Sweetened drinks, sugar intake up incidence, mortality of proximal colon cancer

Consumption of sugar and sugar-sweetened beverages (SSBs) appears to increase proximal colon cancer incidence and mortality, particularly during later stage of tumorigenesis, reports a study.

“Although requiring confirmation in other large cohorts, these observational data support findings from a recent animal study that suggested a direct tumour-enhancing role of dietary sugars in colorectal tumorigenesis,” according to the researchers, led by Chen Yuan from the Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, US.

The study sought to assess long-term intake of SSBs and total fructose with respect to the incidence and mortality of colorectal cancer (CRC) by anatomic subsite. The researchers followed a total of 121,111 participants form two prospective US cohort studies, the Nurses’ Health Study (1984‒2014), and the Health Professionals Follow-Up Study (1986‒2014). They estimated the hazard ratios (HRs) and 95 percent confidence intervals (CIs) using Cox proportional hazards regression.

Overall, 2,733 incident cases of CRC with a known anatomic location were recorded during follow-up, with 901 succumbing to the disease. SSB and total fructose intakes positively correlated with cancer incidence and mortality in the proximal colon, but not in the distal colon or rectum (p<0.03 for heterogeneity). [Am J Clin Nutr 2022;115:1481-1489]

SSB intake correlated with a statistically significant increase in the incidence of proximal colon cancer (HR per 1-serving/d increment, 1.18, 95 percent CI, 1.03‒1.34; p_trend=0.02) and a more pronounced elevation in mortality (HR, 1.39, 95 percent CI, 1.13‒1.72; p_trend=0.002). Total fructose consumption also resulted in an increased proximal colon cancer incidence (HR per 25-g/d increment, 1.18, 95 percent CI, 1.03‒1.35) and mortality (HR, 1.42, 95 percent CI, 1.12‒1.79).

In addition, consumption of SSB and total fructose during the most recent 10 years contributed to an increased incidence of proximal colon cancer compared to those from a more distant period.

“[O]ur results provide further support for current dietary guidelines and policies to limit SSB consumption to improve the health of the general population,” the researchers said.

Overwhelmed intestine

Notably, the association observed in this study was restricted to the proximal colon, specifically the cecum, which is closest to the small intestine. This could be partly explained by the direct proneoplastic action of unabsorbed fructose that reaches the colon, according to the researchers.

Moreover, hydrogen breath tests revealed that as little as 5‒25 g of fructose can overwhelm the absorptive capability of the small intestine in some healthy adults. [Gastroenterology 1983;84:26-29; J Am Diet Assoc 2005;105:1559-1566; Gut 1986;27:1161-1168]

“Another long-standing hypothesis on the oncogenic potential of dietary sugars relates to their contribution to systemic hyperinsulinaemia, insulin resistance, and dyslipidaemia, which have been implicated in colorectal carcinogenesis,” the researchers said. [Dig Dis Sci 2012;57:2497-2503; Lipids Health Dis 2019;18:29]

“Specifically, high glucose elicits rapid insulin release from pancreatic β cells, and a high flux of fructose to the liver, the main site of fructose metabolism, enhances triglyceride synthesis that in turn promotes hepatic and systemic insulin resistance,” they added. [Nutr Metab (Lond) 2005;2:5]