Multiple primary colorectal cancer: Individual or familial predisposition?

Abstract

Colorectal carcinoma (CRC) is one of the most frequent cancers. Along the surface of the large bowel, several foci of CRC may appear simultaneously or over the time. The development of at least two different tumours has been defined as multiple primary CRC (MPCRC): When more than one tumour is diagnosed at the same time, it is known as synchronous CRC (SCRC), while when a second neoplasm is diagnosed some time after the resection and/or diagnosis of the first lesion, it is called metachronous CRC (MCRC). Multiple issues can promote the development of MPCRC, ranging from different personal factors, such as environmental exposure, to familial predisposition due to hereditary factors. However, most studies do not distinguish this dichotomy. High- and low-pentrance genetic variants are involved in MPCRC. An increased risk for MPCRC has been described in Lynch syndrome, familial adenomatous polyposis, and serrated polyposis. Non-syndromic familial CRCs should also be considered as risk factors for MPCRC. Environmental factors can promote damage to colon mucosae that enable the concurrence of MPCRC. Epigenetics are thought to play a major role in the carcinogenesis of sporadic MPCRC. The methylation state of the DNA depends on multiple environmental factors (e.g., smoking and eating foods cooked at high temperatures), and this can contribute to increasing the MPCRC rate. Certain clinical features may also suggest individual predisposition for MPCRC. Different etiopathogenic factors are suspected to be involved in SCRC and MCRC, and different familial vs individual factors may be implicated. MCRC seems to follow a familial pattern, whereas individual factors are more important in SCRC. Further studies must be carried out to know the molecular basis of risks for MPCRC in order to modify, if necessary, its clinical management, especially from a preventive point of view.

Keywords: Multiple primary colorectal cancer; Synchronous colorectal cancer; Metachronous colorectal cancer; Chromosomal instability; Microsatellite instabillity; CpG island methylator phenotype

Core tip: Multiple primary colorectal cancer (MCRC), both Synchronous and Metachronous tumours, is not deeply studied yet, and also has a great clinical impact. Both genetic and environmental factors may affect in the development of MCRC, collaborating in promoting different foci of dysplasia. In general terms, Metachronous forms are mainly related to family factors whereas Synchronous tumours are linked with individual factors. With the exception of cases of hereditary forms of colorectal carcinoma (CRC), the others appears without a well-known molecular basis, and maybe different from sporadic colorectal cancer. For all these reasons, we present a review focused on the state of the art of these particular forms of CRC.