Early onset Colorectal Cancer: exogenous and endogenous associated factors

Raffaella Alessia Zuppardo1, Milena Di Leo2, Alessandro Mannucci1, Graziana Antoci1, Ilaria Ditonno1, Francesco Azzolini1, Dario Esposito1, Lorella Fanti1, Giorgia Mazzoleni1, Chiara Notaristefano1, Edi Viale1, Riccardo Rosati1, Pier Alberto Testoni1, Giulia Martina Cavestro1

1Gastroenterology and Gastrointestinal Endoscopy, Division of Experimental Oncology, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele Scientific Institute, Milan, Italy. 2Humanitas Clinical and Research Center, Department of Biomedical Sciences, Humanitas University, , Milan, Italy



Early onset colon and rectal cancer (eoCRC, <50 years of age) incidence is projected to increase by as much as 90% and 140%, respectively, by 2030, without single compelling explanation for this epidemiological trend. Germline mutations appear to account for only a fraction of these cancers (~20%) and do not explain increasing incidence.

We investigated the role of exogenous and endogenous risk factors associated to eoCRCs.

Methods EoCRC patients’ clinical, anamnestic and pathological data were retrieved prospectively from 2015 to 2018, and compared with a group of late onset CRC (loCRC) of same period.

Results We prospectively enrolled 54 eoCRCs and 494 loCRCs with a prevalence of females(59.3%) in eoCRCs and male prevalence in loCRCs(56.3%) (p=0.03). Diagnostic delay was higher in eoCRC group: only 40.0% of eoCRCs were diagnosed in the 6th months from symptoms onset versus 85.5% of loCRC patients (p<0.0001). Lynch syndrome was more frequent in eoCRC(8.3%) than loCRC group(0.8%), (p=.016). Smoking was also significantly different: no-smokers were 58.3% in eoCRCs and 39.5% of loCRCs (p=0.0178). A trend trough significance was present for no-drinker in eoCRCs and diabetes prevalence was 0% in eoCRC and 17.3%(p=0.001). Normal BMI was more frequent in eoCRC(94.1%)than in loCRC(60.1%) with a significant difference(p<0.001). Right colon CRC localization was more frequent in loCRC(9.3% in eoCRCs and 36.7% in loCRCs; p=0.0001).

Conclusion Diagnostic delay is associated to eoCRC. We confirmed exogenous variables as smoking habit and BMI act as cofactors in the development of loCRC.