In his doctoral dissertation completed at the University of Jyväskylä, Finland, Tero Sievänen demonstrates that the cancer risk of Lynch syndrome carriers can be assessed based on circulating microRNA profiles. This helps in developing current screening methods and targeting screenings for high-risk individuals. Additionally, the study corroborates previous findings by demonstrating that a healthy lifestyle can mitigate cancer risk in Lynch syndrome carriers. Lifestyle factors, such as weight gain, and their association with cancer development were found to be particularly pronounced in men.
Lynch syndrome is a hereditary cancer syndrome that predisposes its carriers to various cancers, especially colorectal cancers. Due to the hereditary cancer risk, Lynch syndrome carriers undergo cancer screenings throughout their lives. However, current research indicates the need to improve the current screening methods to better account for individual cancer risk and more effectively target high-risk carriers.
It has been shown that circulating microRNA profiles can be used in predicting non-hereditary colorectal cancer development. MicroRNAs are small molecules that regulate gene expression in their target tissues, in response to factors such as diseases and physical activity. Circulating microRNAs are also an important part of intercellular communication, which is why their levels can reflect changes occurring in tissues.
"The aim of this study was to assess whether circulating microRNA profiles can be used to predict cancer development in Lynch syndrome carriers during a four-year follow-up period," says Sievänen.
"Additionally, the study investigated the potential association between circulating microRNA profiles and lifestyle factors related to cancer risk, such as high body mass index and low physical activity."
The study observed that that the circulating microRNA profiles of cancer-free Lynch syndrome carriers differed significantly from healthy controls but were similar to those of patients with non-hereditary colorectal cancer. Additionally, circulating microRNAs predicted colorectal cancer development during the prospective surveillance period.
"These results align with previous research findings in that changes in microRNA profiles predict the development of colorectal cancer," Sievänen notes.
"In Lynch syndrome, colorectal cancer can develop much more rapidly than in those without a hereditary predisposition to the disease. When cancer is detected early, it is easier to treat."
Physical activity and weight maintenance might reduce Lynch syndrome cancer risk
Previous studies suggest that Lynch syndrome cancer risk can be reduced through a healthy lifestyle. Thus, the thesis also examined how changes in adulthood body weight and physical activity impact overall cancer risk and colorectal cancer risk. It was observed that weight gain was associated with a higher cancer risk in adulthood only in men but not in women. Additionally, it was found that men who participated in guided leisure-time physical activity were less likely to develop cancer.
"Lifestyle factors and their association with cancer development differ between men and women," Sievänen explains.
"This may be due to physiological differences, such as variations and changes in body composition over the life course. Adhering to healthy lifestyle is important also for Lynch syndrome carriers."
Tero Sievänen will defend his doctoral dissertation in gerontology and public health, "The associations of circulating microRNAs and lifestyle habits with cancer risk in Lynch syndrome", on September 20, 2024, at 12 noon in the C4 Hall of the Capitolium Building at the University of Jyväskylä. His opponent is Professor Arto Mannermaa (University of Eastern Finland) and the custos is Associate Professor Eija Laakkonen (University of Jyväskylä). The public defense will be held in Finnish.
Tero Sievänen graduated from Nastopoli General Upper Secondary School, Nastola, Finland, in 2009 and earned a Master of Science degree from the University of Jyväskylä in 2019. Since 2017, he has worked as a research assistant, then as a grant researcher, and finally as a doctoral researcher at the Faculty of Sport and Health Sciences at the University of Jyväskylä. He is currently working as a project researcher at the Bioinformatics Center of University of Eastern Finland.
