Thursday, December 08, 2022

I was recently on a Zoom call at work when I realized that one of my colleagues was calling from Dublin. It turned out she was dropping her daughter off at Trinity College to start her school year. I had two images as I thought of Trinity College, one of the great universities in the world. The first was of the students all sitting in a local pub eating bangers and mash along with a pint of Guinness. My second image was of Denis Burkitt, one of the great alumni of Trinity.

Denis Burkitt was born in Northern Ireland in 1911, lost an eye in an accident at age 11, and went to Trinity College, graduating with his medical degree in 1935, and then training as a surgeon. (How you do that with one eye seems remarkable to me!) During World War II, he was assigned to serve in Kenya and Somaliland. He was a religious evangelical Christian (he later became president of the Christian Medical Fellowship) and so after the War, believed that he had a calling to serve in Africa as a missionary-surgeon. He settled in Kampala in Uganda, where he had a clinic until 1964.

We should appreciate that many of our observations of geographic epidemiology (comparing the incidence of disease across nations to learn how variations in lifestyle may affect incidence of disease) have mostly centered on comparing East Asia, primarily Japan, to the West. Africa has been opaque to our discussions largely because good data and statistics on disease occurrence on that continent have been largely unavailable until quite recently, and certainly not in the time of Burkitt.

Burkitt himself proved to be an extremely astute observer and epidemiologist. He is best known for his observations and descriptions of large jaw tumors in children which proved to be aggressive lymphomas, later named after him (Burkitt’s lymphoma). But in this article, we focus on his other major set of contributions, highlighted by a paper he published in the Lancet in 1969 after his return to Great Britain in 1966. He reported that the population in his region of Uganda was characterized by a dearth of what we might now call the diseases of Western civilization—heart disease, diabetes, diverticulitis, appendicitis and most importantly, colorectal cancer—as compared to their prevalence in the U.K. He opined that this common reduction in incidence might share a common cause, and he attributed it to the differences in dietary fiber consumption between the two societies. Others had previously reported the importance of fiber, but what was novel about Burkitt was the lumping together of multiple diseases to a common cause. Further, at this point, he was world-renowned because of his lymphoma work so he was given widespread attention.

Burkitt reported in later papers that in Africa, the daily consumption of bran fiber was in the range of 50 grams while in the West it was 15 grams. The consequence (and he went back to Africa to show this) was large bulky stools in Africa versus small pellet-like stools in the West. Studies have also shown an impact of fiber on gut peristalsis, which could also potentially affect carcinogenesis. In 1979, he published a book called “Don’t Forget Fibre in Your Diet,” which became a bestseller.

So, have subsequent studies borne out Burkitt’s theories? As you may imagine, numerous observational studies, cohort and case-control, have been conducted in order to evaluate the association between dietary intake of fiber and colorectal cancer. We have previously discussed the difficulties of conducting dietary studies to assess cancer causality and the multiple problems that can arise. The same problems were true with assessment of fiber. The studies themselves have been inconsistent—some do find an association while others do not. But more importantly, fiber intake is confounded with multiple other factors. Since it is generally part of grain intake, then other constituents of grain may be responsible for an observed association. Prominent in this regard is folate intake. Or simply overall grain intake may be protective as opposed to fiber, one of its constituents.

It is disappointing that despite high interest for decades, the issue remains unresolved. While a randomized trial of fiber for colon cancer has never been done—the size would be enormous—a trial was conducted for adenomatous polyp recurrence. This is a popular design to test possible preventive agents. An old friend, Arthur Schatzkin, who was then head of the Nutritional Epidemiology Branch of NCI, led the Polyp Prevention Trial, published in the New England Journal of Medicine in 2000. It randomized 2,079 people with resected adenomas (who have a recurrence risk of about 30% at three years) to an intervention that consisted of low-fat (20% of total calories), high-fiber (18gms/1000 kcal), and 3.5 servings of fruits/vegetables/day versus no intervention for the controls. With repeat colonoscopy at four years, 39.7% of the intervention group and 39.5% of the control group had recurrent adenomas. What a disappointment this was for Schatzkin—and does not say much for fiber (or the other dietary interventions).

This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.

Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York.

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