Risk profiling and early detection of colorectal cancer.
Colorectal cancer (CRC), the third most common cancer in men and women in Sweden and, if discovered early, prognosis is good. However, despite considerable therapeutic advances in recent decades, the prognosis for advanced CRC is markedly worse. Effective strategies for the prevention and early detection of CRC therefore have great potential to substantially reduce the overall societal burden of this disease.
Colonoscopy is the gold standard for CRC detection. But does everyone really need this uncomfortable and invasive procedure? What if it was possible to use less invasive methods to identify individuals at high risk of developing CRC, or with asymptomatic premalignant or early malignant lesions? Improving risk profiling to allow selection of individuals with the most to win from preventive strategies and colonoscopy screening is a major challenge in CRC research today and the main purpose of Bethany Van Guelpen's research.
Bethany Van Guelpen's research has an integrative molecular epidemiology approach, using extensive health and lifestyle data and prospectively collected blood samples from the large, population-based cohorts in northern Sweden, archival tumor tissue from CRC cases in the same cohorts, broad OMICS technologies and advanced statistical analyses.
One main research question, funded by the Swedish Cancer Society (Cancerfonden), is the potentially different role of lifestyle-related factors in subtypes of CRC based on particular traits, or combinations of traits, in the tumor. The lifestyle-related factors include: 1. factors involved in one-carbon metabolism, e.g. plasma folate levels, 2. factors involved in energy metabolism, e.g. body constitution and fasting blood glucose levels, and 3. factors involved in inflammation, e.g. diet and inflammatory markers.
A unique set of longitudinally collected blood samples, taken 10 years apart, in approximately 70 CRC cases and 1:1 time-matched control subjects has also been selected from the same cohorts. Epigenomic, targeted proteomic and metabolomic methods are currently being applied to search for biomarkers of CRC or high CRC risk. Results from the discovery phase will then be validated in larger study sets. The CRC subtype and biomarker results will also be compared and integrated, to provide further etiological insights.
Combining blood-based biomarkers with refined risk profiling for personalized CRC prevention and targeted colonoscopy screening has the potential to reduce CRC incidence and mortality.