Ulcerative colitis and cancer

Abstract

Patients with ulcerative colitis (UC) are at an increased risk for the development of colorectal cancer (CRC). Unlike sporadic CRC, the cancer in UC patients arises from a focal or multifocal dysplastic mucosa in areas of inflammation. The clinical features of UC-associated cancer are similar to those found in patients with hereditary non-polyposis colorectal cancer. As with other varieties of CRC, UC-associated cancer exhibits a variety of genetic and molecular changes/abnormalities. These abnormalities are however clustered in areas of mucosae with histological abnormalities. The magnitude and timing of these changes are however significantly different. Surveillance and identification of patients at risk for cancer are a challenging problem.

Investigation of Genome Instability in Exfoliated Colonic Epithelial Cells and in Mitogen-Stimulated Lymphocytes of Patients with Ulcerative Colitis

“…UC-associated colorectal cancer occurs as a result of genetic and molecular abnormalities, such as alterations in tumor suppressor genes, oncogenes and genes encoding DNA repair proteins, as well as by an overall loss of genomic stability, similar to that seen in sporadic colorectal cancer [14,15,29,30]. Chromosomal instability is the most frequently occurring form of genomic instability in UC-associated cancers [29].…”

“…These results stronglysupport the theory that there is elevated genomic impairment in the lymphocytes of patients with UC. These spontaneous chromosome alterations are significantly associated with colon carcinoma rearrangements [14]. …”

“…The etiology of UC remains uncertain [14,15]. Despite a wide variety of causes, epidemiological studies have suggested that genetic susceptibility may provide a significant contribution to the etiology of this disease [16,17,18].…”

Gastric cancer following total proctocolectomy for colon cancer associated with ulcerative colitis

“…Known risk factors for cancer among patients with UC include younger age at diagnosis, greater extent and duration of UC, increased severity of inflammation, family history of colorectal cancer and coexisting primary sclerosing cholangitis [5][6][7]. Unlike sporadic colorectal cancer, UC-associated cancer exhibits a variety of genetic and molecular abnormalities even before any histological evidence of dysplasia or cancer [3,8]. While the background of these abnormalities is largely unknown, oxidative stress is suspected to be a significant factor in the activation of cancer-initiating genes like p53, DNA mismatch repair genes, and even DNA base excision-repair genes [3].…”

“…While the background of these abnormalities is largely unknown, oxidative stress is suspected to be a significant factor in the activation of cancer-initiating genes like p53, DNA mismatch repair genes, and even DNA base excision-repair genes [3]. To date, surveillance strategies for UC patients aim to screen for early signs of malignancy such as dysplasia or dysplasia-associated lesions [6,8,9]. As the colon cancer had developed in a patient with pancolitis, we suspected that the tumor was more likely to be associated with UC than to be sporadic.…”