Smoking and risk of colorectal cancer according to KRAS and BRAF mutation status in a Japanese prospective Study.

This article focuses on the association between smoking and colorectal cancer risk according to tumor molecular subtypes defined by KRAS and BRAF mutation status in a Japanese population. Using data from the Japan Public Health Center-based (JPHC) prospective cohort study of 18,773 participants, the study found that ever smokers had an approximately twofold increased risk of KRAS wild-type colorectal cancer compared to never smokers, while no significant association was observed for KRAS-mutated or BRAF-mutated colorectal cancer. The findings indicate statistically significant heterogeneity in smoking-related risk by KRAS mutation status but not by BRAF mutation status, suggesting that smoking may influence colorectal cancer development through mechanisms other than KRAS mutations, potentially involving epigenetic modifications. This study provides novel evidence supporting smoking as a risk factor for specific colorectal cancer subtypes in Asian populations, highlighting the importance of molecular pathological epidemiology in understanding cancer etiology.