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Blood Protein Could Signal Increased Risk of Diabetes, Future Cancer Mortality

An analysis of more than 20 years of follow-up data from more than 4000 patients in the Malmö Diet and Cancer Study shed light on associations between prostasin concentrations and risk of developing diabetes and cancer mortality.

Data from a Swedish study of more than 4000 adults followed for more than 2 decades suggests high concentrations of plasma prostasin was associated with an increased risk of developing diabetes or dying from cancer.

An analysis of data from the ongoing Malmö Diet and Cancer Study, results of the analysis indicate patients the highest quartile of prostasin, a protein found in epithelial cells lining the surfaces and organs of the body, had a 76% greater risk of developing diabetes and a 43% greater risk of cancer-related mortality than those in the lowest quartile of prostasin concentrations in adjusted analyses.

"This is the most comprehensive analysis of its kind to date and sheds new light on the biological connection between diabetes and cancer," said lead investigator Gunnar Engström, MD, PhD, a professor of Cardiovascular Research-Epidemiology at Lund University in Malmö, Sweden, in a statement. "Prostasin may be just an indicator that disease might occur, or could be causally relevant, which is exciting because it raises the possibility of targeting this protein with future treatments for both diabetes and cancer."

Citing an interest in further studying the association between diabetes, cancer, and prostasin, which has been associated with suppression of tumors, glucose metabolism, and hyperglycemia-tumor pathology, Engström and a team of colleagues from Lund University and Nanjing University Medical School sought to examine associations between plasma prostasin and diabetes as well as to explore whether prostasin has influenced risk of cancer mortality risk individuals with hyperglycemia.

To do so, investigators designed their study as an analysis of samples from the Malmö Diet and Cancer Study Cardiovascular Cohort. The first portion of study called for an assessment of the cross-sectional associations between prostasin and diabetes, which included 4658 patients. This cohort had a mean age of 57.5±5.9 years and 39.9% were men. The cohort of patients used in analyses estimating associations of prostasin with incident diabetes and cancer mortality risk excluded 361 patients from the 4658-patient cohort based on prevalent diabetes at baseline.

Investigators pointed out Cox regression analysis was used to assessed associations of prostasin with incident diabetes and cancer mortality risk, with statistical analyses performed with both sex-specific quartiles and per 1 SD. Investigators also pointed out study design called for assessments of the interactions between prostasin and blood glucose levels.

Results of the analysis indicated those in the highest quartile of prostasin concentrations had a nearly doubling in odds of prevalent diabetes compared to those in the lowest quartile (aOR, 1.95 [95% CI, 1.39-2.76]; P <.0001). Overall, 702 patients developed diabetes during a mean follow-up of 21.9±7/0 years and 651 patients died from cancer during a mean follow-up of 23.5±6.1 years.

When assessing risk of incident diabetes and prostasin concentrations, investigators found an increased risk was observed for those in the highest quartile compared to the lowest (aHR, 1.76 [95% CI, 1.41-2.19]; P <.0001), with a 23% increase in risk observed per 1 SD increase in prostasin (aHR, 1.23 [955 CI, 1.13-1.34]; P <.0001). When assessing risk of cancer mortality and prostatic concentrations, investigators found an increased risk was observed for those in the highest quartile compared to the lowest (aHR, 1.43 [95% CI 1.14-1.80]; P=.0008), with a 13% increase in risk observed per 1 SD increase in prostasin (aHR, 1.13 [95% CI 1.04-1.23]; P=.0058).

Investigators highlighted further analysis suggested there was a significant interaction between prostasin and fasting blood glucose for cancer mortality risk (P=.022), with a stronger association observed among those with impaired fasting blood glucose levels at baseline (HR per 1 SD change, 1.52 [95% CI 1.07-2.16]; P=.019).

“Prostasin is a new potential risk marker for the development of diabetes and for cancer mortality, especially in individuals with high blood glucose levels”, said study investigator Xue Bao, of the Affiliated Hospital of Nanjing University Medical School, in a statement. “It is easily accessible, which enhances its potential to serve as a warning marker in the future.”

This study, “Plasma prostasin: a novel risk marker for incidence of diabetes and cancer mortality,” was published in Diabetologia.