Researchers Investigate Molecular Clues in Puzzling Alaska Native Cancer Disparity

Researchers are trying to figure out why Alaska Native people have the highest rates of colorectal cancer incidence in the United States -- and possibly the world. (Photo courtesy: Pexels.com)

SEATTLE—Eric Fox, an Inupiaq Alaska Native, lost his mom to colorectal cancer several years ago. Since then, he has struggled to understand why Alaska Native people have the highest rate of this cancer in the country.

“Between genetics and environment, there has to be some answers,” he said. “This is a call to action.”

Researchers are working to answer this call. Seattle-based Fred Hutchinson Cancer Research Center scientists are teaming with the Alaska Native Tribal Health Consortium to investigate this perplexing health disparity. The three-year project, which began in September 2020, will explore the genetics and microbiome, or communities of microorganisms, of Alaska Natives’ colorectal tumor cells. Better understanding of these factors could lead to targeted drug treatments and more directed education efforts to combat what epidemiologists suspect could be the highest colorectal cancer rates in the world. 

“Our research will add a piece to this puzzle,” said Ulrike Peters, a Fred Hutchinson molecular and genetic epidemiologist and one of the principal investigators on the research funded by a $3.6 million grant from the National Cancer Institute. This research looks at addressing health disparities in Alaska Native, Black, and Hispanic populations. “We really need to study what is driving these disparities.”

Discovering a hidden gap

US cancer data hasn’t always reflected the high occurrence of colorectal cancer and deaths among Alaska Native peoples. 

That’s because Alaska Native peoples are typically grouped with American Indians, despite significant differences in lifestyle and diet. That grouping has masked the high rates, since other American indigenous groups experience much lower figures. When Alaska Native figures are separated, their numbers reveal a striking disparity that cannot be explained by factors like sample size or additional screenings, researchers say. 

In its 2017–19 report, the American Cancer Society validated these findings on a national scale by including a separate graphic that separated Alaska Natives from Indian tribal groups and noted that the Alaska Native rates were the highest in the country, said Diana Redwood, a senior epidemiologist with the Alaska Native Epidemiology Center.

“It’s been heartening to me to see that national reports are starting to acknowledge this difference,” she said.

Indeed, the most recent report from the American Cancer Society describes the “alarming” burden of colorectal cancer among Alaska Native people with incidence rates of 89 per 100,000—the highest in the country. The incidence rate for Alaska Native people is more than double the rate for the combined Alaska Native/American Indian grouping, which is about 43 per 100,000.

Finding ‘something more’

Certain factors are thought to contribute to increased risk of colon cancer such as low dietary fiber, vitamin D deficiency, smoking, obesity, and diabetes. A high prevalence of a certain bacteria that is linked with inflammation could also be a risk factor. But the cause of the disparity among Alaska Native peoples is unknown. Some factors that might be more prevalent in Alaska include environmental components, such as high indoor pollution and disrupted sleep patterns stemming from the long, dark winters and limited darkness in the summer. Amid Alaska’s vast geographic territory, people in some regions might struggle to access treatment, screening, and a trusted health care provider.

“I can’t help thinking there is something more,” Redwood said. Other scientists working on this research project agree. 

The team is taking a closer look at the genes and microbiome of tumors. They want to know whether someone’s genes, the community of bacteria in their tumor, or the interplay between the two could cause more rapidly advancing cancer. For example, the microbiome could impact how some genes turn on or off. If researchers can identify whether certain microbes enable the tumor to advance more rapidly, the findings could lead to interventions, from fiber supplements to drugs like immune inhibitors.

The role of the microbiome and its impact on human health is an emerging area of research that has been studied mostly in people of European descent, Peters said. This will be the first study to look at cancer tumors from Alaska Native peoples on a molecular level.

Given what they’ve seen so far, Peters is optimistic some differences will be found. Along with helping the Alaska Native populations, the research could also encourage further study of health disparities.

“This is a stepping-stone to building a larger program,” she said.

Establishing community support

The research is a high priority for health leaders in the community, said Dr. Timothy Thomas, a physician and research director of the Alaska Native Tribal Health Consortium.

“It’s very much on people’s minds,” he said. “We hear it from tribal health organizations around the state—it’s a frequent item of discussion.”

The project has also been well received in the community, something Redwood attributes to a genuine curiosity about the high rates. Redwood has ferry hopped from village to village, sometimes bringing along an inflatable colon people can walk through. Humor helps ease discomfort around a potentially uncomfortable—but important—topic, she said.

Public health workers use a giant inflatable colon at outreach events to better explain their message. The giant colon makes the disease more tangible and easier to talk about, says epidemiologist Diana Redwood. (Photo courtesy: The Alaska Native Tribal Health Consortium)

Tackling this disparity broadly will require culturally responsible efforts that align with community values, noted professor and researcher Jordan Lewis, an Alaska Native who studies healthy aging and is not involved with the project. For one, there is a sense—especially among community elders—that the colon is not something to be openly discussed. That hesitation can lead to a reluctance to get colon cancer screenings even if they are readily available.

“It’s pretty private,” Lewis said, noting he is not sure he would even discuss colon screenings with his own family.

There’s also historic mistrust of medical researchers, stemming from a long legacy of abusive health interventions and research that has exploited native populations. Greater indigenous representation in research and medicine would go a long way in addressing these deep-seated suspicions, Lewis said.

It is also important to understand the cultural mindset of valuing community over the individual, he added. For example, an elder might be more receptive to colon cancer messaging that focuses on the future of loved ones, instead of their own personal health. 

That messaging resonates with Fox, the Alaska Native who lost his mom to colorectal cancer. Fox, 50, now educates his own children on the importance of fruits and vegetables and a high fiber diet, actions that create a protective effect. He is optimistic that researchers’ findings from this study and others will give people more tools to fight this troubling disparity.

When Fox reflects upon the long history of Alaska Native communities, he thinks about how hard his ancestors fought against threats to their livelihood and survival.

“I don’t understand why we are not at war with this,” he said. “If we keep working at this, lives will be saved.”