In a study she conducted while she was a CU Boulder postdoctoral researcher, Elizabeth Holzhausen and colleagues find a link between night-shift work and prostate-cancer risk

More workers than ever before can take advantage of flexible schedules. But some in health care, emergency services, manufacturing and other occupations are often constrained to regular overnight shifts. Epidemiologist Elizabeth Holzhausen had questions about the serious health risks associated with night shift work, specifically regarding prostate cancer.

Holzhausen, who worked as a postdoctoral associate in the University of Colorado Boulder Department of Integrative Physiology before recently becoming an assistant research professor at the Johns Hopkins Bloomberg School of Public Health, is coauthor—along with Jinyoung Moon of the College of Natural Sciences, Seoul National University, and Yongseok Mun of the Hallym University Kangnam Sacred Heart Hospital in Seoul—of in men who regularly work the night shift.

They also examined whether the number of years on that shift increased the risk to employees. Their paper was recently published in the journal Heliyon.

For the study, Holzhausen and her colleagues conducted a meta-analysis, examining a large number of studies that looked at prostate cancer incidence and its possible relationship to night-shift work. One motivation for the meta-analysis was that there had been mixed results regarding any correlation between prostate cancer and night-shift workers in past studies. Holzhausen and the research team hoped to settle the matter with a rigorous meta-analysis.

Previous research has shown that working the night shift can present numerous health hazards. Along with heightened cancer risk, night shifts can increase the probability of heart disease, stroke, type 2 diabetes and sleep disorders in workers.

According to the Centers for Disease Control, 13% of men will get prostate cancer, and approximately 3% of men die from the disease, which is more likely to strike older men. Definitive current figures are difficult to find, but the U.S. Bureau of Labor Statistics reported that in 2018, close to 4% of employees worked the night shift, including approximately 2.5 million men.

Prostate cancer and the night shift

In their study, Holzhausen and her co-authors found that there was a link between increased incidence of prostate cancer and night-shift work. They also determined that the longer men worked the night shift, the higher the risk became. The study showed that workers on the night shift for just one year had a 1% increase in prostate cancer risk, but for workers who had 30 years of overnight shifts, that risk jumped to 39%.

“I was surprised about the magnitude of the findings,” says Holzhausen. “There are a lot of people who work the night shift, so this is especially impacting people who work this shift over a long period of time.”

As Holzhausen explains, the disruptions to the body from shift work are significant: “There are several cancers that have been associated with night-shift work, and one of the big things is that we know lack of sleep and circadian misalignment can reduce the functioning of the immune system,” she says. “As a result, [the body’s] surveillance for cancer cells could be impacted if someone is doing chronic night-shift work.”

One of the challenges of the study was controlling for outside factors across a number of different studies that used different methods. A large chunk of the paper describes how the researchers achieved that.

"There are several cancers that have been associated with night-shift work, and one of the big things is that we know lack of sleep and circadian misalignment can reduce the functioning of the immune system."

“We were very rigorous about what studies we included," says Holzhausen. "Studies where the exposure was maybe nursing or some occupation that could be night-shift work, but they didn't explicitly identify if they were doing night-shift work, were excluded. We only looked at studies where specifically night-shift work was the exposure.”

The researchers also included studies that controlled for socioeconomic status to remove it as a variable in the study. "Nearly all of the studies included in our meta-analysis considered socioeconomic status. We did not analyze socioeconomic status explicitly and aren’t able to make inferences about different socioeconomic strata," says Holzhausen.

"However, the aim in adjusting for socioeconomic status is to estimate the impact of night-shift work on risk of prostate cancer independent of socioeconomic status. In other words, the results we observed are unlikely to be due to differences in socioeconomic status between day- and night-shift workers."

Holzhausen says that since night-shift work is probably not going away anytime soon, night-shift workers should be proactive in mitigating the potential risks: “Get additional screenings for prostate cancer, and take other measures that we know can help prevent prostate cancer, like eating a healthy diet, maintaining a healthy weight, limiting alcohol and not smoking.”

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Tin Tin Su of CU Boulder and Antonio Jimeno of the CU School of Medicine say acceleration-initiative funds will help speed a promising, developed-in-Colorado cancer therapy to patients

After working eight years on a new way to attack some cancers, a pair of  researchers are closer to their goal of bringing their therapy to patients—as one of nine research endeavors receiving funding from the  (AAI).

The project is led jointly by Tin Tin Su, co-leader of the cancer center’s  and professor of molecular, cellular and developmental biology at the University of Colorado Boulder, and , a co-leader of the CU Cancer Center’s  and professor in the 's .

Tin Tin Su, a CU Boulder professor of molecular, cellular and developmental biology, discovered that a molecule found in the firecracker bush can be synthesized to target cancer stem cells. 

Jimeno says it’s significant that the AAI award is for a potential cancer therapy “that was discovered in Colorado and will use Colorado funds from a Colorado donor to help Colorado cancer patients.”

He adds: “Here at the CU Cancer Center, we can get things done really well and really quickly, provided we have the focus and the resources. And this grant provides both.”

Their work involves the use of a synthetic small molecule called SVC112, which has been shown to effectively target cancer stem cells in , the main focus of Jimeno’s .

Cancer stem cells produce cells that make up most of a tumor’s bulk. They often are resistant to traditional therapies such as radiation and chemotherapy and can recover from treatment to produce more tumor cells. The U.S. Food & Drug Administration has approved the use of protein synthesis inhibitors that slow or stop cancer cell growth, but they can be toxic to healthy cells as well as cancer cells.

SVC112 was originally synthesized by SuviCa, Inc., a Boulder-based biotechnology company co-founded by Su. It’s based on the chemical bouvardin, found in the firecracker bush, Bouvardia ternifolia, a red-flowering plant that grows in the Southwest and Mexico.

The discovery in Su’s research lab at CU Boulder of bouvardin’s remarkable ability to prevent regeneration of tissues in the fruit fly led to the current studies.

Previous research by Jimeno, Su, and others showed that SVC112 can keep cancer stem cells from manufacturing more tumor cells. The pre-clinical research indicated that SVC112 can be more effective than the FDA-approved protein synthesis inhibitor homoharringtonin (HHT), and with less toxicity, while also increasing the effects of radiation treatment.

“It’s effective in ways that other drugs are not,” Su says. “This compound has shown efficacy in squamous head and neck cancer, in salivary gland cancer, colorectal cancer, and leukemia models. This is very exciting, because it proves the biologic point that multiple tumor types rely on the same mechanisms, the same proteins, to become invasive, to grow and to metastasize.”

 

This is very exciting, because it proves the biologic point that multiple tumor types rely on the same mechanisms, the same proteins, to become invasive, to grow and to metastasize.”

 

Su points out that SVC112 passed three reviews to be approved to receive milestone-based support from the National Cancer Institute’s (NCI)  in 2023, providing resources for SVC112’s development. NCI is part of the National Institutes of Health.

Jimeno says that the five-year AAI grant will help fund the arduous next steps in developing SVC112. First, the researchers will conduct pre-clinical experiments leading to an investigational new drug filing to the FDA within two years. Next, he says, plans call for a first-in-human Phase 1a  in cancer patients “to determine the safe, optimal way of delivering this to humans, employing all the clinical-trials capabilities of our university, including the ,” followed by a Phase 1b trial.

Cancers to be targeted in later stages of the clinical trials may change based on early results, if the researchers see patients with certain cancers responding especially well, Jimeno says.

The AAI recipients were announced in January by CU School of Medicine Dean John J. Reilly, Jr., MD, during his annual .

 is a writer for the Anschutz School of Medicine, which published a .

Top image: Bouvardia ternifolia, or firecracker bush (Photo: U.S. Forest Service)

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