Study illustrates how genetic and environmental disruptions of the circadian clock can drive colorectal cancer progression

In a new study led by the University of California at Irvine, researchers define how the circadian clock affects cell growth, metabolism and tumor development. Their research also reveals how disruption of the circadian clock affects genome stability and mutations that may further stimulate critical tumor-promoting pathways in the gut.

The study, titled “Disruption of circadian clock leads to loss of Apc from heterozygosity to accelerate colorectal cancers,” was published today in Science Developments.

In this study, researchers found that both genetic disruption and environmental disruption of the circadian clock contribute to the tumor suppressor mutation of adenomatous polyposis of the coli (APC), which is found in the vast majority of human colorectal cancers (CRC). APC point mutations, deletions, and loss of heterozygosity (LOH) events have been reported in approximately 80% of human CRC cases, and it is these mutations that result in the initiation of intestinal adenoma development.

“As a society, we are exposed to several environmental factors that influence our biological clock, including night work, ‘prolonged light exposure, changes in sleep/wake cycles, and altered eating behavior,’ said Selma Masri, PhD, assistant professor of biological chemistry. at the UCI School of Medicine. “Strikingly, we have seen an alarming increase in several early-onset cancers, including most colorectal cancers. The underlying trigger for this increased incidence of most cancers in adults in their 20s and 30s remains undefined. However, based on our findings, we now believe that disruption of the circadian clock plays a crucial role.”

According to the National Institutes of Overall health, there is had an alarming increase in early colorectal cancers in young people. Today, nearly 10% of CRC cases are diagnosed in people under the age of 50 years, and this trend is constantly increasing. Suspected risk factors include environmental aspects, such as lifestyle and dietary factors, which are known to affect the circadian clock.

Mutations APCs are also associated with second knocks in major oncogenic pathways including Kras, Braf, p53 and Smad4, and these mutations drive progression to adenocarcinoma, collectively contributing to the development of the disease. Our findings now implicate disruption of the circadian clock in driving additional genomic mutations that are essential for accelerating colorectal cancer.

The circadian clock is an internal biological stimulator that governs many physiological processes. Research at the Masri Lab primarily focuses on how disruption of the circadian clock is involved in the development and progression of certain types of cancer. Masri lab researchers are actively pursuing further research aimed at defining the impact of the circadian clock on other types of cancer.80

Financial support for this study was provided by the Countrywide Institutes of Wellness/Countrywide Cancer Institute, Issue Foundation, V Basis for Cancer Research, Treatment Study Coordinating Committee, Johnson and Johnson and the UCI Chao Family Detailed Cancer Center’s Anti-Cancer Center. Challenge.

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