Shuji Ogino’s team presents a comprehensive review of the risk factors, molecular features, and clinical characteristics of early-onset cancers.
Distinct risk-factors are emerging for various cancer types: esophageal (adenocarcinoma: obesity, GERD, smoking; poor oral hygiene, hot beverages, second-hand smoke), gastric (H. pylori, high-sodium diet, alcohol, smoking, CDH1 variants), colorectal (obesity, sedentary behavior, metabolic syndrome, red meat, alcohol, low vitamin D, microbiome links), biliary tract (biliary cysts/stones, HBV/HCV, pancreaticobiliary maljunction, PARP1 variants), liver (chronic HBV, metabolic conditions, smoking, SPRTN variants), pancreatic (smoking, obesity, diabetes, tall height, non-O blood group, DNA repair variants), kidney (obesity, family history, FH/VHL/MET variants), prostate (high-fat diet, BRCA1/2, HOXB13, DNA repair genes), endometrial (obesity, hyper-oestrogenic states, nulliparity, CTNNB1 mutations), and breast (early menarche, nulliparity, alcohol, physical inactivity, BRCA1/2).
It is reported, that early-onset head and neck cancer predominantly affects the tongue and oral cavity, carries a generally favorable prognosis except for hypopharyngeal tumors. Key risk factors include smoking, alcohol, HPV infection (especially for oropharyngeal tumors), low fruit/vegetable intake, and family history of early-onset cancers. Molecularly early-onset head and neck cancer is characterized by low EZH2 expression, activated MAPK/JAK-STAT pathways, oxidative stress signatures, and a distinct immune microenvironment enriched in tumor-associated macrophages, myeloid-derived suppressor cells, and plasma cells. These insights underscore the urgency for age-tailored prevention, screening, and molecular stratification.