Esophageal cancer is a highly fatal disease with a very poor prognosis. There are two main histologic subtypes of esophageal cancer – squamous cell carcinoma (SCC) and adenocarcinoma (AC) – with distinct etiologies and phenotypes. Diet factor is one of the risk factors for esophageal cancer. Poor diet combined with the rising of obesity increase the crosstalk between hyperinsulinemia and inflammation, key factors in cancer development. The reversed empirical Dietary Index for Hyperinsulinemia (rEDIH) and reversed Empirical Dietary Inflammatory Pattern (rEDIP) are two metabolic dietary patterns developed to measure the ability of whole diets to influence these two mechanisms. Both rEDIH and rEDIP have been associated with several cancers in multiple cohorts, and they have previously exhibited stronger associations with lower risk of cancers than dietary patterns based on general healthy eating. However, the evidence of rEDIH and rEDIP on esophageal cancer is limited. The individual genetic background plays a crucial role in esophageal carcinogenesis. Polygenic risk scores (PRS) estimate an individual’s genetic susceptibility to specific biological functions or diseases by aggregating the combined effects of multiple risk-associated genetic variants. PRS is valuable for clinical applications and enables personalized dietary recommendations.
This study aims to investigate the interaction between a PRS reflecting multiple esophageal cancer risk factors and rEDIH and rEDIP. These diet-gene interactions may benefit the targeted dietary interventions tailored to individuals based on their genetic susceptibility.
Aim 1. Measure the association of rEDIH/rEDIP with esophageal cancer risk (overall esophageal cancer, esophageal SCC, esophageal AC) in UK Biobank.
Aim 2. Measure effect modification of the association of rEDIH/rEDIP with esophageal cancer risk by genetic variants in key pathways in esophageal cancer (esophageal SCC, esophageal AC).
