— Two servings a day more than doubled risk in women younger than 50, study showed
by Diana Swift, Contributing Writer May 6, 2021

A higher intake of sugar-sweetened beverages (SSBs) in adulthood and adolescence was associated with an increased risk of early-onset colorectal cancer (CRC) in women, according to data from the Nurses’ Health Study II.

The prospective study followed 95,464 registered nurses from 1991 to 2015. Those consuming at least two SSB servings a day in adulthood had more than double the early-onset CRC risk of those consuming less than one serving a week (relative risk [RR] 2.18, 95% CI 1.10-4.35, P trend=0.02), reported Yin Cao, ScD, MPH, of Washington University in St. Louis, and co-researchers.

Furthermore, the risk rose by 16% with each additional serving per day. Strategies to reduce intake among adolescents and young adults could potentially alleviate the growing burden of the disease, the authors wrote in Gut.

In the adolescent years of ages 13 to 18, each serving-per-day increment was associated with a 32% higher risk of early-onset CRC (RR 1.32, 95% CI 1.00-1.75). In addition, replacing each SSB serving per day in adulthood with a serving of artificially sweetened beverages, coffee, or reduced-fat or total/whole milk was associated with a 17-36% lower risk.

“Considering the well-established, adverse health consequences of SSBs and the highest consumption being characterized in adolescents and young adults under age 50 years, our findings reinforce the public health importance of limiting SSB intake for better health outcomes,” the investigators wrote.

They noted that while CRC incidence has been on the decline in many high-income countries, the incidence of early-onset disease — that is, diagnosed before age 50 — has been on the rise over the past 2 decades. In the U.S. population born after 1950, the incidence of early-onset CRC has increased across subsequent birth cohorts, and compared with adults born around 1950, those born around 1990 had twice the risk of colon cancer and four times the risk of rectal cancer.

National Health and Nutrition Examination Survey data show that an estimated 12% of the U.S. population currently consume more than three SSB servings per day.

In the study by Cao and co-authors, the population consisted overwhelmingly of white females, ages 25 to 42, with an average age of approximately 42 at enrollment. Over up to 24-plus years of follow-up (1,358,142 person-years), 109 incident cases of early-onset CRC occurred.

The researchers found that individuals with higher SSB intakes in adulthood tended to be less physically active and more likely to have a lower endoscopy history, to use non-steroidal anti-inflammatory drugs, and consume red and processed meats. Those with higher SSB intakes were also less likely to take multivitamins and to have lower intake of alcohol, fiber, folate, and calcium, and to have a poorer diet overall.

In line with previous research in older adults, no association was found between intake of artificially sweetened beverages or fruit juice in adulthood and risk of early-onset CRC.

Possible Mechanisms of Action

Cao and co-authors outlined several possible pathways for the effect of SSBs on early-onset CRC. For example, compared with isocaloric solid foods, energy-containing beverages that lack dietary compensation suppress feelings of satiety and promote excess energy intake and weight gain. SSBs initiate rapid blood glucose response and insulin secretion, which can induce insulin resistance, inflammation, obesity, and type 2 diabetes — metabolic conditions tied to increased CRC risk.

Other possibilities, the researchers said, include intestinal dysbiosis and endotoxemia caused by an excess of fructose, the principal sweetener in SSBs, which can impair gut barrier function and increase gut permeability, thereby potentially promoting carcinogenesis. For example, a recent experimental study suggested that high-fructose corn syrup promoted the growth of aggressive tumors in mice independent of obesity and metabolic syndrome.

Asked for his perspective, Lewis Cantley, PhD, director of the Meyer Cancer Center at Weill Cornell Medicine in New York City, who was not involved with the study by Cao and co-authors, called the new findings “exciting.”

In 2019, his group had published a study showing that high fructose corn syrup doubled intestinal tumor growth in mice. “In this case, the mechanisms, the enzymes and transporters, are the same as in humans,” Cantley explained. This animal research found that fructose and glucose act synergistically: “You have to have both. Fructose catalyzes glucose to grow the tumors,” he told MedPage Today.

Cantley noted that oncologists treating CRC have noticed an increase in the number of young “health enthusiasts” diagnosed with CRC: “They’re shocked to learn they have this cancer because they’re in great shape. They’re runners. They stick to vegetables and juices and eat little meat. But they may be drinking three glasses of fruit juice or sweet beverages every day to replenish their glycogen stores after running a couple of miles,” he said.

Overall, SSB intake has been trending downward in recent years, and Cao and co-authors concluded that further limiting consumption may be “an actionable strategy to curb the rising incidence of [early-onset] CRC.”

Study limitations, the researchers said, included possible residual or unmeasured confounding, that the low number of early-onset CRC cases prevented pinpointing the relevant time window of exposure, and that the low proportion of individuals with diabetes limited the power and feasibility to stratify by a personal history of diabetes. In addition, the study could not probe whether a similar association would be observed among individuals carrying pathogenic germline mutations identified in abut 20% of cases of early-onset CRC, and since the vast majority of participants were white female nurses, the findings may not be generalizable to men or to other racial/ethnic groups.