V. Lemmens

INTRODUCTION: Hyperplastic polyposis syndrome (HPS) is characterised by the presence of multiple colorectal hyperplastic polyps and is associated with an increased colorectal cancer (CRC) risk. For first-degree relatives of HPS patients (FDRs) this has not been adequately quantified. Reliable evidence concerning the magnitude of a possible excess risk is necessary to determine whether preventive measures, like screening colonoscopies, in FDRs are justified. AIMS AND METHODS: We analysed the incidence rate of CRC in FDRs and compared this with the general population through person-year analysis after adjustment for demographic characteristics. Population-based incidence data from the Eindhoven Cancer Registry during the period 1970-2006 were used to compare observed numbers of CRC cases in FDRs with expected numbers based on the incidence in the general population. RESULTS: A total of 347 FDRs (41% male) from 57 pedigrees were included, contributing 11 053 person-years of follow-up. During the study period, a total of 27 CRC cases occurred among FDRs compared to five expected CRC cases (p<0.001). The RR of CRC in FDRs compared to the general population was 5.4 (95% CI 3.7 to 7.8). Four FDRs satisfied the criteria for HPS. Based on the estimated HPS prevalence of 1:3000 in the general population the projected RR of HPS in FDRs was 39 (95% CI 13 to 121). CONCLUSIONS: FDRs of HPS patients have an increased risk for both CRC and HPS compared to the general population. Hence, as long as no genetic substrate has been identified, screening colonoscopies for FDRs seem justified but this needs to be prospectively evaluated.

Background Colorectal cancer (CRC) is a heterogeneous disease: cancers in proximal, distal colon and rectum show differences in carcinogenesis pathways (proximal colon cancer related to microsatellite instability vs distal colon cancer to allelic losses), epidemiological patterns and clinical characteristics. By assessing the risk of second primary CRC among CRC patients, we aimed to shed light on the aetiology of multiple CRCs and its clinical relevance. Material and Methods We analysed the risk of second CRC among 123 253 first CRC patients from the Netherlands Cancer Registry data. Standardised incidence ratio (SIR) was computed to compare risk of second CRC among CRC patients with the general population. Results During a median follow-up of 2 years, 2720 second CRC were diagnosed in CRC patients. More than 50% of second CRC were located in the proximal colon translating into a fourfold RR when compared with general population (SIR=4.1, 95% CI 3.9 to 4.3). Although we did not observe specific high risk pairs between sub sites of the first and second CRC, interestingly, right-side predomination of second CRC risk was clear. The right-side shifting of second CRC persists even after 10 years of follow-up in all patients' sub-groups that is, synchronous and metachronous cancers, by follow-up time and sub-sites of first CRC. Discussion and Conclusion Our results highlighted the crucial role of microsatellite instability in the development second CRC. Due to the persistently elevated risk of a proximal colon cancer, surveillance on this specific site is recommended, preferably using FOBT.