Colonoscopic surveillance in familial colorectal cancer

Sammanfattning: Colorectal cancer (CRC) is a disease with a high and rising incidence in the industrialized countries. It is the third leading cause of death among cancers in Sweden and the forth worldwide. Important etiological factors are both environmental and lifestyle as well as heritable factors. Familial adenomatous polyposis (FAP) and Lynch syndrome (LS) with known mutations in single high-penetrance genes account for 2-4% of the CRC cases, leaving a large group with familial clustering of CRC without known genetic background. In the majority of cases, CRC seems to be preceded by a benign lesion, the adenoma, which can be detected and removed during a colonoscopy, making prevention feasible. For FAP and LS there are well-established endoscopy prevention programmes, but for the large group with familial clustering these programmes have to be evaluated and risk profiles have to be identified. In an attempt to determine the prevalence of colonic neoplasia in the normal population with average risk for CRC, 745 randomly selected individuals aged 19-70 volunteered for a colonoscopy. One in ten had an adenoma and 2.8% had an advanced lesion but no cancers were discovered. The results may provide a control population for further studies (Paper I). In a European multi-centre study, colonoscopy surveillance in 530 families with familial CRC with a dominant family history of CRC was evaluated. At baseline, 22 (1.4%) prevalent asymptomatic colorectal cancers were diagnosed, 120 (7.6%) individuals had high-risk adenomas and 225 (14.2%) simple adenomas. Interval cancers, more often seen in individuals that have had multiple adenomas, were infrequent, but the incidence of high-risk adenomas and multiple adenomas was high during surveillance. The study resulted in a suggestion of a screening interval of five years, that would be shortened if multiple and/or advanced adenomas occurred (Paper II). The findings at the screening colonoscopy in a population with increased risk of CRC due to family history were compared to the control population in Paper I. The risk population was stratified into four groups: LS, FCRC, TCR and OCR. In LS, 30% of the individuals had adenomas and 10% advanced adenomas. The corresponding figures in the other three risk groups were 14-24% and 4-7%, compared to 10% and 3% in the control group. In three of the four subgroups, the relative risk for adenomas as well as for advanced adenomas was significantly higher than in the control group. Individuals with a family history of colorectal cancer had high prevalence and cumulative risk of adenomas and advanced adenomas, indicating that colonoscopy screening is beneficial in this population (Paper III). In a cohort with an at least twofold increased risk of CRC due to family history, the impact of various family history variables on the prevalence of adenomas and advanced adenomas was assessed. Furthermore, the association between findings at the first colonoscopy and risk of future lesions was studied. The most important risk factors for advanced lesions including cancer at the screening colonoscopy were the number of first-degree relatives and a young family member with CRC. Finding of simple adenomas or hyperplastic polyps at the screening colonoscopy did not seem to predict for subsequent advanced adenomas or cancers (Paper IV).