High intake of simple sugars and sugar-sweetened beverages during adolescence is associated with increased risk of conventional adenoma, especially rectal adenoma, researchers report in the July issue of Gastroenterology.
In contrast to the decreasing incidence of CRC in older populations, the incidence has nearly doubled in younger adults since the early 1990s. Approximately 1 in 10 new diagnoses of CRC are now made in individuals 50 years or younger. The higher incidence rates of early-onset CRC observed among those born in and after the 1950s and 1960s could be due to risk factors in early life (childhood and adolescence). Consumption of simple sugars, particularly fructose, has paralleled increasing incidence rates of early-onset CRC.
Hee-Kyung Joh et al examined the association between consumption of simple sugars (fructose, glucose, added sugar, total sugar), including sugar-sweetened beverages, and risk of colorectal neoplasia (total adenoma, proximal adenoma, rectal adenoma, and high-risk adenoma)—particularly early-onset (younger than 50 years)—using data from 33,106 participants in the Nurses’ Health Study II.
Joh et al found that high intake of sugar and sugar-sweetened beverages during adolescence was associated with increased risk of adenoma. After adjustment for dietary covariables (adolescent fruit, fiber, and calcium intake), the odds ratios of total adenoma were 1.17 (95% CI, 1.05–1.31; Ptrend = .006) per each increment of 5% of calories from total fructose intake and 1.11 (95% CI, 1.02–1.20; Ptrend = .01) per 1 serving per day of sugar-sweetened beverage intake.
The multivariable odds ratio of high-risk adenoma was 1.30 (95% CI, 1.06–1.60; Ptrend = .012) per 5% of calories from total fructose intake. Higher adolescent sugar-sweetened beverage intake (per 1 serving per day) was significantly associated with high-risk rectal adenoma (odds ratio, 1.34; 95% CI, 1.01–1.79; Ptrend = .044).
By subsite, odds ratios were 1.12 (95% CI, 0.96–1.30) for proximal adenoma, 1.24 (95% CI, 1.05–1.47) for distal adenoma, and 1.43 (95% CI, 1.10–1.86) for rectal adenoma.
Contrary to adolescent intake, sugar and sugar-sweetened intake during adulthood was not associated with adenoma risk. Joh et al explain that adolescence seems to be a critical developmental period for susceptibility to the adverse effects of high sugar intake. Adolescence is a period of high cell proliferation, distinct hormonal and metabolic changes, decreased insulin sensitivity, and increased levels of IGF1, which might be altered by high sugar intake to contribute to carcinogenesis.
Intake of sugar or sugar-sweetened beverages during adolescence were not associated with risk of total or large serrated lesions. Joh et al therefore propose that high sugar intake during adolescence may be etiologically more important for CRC arising from the conventional adenoma to carcinoma sequence vs the serrated neoplasia pathway.
Simple sugar intake during adolescence was more strongly associated with adenoma diagnosed at <55 years, supporting the link between early-life diet and earlier initiation of colorectal carcinogenesis. In an editorial that accompanies the article, Jeffrey K Lee et al write that younger birth cohorts consumed more fructose and sugar-sweetened beverages during adolescence, compared with older birth cohorts, indicating the importance of focusing analyses of early-onset CRC on generational trends in risk factors. A previous study found smoking, alcohol intake, obesity, and metabolic syndrome to be significant risk factors for young-onset colorectal neoplasia.
Results for glucose (from simple sugars), added sugar, and total sugar were similar to the results for total fructose, but effect sizes were slightly smaller than for total fructose. Neither artificially sweetened beverage nor fruit juice intake was associated with risk of adenoma.
Positive associations between sugar intake and adenoma risk were significantly stronger among women with low fruit intake (<1.3 servings per day) during adolescence than women with high intake (≥1.3 servings per day). Associations of fructose and sugar-sweetened beverage intake with adenoma risk did not differ significantly with family history of CRC, birth year, adolescent body mass index, physical activity, smoking, or alcohol consumption.
Substituting 2 servings per day of dairy products for 2 servings per day of sugar-sweetened beverages was associated with lower risk of rectal adenoma (odds ratio, 0.53; 95% CI, 0.30–0.94).
Joh et al found stronger associations among women with unhealthy diet patterns (low prudent and high Western) during adolescence than women with healthy diet patterns. So, excessive sugar intake might promote colorectal carcinogenesis when combined with overall unhealthy dietary patterns, by exacerbating chronic insulin resistance.
How might sugary drinks promote colorectal carcinogenesis? Joh et al propose several mechanisms, including the effects of sugars on the intestinal microbiome, which could affect CRC development via immune system, metabolic, and epigenetic effects.
The authors state that this was the first prospective study investigating the role of high sugar intake during adolescence in risk of colorectal polyps. Dietary data were collected before endoscopic procedures and polyp diagnoses, minimizing the potential of recall bias. Limitations include possibility of measurement error in adult recall of adolescent diet. However, the high school food frequency questionnaire (HS-FFQ) used has reasonable reproducibility and validity.
Joh et al conclude that high intake of simple sugars and sugar-sweetened beverages during adolescence is significantly associated with increased risk of total and high-risk adenoma, especially rectal adenoma. There has been a large increase in added sugar and sugar-sweetened beverage intake during the past several decades, so these findings might account for the trend in increasing early-onset CRC. Further prospective studies, using valid information on early-life diet in other populations, are needed to confirm these findings.