Clinical and Molecular Comparative Study of Colorectal Cancer Based on Age-of-onset and Tumor Location
In Europe, colorectal cancer (CRC) is the third most common cancer in males, the second most common cancer in females, and the fourth most common cause of cancer-related deaths; worldwide, 1,360,000 new cases are diagnosed each year and it causes 700,000 deaths . Biologically, it represents a heterogeneous disease. Early-onset colorectal cancer (EOCRC) represents 11% of colon cancers and 18% of rectal cancers, and its incidence is increasing . Several studies have described different genetics, biological and clinical behavior in this age group, suggesting that it may be a specific subgroup within CRC, and that age-of-onset should be a major criterion for its subclassification [3,4]. Moreover, new findings may also define some particular subtypes, such as rectal cancer with microsatellite-stability (MSS) and without chromosomal instability (CIN-) .
The predisposition of the three main carcinogenetic CRC pathways to different locations in the colon, together with studies demonstrating that right and left-sided CRCs exhibit different genetic, biological and demographical characteristics and risk factors, suggest that the carcinogenetic mechanism and progression of CRC may differ with tumor location. Thus, the anatomic site of origin of CRC appears to be another good discriminator for the subclassification of this type of neoplasm
[6–8]. Along these lines, we recently analyzed tumor location (right colon, left colon and rectum) as a discriminatory factor within EOCRC and clinical differences emerged as well as the different main carcinogenetic pathways predominant within each location .
For the past few years, while characterizing EOCRC from different points of view, we have been comparing series of features with their correlates in late-onset CRC (LOCRC) in order to assess whether they have a different molecular basis [3,4,10]. Therefore, our purpose at this point is to confirm whether our previous findings that the differential clinical and molecular features of tumors with a different location in CRC and the age-of-onset as a major criterion to classify CRC, hold up together. If so, right colon, left colon and rectal cancers should be substantially different between early and late age-of-onset groups.