New research explores how genetic and environmental disruption of the circadian clock can impact colorectal cancer (CRC) progression.
According to the National Institutes of Health, there has been an alarming rise in early-onset colorectal cancer among young individuals. Today, nearly 10 percent of CRC cases are now diagnosed in people younger than 50 years, and this trend is on a steady rise. Suspected risk factors include environmental aspects, such as lifestyle and dietary factors, which are known to affect the circadian clock.
The study, published in the journal Science Advances, was led by researchers at the University of California, Irvine and focused on defining how the circadian clock influences cell growth, metabolism, and tumour progression. In addition, the study also discussed how disruption of the circadian clock influences genome stability and mutations that can drive tumour development in the intestine.
According to the study, suspected increased risk of young onset CRC include environmental aspects such as lifestyle and dietary factors, which are known to affect the circadian clock. The authors found that both genetic and environmental disruption of the circadian clock accelerate the adenomatous polyposis coli or Apc-driven CRC pathogenesis in vivo.
Authors sought to evaluate the molecular mechanism of how the circadian clock disruption accelerates CRC.
To address this, the researchers developed a new tissue-specific genetically engineered mouse model (GEMM) to define the molecular pathways linking to circadian disruption and pathogenesis of CRC. According to the authors, their findings demonstrate that genetic deletion of both intestinal Apc and Bmal1 results in a statistically significant increase in polyp formation versus disruption of Apc alone. In addition, the results suggested that environmental disruption of the circadian clock accelerated tumour burden in our Apc mutant GEMM.
“As a society, we are exposed to several environmental factors that influence our biological clock, including night shift work, extended light exposure, changes in sleep/wake cycles and altered feeding behaviour,” said Selma Masri, PhD, assistant professor of biological chemistry at UCI School of Medicine in a statement. “Strikingly, we have seen an alarming increase in several young-onset cancers, including colorectal cancer. The underlying cause of this increased incidence of cancer in adults in their 20s and 30s remains undefined. However, based on our findings, we now believe that disruption of the circadian clock plays an important role.”
References
Seldin MM, Waterman ML, Masri S. Disruption of the circadian clock drives Apc loss of heterozygosity to accelerate colorectal cancer. Sci Adv. 2022 Aug 12;8(32):eabo2389. doi: 10.1126/sciadv.abo2389. Epub 2022 Aug 10. PMID: 35947664.