Hereditary colorectal cancer : Predisposition and prevention
Sammanfattning: This thesis focuses on the clinical results from a ten-year long follow-up surveillance program, including regular colonoscopy, for subjects (n=304, 780 colonoscopies) with increased risk of colorectal cancer, and on psychological aspects of the program. The cohort included persons with hereditary nonpolyposis colorectal cancer (HNPCC) and persons assumed to be at increased risk of colorectal cancer because they had two (Two close relatives, TCR) or three or more relatives (Hereditary colorectal cancer, HCRC) afflicted with colorectal cancer. In addition, an international cohort of subjects with HNPCC (n=532) was evaluated regarding the prevalence of adenomas and hyperplastic polyps. In paper I we found a significantly increased risk of developing an adenoma before the age of 54 years in all risk groups as compared with a reference population (three autopsy studies). We found no significant differences with respect to prevalence of adenomas between the three family types or between sexes. However, the age of onset of the adenomas was earlier and the grade of dysplasia was higher in adenomas in HNPCC than in the other groups, HCRC and TCR. In paper II we found a significant positive correlation between the numbers of hyperplastic polyps and adenomas in the whole study population and a similar correlation was seen in all three family types as well as during follow-up. Predictors for the detection of adenomas and hyperplastic polyps were increasing age and observation time. A positive finding of either a hyperplastic polyp or an adenoma at first colonoscopy was a predictor for future findings of both types of colon polyps. In paper III we found that the average perceived benefit of regular colonoscopies rated 8.0 on the visual analogue scale (VAS range 1-10). There was a wide range of risk perception and 61% of the mutation carriers reported their personal risk as being 40% or less. Increasing age and a longer surveillance (increased number of colonoscopies) were significantly and positively associated with less discomfort. All HAD anxiety and depression values were within the normative data range. The measurement of quality of life (SF-36) showed significantly lower values regarding mental health among males, and vitality among females as compared with the general population. In paper IV we found that the prevalence of adenomas and hyperplastic polyps among HNPCC individuals was 18% and 10%, respectively. A significant positive correlation was found between the adenomas and hyperplastic polyps in the whole study population. In summary, individuals with increased risk of colorectal cancer due to hereditary factors run a greater risk of developing adenomas than the general population. The majority of the population at risk tolerates regular colonoscopies well. The correlation between adenomas and hyperplastic polyps found in this population indicates that hyperplastic polyps may act as a marker for mutation carriers and should be taken into consideration when screening programs are designed.
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