AbstractIntroduction: Family history (FH) of colorectal cancer (CRC) is a frequent reason for referral to Clinical Genetics in the UK. The British Society of Gastroenterologists (BSG) guideline stratifies patients to risk categories (low/population, low-moderate, high-moderate and high) according to FH. Individuals with Lynch syndrome are classified differently to those who have a high-risk FH, but no high penetrance mutation. We investigated how effectively BSG guidelines categorise people at increased risk of CRC.
Methods: FH data was obtained for all unaffected people with a family history of CRC, referred to Tayside clinical genetics from 2000-2009. Risk category according to BSG guidance was assigned de novo. Individuals who went on to develop adenomatous polyps or CRC were identified by record linkage.
Results: 1120 patients were identified and after exclusion criteria, there were 728 non-polyposis patients (288 low-risk, 316 moderate-risk and 121 high-risk, including 31 mutation carriers). 8 invasive CRC developed, 2 in low, 3 in moderate and 3 in high-risk groups. There was no significant difference in the Relative Risk (RR) of cancer development between groups. The only significant finding was an increased risk of CRC in mutation carriers, RR 9.290 (1.3557- 63.6653). Kaplan-Meier analysis demonstrated no significant difference in cancer rates between groups. There was a significantly higher risk of polyp detection in the high-risk group compared to the low-risk group. Kaplan-Meier analysis demonstrated a significantly higher likelihood of polyp detection in the high-risk group when compared to both low and moderate-risk groups.
Conclusions: Presence of mutation seems to be the best predictor of cancer risk. Colonoscopic surveillance may be effective in reducing the cancer incidence in the moderate and high-risk groups. The study re-affirms that no colonoscopic screening is required in the moderate-risk group aged less than 50. Furthermore, it may suggest that less screening is required in the high-risk group beyond the age of 50.
|Date of Award||2020|
|Supervisor||Jonathan Berg (Supervisor) & Ellie Hothersall (Supervisor)|