Field synopsis of environmental and genetic risk factors of sporadic early-onset colorectal cancer and advanced adenoma

Background: To systematically appraise and synthesize available epidemiological evidence on the associations of environmental and genetic factors with the risk of sporadic early-onset colorectal cancer (EOCRC) and early-onset advanced colorectal adenoma (EOCRA).

Methods: Multiple databases were comprehensively searched to identify eligible observational studies. Genotype data from UK Biobank were incorporated to examine their associations with EOCRC in a nested case-control design. Meta-analyses of environmental risk factors were performed and the strength of evidence was graded based on predefined criteria. Meta-analyses of genetic associations were conducted using the allelic, recessive, and dominant model, respectively.

Results: A total of 61 studies were included, reporting 120 environmental factors and 62 genetic variants. We found 12 risk factors (current overweight, overweight in adolescence, high waist circumference, smoking, alcohol, sugar beverages intake, sedentary behavior, red meat intake, family history of CRC, hypertension, hyperlipidemia and metabolic syndrome) and three protective factors (vitamin D, folate, and calcium intake) for EOCRC or EOCRA. No significant associations between the examined genetic variants and EOCRC risk were observed.

Conclusions: Current evidence indicates that changing patterns of traditional CRC risk factors may explain the rising incidence of EOCRC. However, research on novel risk factors for EOCRC is limited and therefore we cannot rule out the possibility of EOCR having different risk factors than older onset CRC.

Impact: The potential for the identified risk factors to enhance the identification of at-risk groups for personalized EOCRC screening and prevention and for the prediction of EOCRC risk should be comprehensively addressed by future studies.