February 22, 2019
Higher intake of whole grains and possibly cereal fiber and bran may be associated with reduced risk of hepatocellular carcinoma (HCC) among adults in the United States, according to a large observational study of two health professional cohorts with long follow-up.
Diet is suspected as a possible important risk factor for HCC, but only heavy alcohol use and certain fungus-contaminated foods (eg, affected nuts and spices) have been established as such, say study authors led by Xuehong Zhang, MD, ScD, Brigham and Women's Hospital and Harvard Medical School, Boston.
So the investigators turned their attention to other foods.
They focused on whole grains and dietary fiber, especially cereal fiber, because these have been associated with lower risk of obesity, type 2 diabetes, and nonalcoholic fatty liver disease — all of which are "known predisposing factors for HCC."
The team performed a cohort study among 125,455 participants from the Nurses' Health Study and the Health Professionals Follow-up Study and looked at the intake of whole grains, their subcomponents (bran and germ), and dietary fiber (cereal, fruit, and vegetable).
Study participants from both cohorts were scheduled to fill out food questionnaires every two years. Investigators divided study subjects into tertiles based on their levels of consumption of the study foods.
After an average follow-up of 24 years among the participants, there were 141 patients identified with HCC, which is a very low incidence cancer type.
The team reports that increased whole-grain intake was significantly associated with lower risk of HCC (the highest vs lowest tertile intake: hazard ratio [HR], 0.63; P = .04 for trend).
The findings were published online February 21, 2019, in JAMA Oncology.
An inverse HCC association was also observed for total bran (HR, 0.70; P = .11 for trend), but it was nonsignificant.
Additionally, increased intake of cereal fiber (HR, 0.68; P = .07 for trend), but not fruit or vegetable fiber, was associated with a reduced risk of HCC (but it was also nonsignificant).
"If our findings [are] confirmed, increasing whole-grain or possibly cereal fiber consumption may serve as a possible strategy for HCC primary prevention," said Zhang in an email to Medscape Medical News.
Medscape Medical News also asked another researcher who has studied diet and liver cancer to evaluate the new results.
Lemonica Koumbi, PhD, research fellow, Hepatology and Gastroenterology, Imperial College London, England, said the results showed that increased consumption of whole grains and bran and cereal fiber associates with lower HCC risk but not fruit or vegetable fiber.
"It is a powerful study with excellent statistical methods. Nevertheless the associations shown are not very strong so I would say promising evidence with potential," she told Medscape Medical News in an email.
Some Examples of These Foods
Asked for comment, Nicola McKeown, PhD, a nutrition epidemiologist at Tufts University, Boston, listed some examples of specific, easily purchased foods the investigators highlighted as possibly protective.
Whole grains, said McKeown, who was not involved in the study, include whole-grain breads and rolls, ready-to-eat breakfast cereals, cooked oatmeal, and cooked grains such as quinoa, brown rice, and millet.
Cereal fiber also includes ready-to-eat breakfast cereals (but not highly processed cereals that do not contain a lot of dietary fiber) and whole-wheat crackers.
And bran includes wheat bran, which is the main source of bran for most Americans.
"Eating more whole-grains as part of an overall healthy diet is a good dietary strategy for overall health, but more research is needed to ascertain how whole-grains, cereal fiber impact liver cancer," McKeown said in an email to Medscape Medical News.
She also pointed out that the new study is observational, "so causality cannot be inferred."
Other lifestyle factors were accounted for in the statistical models, said McKeown, but residual confounding is possible.
Koumbi offered an opinion about the possible mechanisms at work in the new findings. "Diets with a high fiber content, like cereals, may lower HCC occurrence by decreasing subjective appetite and energy intake and hence contributing to the maintenance of normal body weight as well as exerting beneficial effects on postprandial glucose level and blood lipid profile," she said.
The study authors hope that more research is performed in this area. They believe "future studies that carefully consider hepatitis B and C virus infections are needed to replicate our findings" and should examine these associations "in other racial/ethnic or high-risk populations."
Zhang commented that the participants in the two cohorts used in the new study were mostly white and that hepatitis infections are the most important risk factors for HCC, but were not prevalent in the current study population.
"Although our results showed no evidence of the differential association of whole grain and dietary fiber with the risk of viral and non-viral [HCC], or with the risk of cirrhotic and non-cirrhotic HCC, [the] small number of HCC cases may limit the statistical power and restrict further interaction analyses in these high-risk populations," he explained.
The study was funded by National Institutes of Health grants. One study author reports financial ties to Bayer, Janssen, and Pfizer.