What causes colorectal cancer in the young? Insights from an age-specific attributable fraction analysis.

The incidence of colorectal cancer (CRC) among adults under 50 years has been increasing, but the contribution of lifestyle and medical risk factors in this population remains unclear. We estimated population attributable fractions (PAFs) and the corresponding number of CRC cases in the USA in 2022 attributable to tobacco smoking, alcohol drinking, overweight and obesity, physical inactivity, diabetes, hypertension, red and processed meat intake, and calcium and fiber intake across three age groups: 30-49, 50-69, and ≥70 years. Birth-cohort-specific prevalence data were obtained from National Health and Nutrition Examination Survey (1999-2002), relative risks from meta-analyses, and CRC incidence from Global Cancer Observatory 2022. PAFs were calculated using Levin's and the standard formula, stratified by gender and age group. The combined contribution of lifestyle and medical risk factors was greater in early-onset colorectal cancer than in the older age groups, largely driven by lifestyle-related exposures. Combined, they explained 61.4% of young-onset, 55.2% of middle-aged, and 56.4% of older-onset CRC cases. Low-fiber intake (16.7%), tobacco smoking (PAF 16.3%), and alcohol drinking (15.6%) were the leading contributors in the young, followed by obesity (7.8%). Medical factors, including diabetes and hypertension, exerted a small contribution in the young, which increased with age. Gender-specific analyses revealed higher tobacco smoking-attributable PAFs in young men and higher obesity-related PAFs in young women. Over half of cases in the young in the USA are attributable to known risk factors, most of which are potentially preventable. These findings contribute to understanding the distinct etiology of early-onset CRC and highlight the need for age-specific prevention strategies.