Decoding the genetic and environmental forces in propelling the surge of early-onset colorectal cancer.
10.1097/CM9.0000000000003601
- Author:
Jianhui ZHAO
1
;
Haosen JI
1
;
Kangning LI
1
;
Guirong YU
1
;
Siyun ZHOU
1
;
Qian XIAO
2
;
Malcolm DUNLOP
3
;
Evropi THEODORATOU
3
;
Xue LI
1
;
Kefeng DING
2
Author Information
1. School of Public Health, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
2. Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310009, China.
3. Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh EH8 9DX, United Kingdom.
- Publication Type:Review
- Keywords:
Early-onset colorectal cancer;
Environmental factors;
Genetic factors;
Genome-wide association study;
Germline variants;
Interaction;
Lifestyle
- MeSH:
Humans;
Colorectal Neoplasms/etiology*;
Risk Factors;
Genome-Wide Association Study;
Genetic Predisposition to Disease/genetics*
- From:
Chinese Medical Journal
2025;138(10):1163-1174
- CountryChina
- Language:English
-
Abstract:
Early-onset colorectal cancer (EOCRC) shows a different epidemiological trend compared to later-onset colorectal cancer, with its incidence rising in most regions and countries worldwide. However, the reasons behind this trend remain unclear. The etiology of EOCRC is complex and could involve both genetic and environmental factors. Apart from Lynch syndrome and Familial Adenomatous Polyposis, sporadic EOCRC exhibits a broad spectrum of pathogenic germline mutations, genetic polymorphisms, methylation changes, and chromosomal instability. Early-life exposures and environmental risk factors, including lifestyle and dietary risk factors, have been found to be associated with EOCRC risk. Meanwhile, specific chronic diseases, such as inflammatory bowel disease, diabetes, and metabolic syndrome, have been associated with EOCRC. Interactions between genetic and environmental risk factors in EOCRC have also been explored. Here we present findings from a narrative review of epidemiological studies on the assessment of early-life exposures, of EOCRC-specific environmental factors, and their interactions with susceptible loci. We also present results from EOCRC-specific genome-wide association studies that could be used to perform Mendelian randomization analyses to ascertain potential causal links between environmental factors and EOCRC.
