While biomarkers may be used to diagnose disease, the ups and downs of biological molecules may not depend entirely on whether a particular disease is present. Protein levels in the blood stream, for example, may vary with individual genetic, clinical, and lifestyle factors.
This observation isn’t exactly novel. Biomarkers for specific diseases have been linked with lifestyle and demographic factors. For example, in a study of diabetes that considered how well the disease could be predicted by assessing levels of a protein called sex hormone binding globulin (SHBG), relevant factors were found to include age, reproductive history, usage of exogenous estrogen, body mass index, physical activity, alcohol consumption, coffee intake, smoking, and various dietary factors.
When these findings appeared last year, study leader Simin Liu, M.D., a professor of epidemiology and medicine at Brown University, said, “This protein seems to capture the cumulative effect between the gene and our environment in reflecting a metabolic state of our body, particularly in the liver, ultimately affecting diabetes risk.”
If individual genetic and lifestyle factors can influence one biomarker, they can presumably influence many other biomarkers. Yet biomarkers used for diagnosing disease should preferably indicate variations in protein levels only for those individuals who are suffering from a particular disease. Nor should they vary for reasons that have nothing to do with the disease.
To address this issue in a systematic way, researchers from Uppsala University recently conducted a large-scale study of non-disease-related factors that can influence protein levels in the bloodstream. Specifically, the researchers, led by Stefan Enroth, Ph.D., analyzed 92 protein biomarkers for cancer and inflammation in a clinical study of 1,000 healthy individuals.
The results of the study appeared August 22 in Nature Communications, in an article entitled, “Strong effects of genetic and lifestyle factors on biomarker variation and use of personalized cutoffs.” According to this article, hereditary factors play a significant role for more than 75% of the proteins, and a detailed genetic analysis demonstrates 16 genes with a strong effect on protein levels.
“These results are important, as they show which variables are significant for variations in the measurable values,” explained Dr. Enroth. “If these factors are known, we have a greater possibility of seeing variations and we get clearer breakpoints between elevated values and normal values. By extension this may lead to the possibility of using more biomarkers clinically.”
According to the study, genetics and lifestyle together account in some cases for more than 50% of variations in protein levels among healthy individuals. This means that information about both genetic and lifestyle factors must be taken into account in order for protein biomarkers to be used effectively.