Early-Onset Colorectal Cancer : Risk Factors and Outcomes

Colorectal cancer is one of the most common and lethal forms of cancer, and the Western world is experiencing an increase in the incidence among adults aged under 50 years. Up to one third of these patients, referred to as ´early-onset colorectal cancer´ (EOCRC) have a family history of the disease. Lifestyle-related risk factors and a personal history of inflammatory bowel disease (IBD), such as ulcerative colitis and Crohn’s disease, are other important risk factors. The aim of this thesis was to explore hereditary and non-hereditary risk factors associated with early-onset colorectal cancer (EOCRC) and to study the outcomes for patients with IBD coinciding with colorectal cancer. Study I was a population-based observational study that evaluated the awareness of hereditary colorectal cancer, measured by the number of patients referred for genetic counselling. Patients diagnosed with EOCRC in the South-Eastern Healthcare Region of Sweden from 2008 to 2017 were included, and all electronic medical records were reviewed. Of the 278 patients, 116 (42%) had been referred to genetic counselling, among whom 74 (64%) completed their genetic investigation. In 13 (18%) patients, a germline mutation was found. Studies II, III, and IV used the Swedish Colorectal Cancer Database as a data source, which provided multi-linkage between several national health registers. Study II was a case– control study of non-hereditary risk factors, such as metabolic and autoimmune disorders, and their association with EOCRC. The study examined data from 2,626 patients with EOCRC who were diagnosed in Sweden between 2007 and 2016, along with 15,759 comparators matched for age, sex, and county of residence. Metabolic disease nearly doubled the incidence of EOCRC, and IBD was associated with a sixfold increase in the incidence of EOCRC. Presence of non-inflammatory bowel disease was not associated with an increased incidence of EOCRC. Study III compared the recurrence-free survival (RFS) rates for patients who underwent surgical resection for rectal cancer, diagnosed between 1997 and 2021, with or without IBD. Flexible parametric survival models were used and were adjusted for time since surgery, year of diagnosis, sex, age at diagnosis, and Charlson comorbidity index score. Of the 22,082 patients included, 323 (1.5%) had IBD. Neoadjuvant radiotherapy and chemoradiotherapy were administered to 55% and 63% of patients, respectively. The overall RFS was similar between the groups (HR 1.05, 95% CI 0.87–1.26); however, a poorer RFS was observed during the first year after surgery (1-year HR 1.36, 95% CI 1.06–1.73) in patients with IBD. Study IV compared the overall survival, RFS, and cancer-specific survival rates for patients with and without IBDs, who were diagnosed with colon cancer from 2007 to 2021 and surgically resected with curative intent. The Cox proportional hazards model was used, adjusted for sex, age, date of colon cancer surgery, Charlson comorbidity index score, and primary sclerosing cholangitis. Among the 35,640 patients studied, 675