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.