Role Of Cytokine Gene Polymorphism and Interaction of Diet and Nutrition with Genetic Susceptibility in Colorectal Adenocarcinoma

Abstract

Colorectal cancer (CRC), one of the leading causes of cancer-related deaths globally, presents a growing health challenge not only in Western countries but also in rapidly urbanizing nations like India. While traditionally associated with older adults, CRC is now increasingly being diagnosed in younger populations under the age of fifty, raising serious public health concerns. This multifactorial disease arises from a complex interplay of genetic predispositions, lifestyle factors, dietary habits, and environmental exposures. This review explores the role of cytokine gene polymorphisms, dietary methylation pathways, promoter hypermethylation of tumor-suppressor genes, and the polymorphic variants in detoxification genes like NAT1 and NAT2, in contributing to colorectal cancer susceptibility. We delve into how chronic inflammation and individual genetic makeup influence cancer risk, especially in the context of common inflammatory cytokines like IL-6, IL-10, TNF-α, and TGF-β. Additionally, we highlight how Western dietary patterns—characterized by low folate and high alcohol and red meat intake—may amplify this risk through epigenetic and metabolic disruptions. Importantly, we examine the unique landscape of CRC in India, where dietary transitions, genetic diversity, and environmental influences offer a distinct context to understand gene-environment interactions. With a growing body of evidence suggesting that certain genetic variants may alter an individual’s risk based on diet and lifestyle, this paper underscores the need for more region-specific research to inform early detection strategies, preventive interventions, and personalized treatment approaches.