“It is not death that a man should fear, but he should fear never beginning to live.”
— Marcus Aurelius.
Over the last several decades, chronic diseases like Type II Diabetes have been increasing in prevalence in increasingly younger age groups. Unfortunately, several types of cancers have been doing the same. Among them is Early-Onset Colo-Rectal Cancer (EOCRC; colorectal cancer diagnosed before age 50). This is not a phenomenon limited to the US or industrialized nations; it is increasing globally. What appears different about EOCRC is that, unlike other cancers, where a family history helps identify risk, EOCRC often occurs in individuals without family history or identifiable genetic predisposition to colorectal cancer(CRC).
This suggests that modifiable environmental and lifestyle exposures may contribute substantially to the risk of its development. In fact, obesity, sedentary lifestyle, type 2 diabetes (T2D), and diets low in fiber and high in processed meats and added sugars are just such recognized risk factors. These dietary characteristics are hallmarks of ultraprocessed foods (UPFs). These foods now account for 60-70% of the average US adult’s daily energy intake, with higher percentages seen in the younger age groups.
Is there a connection?
This week’s Study Spotlight examines a prospective study that addresses this question.
- This study analyzed data of 29,105 female participants from the Nurses’ Health Study II, an ongoing US prospective cohort of registered nurses established in 1989, with a follow-up from June 1, 1991, through June 1, 2015.
- Dietary intake and UPF consumption (NOVA Group 4) were determined by a food frequency questionnaire.
- Participants underwent at least one lower endoscopy before age 50 years and had no history of cancer or colorectal polyps.
- Analysis focused on the incidence of EOCRC precursors (not actual EOCRC), including conventional adenomas and serrated lesions, confirmed via medical records and pathology reports.
- UPFs provided 34.8% of total daily calories with a median of 5.7 (interquartile range, 4.5-7.4) servings per day (significantly lower than the 60-70% for the average US adult).
- Participants with higher UPF intake showed a 45% increased risk for early-onset conventional adenomas, but not serrated lesions.
- The findings remained consistent after adjusting for BMI, T2D, dietary factors (fiber, folate, calcium, and vitamin D), and the Alternative Healthy Eating Index-2010 score.
The Caveat:
What is fascinating about this study is the intent and the findings. The study set out to examine UPFs and their potential impact or correlation with the risk of developing EOCRC. According to the authors, the study was unable to directly evaluate the risk of EOCRC due to insufficient statistical power from the limited incident cases. Thus, what was found and serves as the title is Ultraprocessed Food Consumption and Risk of Early-Onset Colorectal Cancer Precursors Among Women. In other words, there was not enough evidence to establish a link between eating ultraprocessed foods and the risk of EOCRC. But if we dig deeper, this becomes a classic case where the absence of evidence is not evidence of absence.
A takeaway from the study is why the researchers were unable to answer the question they set out to address. The answer is that the incidence of EOCRC was too low; there were far fewer cases than the researchers had predicted. A likely explanation involves the fact that this group, consisting of health professionals (Nurses), consumed about half as much UPF as the average American (34.8% versus 60-70%). As a group, their intake of UPFs was consistently in this lower range, dating back to study onset in 1991 (supplemental data, eFigure 3). Thus, the study examined a group of comparatively low-UPF consumers within the total US population. In other words, looking at the bigger picture, the low incidence of EOCRC in this group may actually support the hypothesis that UPF consumption increases the risk of EOCRC. An opposite conclusion can be drawn from the initial observation that UPF consumption (in this study) was associated with so few cases of EOCRC as to be meaningless, which we might properly label a null finding (there are so few instances of EOCRC that no meaningful conclusions can be drawn either for or against the hypothesis that UPF consumption tracks directly with EOCRC incidence prospectively).
The study did find a 45% increased risk of early-onset conventional adenomas in the highest quintile of UPF consumers compared with the lowest. Unfortunately, the study defined quintiles by ‘servings of UPFs per week,’ and does not explicitly define energy-adjusted servings per day in terms of the percentage of total energy consumed or the percentage of total food consumed in grams per day. This reduces the extractability of the findings to a general population. Of note, the researchers did report that “ Within UPF subgroups, no single food group appeared to drive the overall association of UPF intake, suggesting that the combined exposure to multiple food additives may exert a synergistic or cocktail effect on gut health by impairing barrier function and altering the microbiome.” What we are left with is the takeaway that eating more ultraprocessed food increases your risk of early-onset colorectal conventional adenomas.
The Study:
Additional references:
Akimoto N, Ugai T, Zhong R, et al. Rising incidence of early-onset colorectal cancer—a call to action. Nat Rev Clin Oncol. 2021;18(4):230-243. doi:10.1038/s41571-020-00445-1
Monteiro CA, Cannon G, Levy RB, et al. Ultra-processed foods. Public Health Nutr. 2019;22 (5):936-941. doi:10.1017/S1368980018003762
Monteiro CA. Nutrition and health: the issue is not food, nor nutrients, so much as processing. Public Health Nutr. 2009;12(5):729-731.doi:10.1017/S1368980009005291
Stoffel EM, Murphy CC. Epidemiology and mechanisms of the increasing incidence of colon and rectal cancers in young adults. Gastroenterology. 2020;158(2):341-353. doi:10.1053/j.gastro.2019.07.055
