Colorectal cancer is cancer that develops in the tissues of the colon or rectum. Your colon and rectum are part of your digestive system:
- Your colon is the first and longest part of your large intestine. It absorbs water and some nutrients from foods. It also changes the leftover waste products into stool (poop).
- Your rectum is the lower part of your large intestine. It’s where your body stores stool.
Cancer that begins in the colon is called colon cancer, and cancer that begins in the rectum is called rectal cancer. Cancer that affects either of these parts may also be called colorectal cancer.
Epidemiology
CRC affects approximately 135,439 estimated new patients with a corresponding 95,520 (70%) due to Cca in the United States every year. Among all cancers sites, it is the second leading cause of death in the United States, with an estimated 50,260 deaths, when colon and rectum are combined. The CRC incidence rate has been declining 3% per year since 2004 although increasing by 2% per year among screened young adults (younger than 50 years). [9][10][11]The prior reflects an uptake on screening patterns and removal of precancerous lesions. CRC incidence varies worldwide with higher rates in developed countries than in unindustrialized countries. Low socioeconomic status has an increased risk of CRC associated with poor risk behavior and access to medical care. White American lifetime average incidence of CRC is 5% but is higher in men (greater than 20%) than in woman and African Americans (greater than 25%) than non-Hispanic whites. Findings from epidemiologic studies indicate a gradual anatomic distribution of Cca, shifting from the left-distal colon toward the right sided or proximal end, once more related to more effective left-sided screening modalities. From 1975 to 2014, there has been a 51% decrease in the mortality of CRC in the United States, attributed to early detection and improvement of treatment modalities. National Cancer Institute estimates that 65% of all treated patients for Cca will be alive at the 5-year mark.
The transformation of the normal colonic epithelium to a precancerous lesion (adenoma) and ultimately to invasive carcinoma requires an accumulation of genetic mutations either somatic (acquired) and/or germline (inherited). The theory of colonic carcinogenesis features a clonal mutation evolution that gives a cell survival-immortality advantage and allows to develop more mutations providing other cancer hallmarks as proliferation, invasion, metastasis, and others.[12][13] Clinical evidence has shown that CRCs frequently arise from adenomatous polyps that typically acquire dysplastic changes in a 10 to 15-year period before developing invasive carcinoma, and the early detection-removal of polyps will reduce the incidence of CRC. New evidence has exposed that hamartomatous and serrated polyps could lead to CRC. There are three major molecular pathways linked to CRC, chromosomal instability, mismatch repair, and hypermethylation. The chromosomal instability pathway is a gain of mutations unbalancing oncogene and tumor suppressors equilibrium as seen with mutations in the adenomatous polyposis coli (APC), a hallmark of FAP. Cells with deficiency of DNA mismatch repair (dMMR), commonly MLH1 or MSH2, accumulate errors within the genome that further will be repeated causing high levels of microsatellite instability (MSI-H), a hallmark of Lynch syndrome. CpG hypermethylation of DNA could activate or silence the expression of certain genes, BRAF and MLH1 respectively. Sporadic oncogenes somatic mutations (RAS, SRC, MYC) have been implicated in CRC, being RAS the most clinical relevance. RAS mutations variants (HRAS, KRAS, NRAS) are found in 50% of CRC sporadic cases, currently being exploited on CRC screening by stool-DNA testing, the absence of epidermal growth factor receptors (EGFR) targeted therapy response and potential direct targeted agents. In the other hand, tumor suppressors genes require bi-allelic loss (“two-hit model”) and are described in loss of APC 5q21 gene (80% sporadic), TP53 17p gene (50-70% sporadic), and DCC/SMAD2-4 18q gene (73% sporadic). Specific MMR gene mutations could occur in hMSH2, hMLH1, hPMS1 and hPMS2, hMSH6, and hMLH3; each one of them that interact with MLH1 and approximately found in 15% of all sporadic CRC causing a Lynch-like syndrome with MSI-H calling for universal testing. MUTYH defects have a recessive inheritance pattern at a time requiring bi-allelic second hit or in conjunction with APC gene mutation. Cyclooxygenase (COX-2) and peroxisome proliferator–activating receptor (PPAR) genes have been implicated in CRC tumorigenesis currently under investigation for chemo-protection.
What are the signs and symptoms of colon cancer?
Colon cancer often does not cause symptoms in the early stages. That’s why we recommend that you get regular screenings for colon cancer depending on your age, medical history, and other risk factors.
However, there are some signs of colon cancer that you should not ignore, such as:
- rectal bleeding or blood in your stool
- changes in your bowel habits, such as diarrhea, constipation, or narrow stools that last more than a few days
- unexplained abdominal pain or cramping that lasts more than a few days
- a persistent urge for a bowel movement that doesn’t go away after you have one
- unexplained weakness and fatigue
- unintended weight loss
- a diagnosis of anemia
