Predicting the risk of diabetes and deadly cancers -

What role does prostasin play in cancer and diabetes?

When people have high levels of a specific protein, it's associated with a higher risk of developing diabetes. Those affected also have an increased risk of dying from cancer.

This has become clear in a new study involving experts from Sweden's Lund University, which looked at the link between plasma prostasin, diabetes and cancer mortality risk. The results of the study have been published in the specialized journal "Diabetologia".

Blood samples from over 4,000 people evaluated

To investigate the link between prostasin blood levels and cancer mortality in the general population, the team analyzed blood samples from more than 4,000 middle-aged Swedish adult participants.

The blood samples were taken over a decade ago as part of the ongoing Malmö Diet and Cancer Study. Of the participants, 361 (eight percent) already had diabetes at the start of the study.

After eliminating potential confounders, the team found that elevated prostasin levels were positively associated with the presence of diabetes. The researchers report that the likelihood of existing diabetes in people in the highest prostasin quartile was almost twice as high as in the lowest prostasin quartile.

702 participants developed diabetes

Next, the researchers analyzed clinical data from the same cohort (excluding 361 people with existing diabetes) through the end of 2019. They wanted to determine links to new cases of diabetes.

During a median follow-up of 22 years, 702 participants developed diabetes. Longitudinal analyzes revealed a linear relationship between prostasin and new-onset diabetes.

Higher risk of diabetes with high prostasin levels

It was found that participants with prostasin in the highest quartile had a 76% higher risk of developing diabetes than participants in the lowest prostasin quartile.

Interestingly, prostasin levels were found to be a more accurate predictor of diabetes in younger participants and people with lower blood sugar and better kidney function, the researchers explain.

Experts believe that high levels of prostasin may be a compensatory response to high blood sugar (hyperglycemia), but may not be enough to stop or reverse deterioration in blood sugar control.

Prostasin is excreted in the urine, so normal kidney function can help maintain optimal prostasin blood levels, the scientists say.

Association of prostasin with cancer mortality

In further analysis, the team found that there is a significant association between prostasin and cancer mortality and all-cause mortality. During the average follow-up period of 24 years, 651 participants died of cancer.

According to experts, participants with blood levels of prostasin in the highest quartile were 42% more likely to die of cancer than those in the lowest quartile.

For each doubling of prostasin concentration, the risk of death from cancer increased by 139% and by 24% in participants with and without high blood sugar (impaired fasting blood sugar). According to the researchers, however, no link was found for cardiovascular mortality.

Diabetes risk markers and cancer death risk

“Prostasin is a potential new risk marker for the development of diabetes and for cancer mortality, especially in people with high blood sugar. It is easily measurable, which increases its potential as a future warning marker," said study author Dr. Xue Bao from the Affiliated Hospital of the University of Nanjing in China.

"This is the most comprehensive analysis of its kind to date and sheds new light on the biological link between diabetes and cancer," adds study author Professor Gunnar Engström of the University of Lund in a press release.

How is prostasin related to tumors?

According to experts, prostasin plays a role in regulating several biological signaling pathways associated with diabetes, which are also implicated in the development and promotion of certain types of cancer.

Prostasin is a stimulator of epithelial sodium channels, which regulate sodium balance, blood volume and blood pressure. The epithelial sodium channel is involved in tumor suppression, glucose metabolism, and hyperglycemia-associated tumor pathology, the researchers explain.

Prostasin could offer cancer treatment approaches

Prostasin could mediate the process from high blood sugar to cancer, or at least serve as a marker of cancer susceptibility in people with high blood sugar, but more studies are needed to determine this.

"Prostasin may only be an indicator of disease onset, but it could also be causally relevant, which is exciting as it opens up the possibility of targeting this protein with future diabetes treatments. and cancer," says Professor Engström.

Diabetes increases the risk of cancer

According to the team, previous studies have already provided evidence that diabetes is associated with an increased risk of developing various types of cancers and fatal cancers.

Another study showed that people with type 2 diabetes are about twice as likely to develop pancreatic, endometrial and liver cancer. In addition, the risk of colon cancer increased by 30% and that of breast cancer by 20%. (as)

Author and source information

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This text corresponds to the specifications of the specialized medical literature, medical guidelines and current studies and has been verified by health professionals.

Sources:

Xue Bao, Biao Xu, Iram Faqir Muhammad, Peter M Nilsson, Jan Nilsson, Gunnar Engström: Plasma prostasin: a new risk marker for diabetes incidence and cancer mortality; In: Diabetologia (published 08/04/2022), DiabetologiaDiabetologia: protein that can predict future risk of diabetes and identified cancer death (published 08/04/2022), DiabetologiaEdward Giovannucci, David M. Harlan, Michael C. Archer, Richard M. Bergenstal, Susan M. Gapstur, et al.; : Diabetes and Cancer: A Consensus Report; in: Diabetes Care (published 01/07/2019), Diabetes CareKonstantinos K Tsilidis, John C Kasimis, David S Lopez, Evangelia E Ntzani, John PA Ioannidis: type 2 diabetes and cancer: an umbrella review of meta-analyses of observational studies; in: BMJ (published on 02.02.2015), BMJ

Important note:
This article contains general advice only and should not be used for self-diagnosis or treatment. It cannot substitute a visit to the doctor.