi/en/) for use of the electronic health record data.
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.
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Funding information in the publication:
This research was funded by the Research Council of Finland (340750 and 369310 to PJP; 369312 to AS), the Sigrid Juselius foundation (to PJP), the Novo Nordisk foundation (NNF230C0084173 to PJP), and the Paulo foundation (to PJP), the Finnish Dental Foundation (to EB), the Finnish Association of Women Dentists (to EB) and Helsinki University Hospital institutional funding (to MN and TS). Funding for open access publishing was provided by University of Helsinki. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
