Liver cancers are commonly thought to be driven by heavy alcohol use or chronic hepatitis B or C virus infection.
But a new grant awarded to Fred Hutch Cancer Center epidemiologist Trang VoPham, PhD, MPH, MS, will investigate whether the most common form of liver cancer ― hepatocellular carcinoma, or HCC ― is also driven by something completely unrelated to alcohol use or viral infection: a disruption in circadian rhythms.
VoPham was recently awarded a Research Scholar Grant of nearly $1 million from the American Cancer Society to lead the first-ever epidemiologic study of solar jet lag exposure and HCC risk in the world.
Joining her as co-investigators are George N. Ioannou MD, MS (University of Washington and Veterans Affairs Puget Sound Health Care System), Kristin Berry (Wyatt), PhD (Veterans Affairs Puget Sound Health Care System), Nicole J. Kim, MD, MPH (University of Washington), Philip Vutien, MD, MS (University of Washington), Matthew D. Weaver, PhD (Harvard Medical School), and Jason “Jay” Mendoza, MD, MPH (Fred Hutch).
A leading cause of death globally and here in the United States, HCC’s five-year relative survival rate is 22%, per the National Cancer Institute.
“The five-year survival rate is even lower at 13% when liver cancer is diagnosed at a regional stage,” VoPham said. “And when it metastasizes ― progresses to a distant stage ― it’s only 3%. It’s critical to identify novel, modifiable risk factors to reduce the risk of developing this cancer and emerging evidence suggests that solar jet lag exposure may be one such HCC risk factor.”
What on earth is solar jet lag?
VoPham defines it as a specific type of circadian disruption (i.e., circadian misalignment) caused by differences in the timing of a person’s exposure to light. In short, it’s when your internal clock, or circadian rhythm, is misaligned with the sun’s clock. Solar jet lag was a term coined by chronobiologists.
“The later exposure to sunrise and sunset that is experienced by those with a western time zone position tends to set their own internal clock to a later hour. This results in delayed circadian phase, suppression of melatonin, and reduced sleep propensity, which reduces sleep duration and sleep quality because of fixed early awakenings for work or social commitments,” VoPham said. “That creates a chronic source of circadian disruption similar to what might be experienced with chronic exposure to jet lag ― thus the term solar jet lag.”
Just as traveling from time zone to time zone can cause sleep disturbances, fuzzy thinking and overall discombobulation, VoPham said solar jet lag can also result in negative health effects including, potentially, an increased risk for liver cancer.
“The circadian clock plays a central role in the regulation of liver function and approximately 10% of the liver transcriptome is rhythmically expressed, including genes involved in metabolism,” she wrote in her grant proposal. “Circadian disruption, such as from shift work, has been implicated in liver cancer, but another source of circadian disruption is solar jet lag, which occurs from geographic variation in timing of environmental light exposure due to time zone position.”
This chronic mismatch between the sun clock and the social clock leads to solar jet lag, which may impact liver cancer through mechanisms that promote obesity, diabetes and metabolic dysfunction-associated steatotic liver disease, or MASLD (formerly known as non-alcoholic fatty liver disease), via dysregulation of glucose metabolism and bile acid synthesis.
Currently, the major known risk factors for HCC include cirrhosis (chronic liver disease), chronic hepatitis B virus, chronic hepatitis C virus, heavy alcohol consumption, MASLD, obesity and diabetes. MASLD is currently the fastest growing known cause of HCC.
American Society of Preventive Oncology Annual Meeting
50 Years of Impact: Empowering Communities Through Cancer Prevention Research
April 12-14, 2026 in Denver
Fred Hutch research assistant Malia Cortez, MS, will present an oral talk on “A New Scalable Tool to Visualize Neighborhood-Level Health and Environmental Exposures for Cancer Center Catchment Area Analytics” from 1-2 p.m. on Monday, April 13.
VoPham, who joined Fred Hutch in 2019 and is an associate professor in the Public Health Sciences Division, runs the Geospatial Exposome Lab, or geoexlab, which focuses on research (and interventions) at the intersection of geospatial science, epidemiology and the environment.
In addition to researching unexpected cancer drivers, her lab develops digital tools such as a new geospatial web app that will allow people to learn about neighborhood-level health and environmental data (think wildfire smoke, radon or high temperatures). All aspects of this new web app are being created using open-source software and data, which will facilitate scaling this technology to serve communities of cancer center catchment areas across the United States.
VoPham has also published a number of studies examining the associations between air pollution, wildfires and chronic disease outcomes (e.g., survival after cancer diagnosis).
In previously published work leveraging cancer registries, VoPham and co-investigator Weaver showed that “circadian misalignment from residing in the western region of a time zone may impact hepatocarcinogenesis,” or the development of liver cancer. This preliminary work also showed the association between solar jet lag and HCC risk was stronger among Asian, Pacific Islander and Alaska Native/American Indian people compared to non-Hispanic White individuals.
VoPham said there are marked disparities in HCC, with higher risk among men than women and among Alaska Native/American Indian and Hispanic people than other racial or ethnic groups.
So far, these disparities are not well understood.
“Differences in access to healthcare and/or prevalence of HCC risk factors explains some, but not all, of the observed disparities,” she said. “Alaska Native, American Indian, and Hispanic people are disproportionately impacted by this disease.”
VoPham believes solar jet lag may play a role.
In 2024, VoPham and her co-investigator Weaver published work on a newly developed (and validated) geospatial light exposure model that calculates solar jet lag scores. Higher scores indicate a higher “environmental circadian misalignment” or higher likelihood of exposure to solar jet lag.
This new geospatial model is currently being used to investigate the association between solar jet lag and sleep health in a recently funded National Institutes of Health R21 grant co-led by VoPham and Weaver.
Now, they’ll pair their improved high-resolution geospatial light exposure model for solar jet lag with electronic health records from the Veterans Health Administration, the largest integrated health care system in the United States.
“We will examine 23 million VA patients, of which there are 60,000-plus HCC cases diagnosed from 2001 to 2024,” VoPham explained.
Scaling this new geospatial light exposure model for large-scale epidemiologic analyses is possible through leveraging computational and data science resources in the Fred Hutch Office of the Chief Data Officer WILDS (Workflows Integrating Large Data and Software).
The team will ascertain HCC outcomes as well as glean data regarding race and ethnicity; health conditions like obesity, diabetes and MASLD; socioeconomic status; medications; laboratory/diagnostic tests (to determine hepatitis infection); and lifestyle behaviors such as smoking.
Solar jet lag exposure, she said, will be estimated by using a geographic information system, or GIS, that links patient geocoded residential address histories ― over time ― with their new high-resolution geospatial light exposure model.
The team’s number one aim is to quantify the association between solar jet lag exposure and HCC risk; in other words, to show through data that higher solar jet lag exposure is associated with a higher risk of developing HCC.
They also want to better understand the disparities that exist in the disease.
“We hypothesize that higher solar jet lag exposure will be more strongly associated with HCC risk among Alaska Native/American Indian and Hispanic people due to their residence in high-solar jet lag areas like Alaska and South-Central U.S.,” VoPham said. “We also believe that the higher incidence in men may in part be due to certain differences such as in time spent outdoors.”
Since solar jet lag is a modifiable exposure, that is, people can take steps to counteract its affect, the team eventually plans to create interventions to help those who may be impacted.
Personal-level interventions could include exposure to light at appropriate times of day to reduce solar jet lag and promote circadian alignment; promoting sleep and circadian health through behavioral and environmental modifications such as limiting exposure to light at night (e.g., window shades, eye masks); optimizing sleep timing, duration, and regularity; and limiting the use of devices that emit blue-enriched light at night.
Findings could also lead to policy-level interventions to reduce circadian disruption, such as flexible or hybrid work hours and delayed school start times.
The American Cancer Society’s mission is to improve the lives of people with cancer and their families through advocacy, research and patient support, to ensure everyone has an opportunity to prevent, detect, treat and survive cancer.
Funding for the geospatial light exposure model came from the NIH/NIEHS P30ES007033 University of Washington Interdisciplinary Center for Exposures, Diseases, Genomics and Environment and the Fred Hutch Public Health Sciences Division.
Computational and data science resources came from the Fred Hutch Office of the Chief Data Officer WILDS (Workflows Integrating Large Data and Software, Firman, Bishop, et al. 2026. WILDS WDL Library [Version 0.1.0] [Computer software] https://github.com/getwilds/wilds-wdl-library).
Funding for this new study comes from the American Cancer Society Research Scholar Grant RSG-25-1516665-01-ESED.
Diane Mapes is a senior editor and writer at Fred Hutch Cancer Center, who's written for NBC News, TODAY, CNN, MSN, Seattle Magazine and other publications. A breast cancer survivor and patient advocate, you can reach her at dmapes@fredhutch.org or doublewhammied.com / @double_whammied / @doublewhammied.bsky.social. Just diagnosed and need information and resources? Visit our Patient Care page.
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