In a recent article published in Nutrients, researchers evaluate the relationship between 139 dietary factors and the risk of developing colorectal cancer (CRC) using data from 118,210 participants in the United Kingdom (UK) biobank.
Study: Diet-Wide Association, Genetic Susceptibility and Colorectal Cancer Risk: A Prospective Cohort Study. Image Credit: aslysun/Shutterstock.com
CRC is the most common cause of cancer-related fatalities globally. Up to 65% of CRC cases are episodic, involving several modifiable risk factors, including poor diet and nutrition. Critically, approximately 20–25% of all global cancer cases are likely related to diet.
The European Prospective Investigation into Cancer and Nutrition (EPIC), a diet–scope–association study, found a positive correlation between alcohol intake and CRC risk and that modifiable lifestyle factors have varying effects on complex diseases, such as cancer. Likewise, genome-wide association studies (GWAS) have identified gene loci linked to CRC.
However, large-scale cohort studies examining the relationship between foods/nutrients and CRC or genetic–nutrition interactions are scarce. Thus, there is no concrete evidence favoring the prevention of CRC via dietary changes.
About the study
In the present study, researchers determined the prevalence and incidence of CRC in the large UK Biobank prospective cohort and its association with dietary intake of 139 foods and nutrients among 118,210 participants who completed their food nutrient intake via two online questionnaires.
In addition to a touchscreen questionnaire, they used Oxford WebQ, a self-administered 24-hour dietary questionnaire with nearly 200 questions on dietary consumption.
The team used a Cox proportional risk model for the association analysis, presenting results as hazard ratios (HRs) and 95% confidence interval (CI).
This model adjusted for age, gender, socioeconomic deprivation, education, family history of CRC, and several other potential confounding factors and stratified results by gender and cancer site.
A false discovery rate (FDR) was computed for multiple statistical comparisons, where p-values < 0.05 were considered significant.
Furthermore, the researchers created a polygenic risk score (PRS) for CRC risk of all study participants, which helped explore any interaction between dietary factors and genetic predisposition to CRC risk.
The researchers categorized them as low, intermediate, or high based on their tertile distribution among non-cases.
The literature search identified 1,466 incidents of CRC, of which 842 and 359 were colon and rectal cancers, respectively, during an average follow-up of 12.8 years.
The mean age of CRC patients was 55.87 years, and ~45% were male. Notably, overlapping colon lesions and undefined lesions characterized colon cancer, and that in the rectosigmoid node and rectum indicated rectal cancer.
The meta-analysis revealed that eight out of 139 foods were associated with CRC risk (FDRP < 0.05). While higher alcohol and white bread intake were associated with a higher risk of CRC, dietary fiber, calcium, magnesium, phosphorus, manganese, and carbohydrate intake were associated with lower CRC risk.
In categorical variable analysis, white bread and CRC risk showed a positive correlation, whereas the dietary fiber and minerals intake showed an inverse correlation with CRC risk. These associations remained statistically significant after FDR corrections.
Furthermore, the incidence rate of CRC gradually increased with increasing genetic risk. The multivariate-adjusted model results showed that compared to the low-genetic-risk group, the HRs of the high- and intermediate-genetic-risk group were higher, i.e., 2.55 and 1.61, respectively.
However, the study model found no evidence of any PRS–nutrient interaction relationship for CRC risk.
Because several evaluated nutrients have a common intake source, e.g., calcium and phosphorus, it was challenging to distinguish their independent roles.
However, the authors noted that the protective effect of manganese intake on CRC risk was robust even after multiple FDR corrections. Notably, manganese plays a crucial role in anti-tumor immune responses; however, more evidence is needed to verify this relationship.
Furthermore, observational results suggested that dietary fiber is a protective factor for CRC, as previous studies showed. Thus, it should be evaluated as an adjuvant preventative therapy for CRC.
This large prospective cohort study with a long follow-up period and utilizing a wide range of confounding factors confirmed the previously described positive association between alcohol and white bread and CRC risk.
Additionally, its results suggested that irrespective of the genetic makeup, intake of all the evaluated minerals and dietary fiber reduced CRC risk, whereas white bread increased this risk.
Overall, the study findings lend support to the dietary prevention of CRC. Future cohort studies might validate these results and further explore the associations between diet and CRC risk.
Jin, D.; Lu, Y.; Wu, W.; Jiang, F.; Li, Z.; Xu, L.; Zhang, R.; Li, X.; Chen, D. (2023) Diet-Wide Association, Genetic Susceptibility and Colorectal Cancer Risk: A Prospective Cohort Study. Nutrients. doi: https://doi.org/10.3390/nu15224801. https://www.mdpi.com/2072-6643/15/22/4801