Yohannes Adama Melaku

Ph.d

Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, South Australia

Senior Research Fellow

PLCO (Learn more about this study)

PLCO-1925

Jul 22, 2025

The Impact of Dietary and Ultra-Processed Food Consumption Patterns on Early-Onset Adult Colorectal Cancer Incidence and Mortality: A Prospective Cohort Analysis

Background: Early-onset adult colorectal cancer (CRC) incidence rates are on the rise globally (1) and these rates are projected to continue to rise in the ensuing years (2). Early-onset CRC disability-adjusted life years (DALYs) rates are gradually declining in both males and females in high SDI regions, except the USA, where the DALY rates are increasing in both males and females (2). In addition, CRC significantly impacts the global economy through medical expenses and loss of productivity (3, 4).
CRC development from precancerous lesions (conventional adenoma or sessile serrated lesions) is significantly influenced by the combination of the host genetics and environmental risk factors (physical, biological, chemical, or behavioural patterns) (5). Diet is one modifiable behavioural risk factors that has been linked with CRC through inflammation, immune function, oxidative stress, insulin resistance, and estrogen metabolism (6). We have postulated the PELICan (Perinatal and Early Life Influence on Cancer) hypothesis to explain the causation of early-onset adult cancers (7) and have found a significant impact of perinatal malnutrition (famine) on the risk of early-onset cancer in later life (8).
The relationship between diet and CRC risk and mortality (9) has been studied in several studies. The majority of research evaluated the impact of diet on CRC risk using a priori methods such as dietary scores or indices and limited studies used a posterior methods such as principal component analysis (PCA). Dietary scores/indices , however, cannot account for the interaction between various dietary components, indicate the overall dietary pattern, or provide particular information on multiple foods (10). PCA considers the interaction of different dietary components, but it does not consider the previous nutritional knowledge of how dietary intake links to CRC risk (11, 12). Therefore, improving the prediction of diet-related risk factors and CRC risks, requires further studies, including biomarkers to identify objective dietary patterns and novel statistical analysis methods which account for the interaction of nutrients and integrate previous nutritional knowledge with empirical data to provide further insights into the link between diet and CRC risk (6).
Currently, hybrid dietary pattern analysis methods which use existing subject matter knowledge to select intermediate response variables and dietary data to drive the dietary patterns have been recommended (13). Reduced rank regression is commonly used method among hybrid methods of dietary patterns analysis. It is used to identify a linear combination of food groups that explain as much variation as possible in a set of intermediate response variables (14). Therefore, we will use reduced rank regression analysis to identify and examine dietary patterns predictive of early-onset CRC risk in this analysis. We have previously demonstrated the successful use of this methodology to examine the association between dietary patterns and sporadic CRC risk and mortality (15).