Extracolonic cancer risk in Dutch patients with APC (adenomatous polyposis coli)-associated polyposis.

BACKGROUND: Screening of patients with familial adenomatous polyposis (FAP) have led to a substantial reduction in mortality due to colorectal cancer (CRC). Recent guidelines suggest that surveillance of non-intestinal malignancies should also be considered in those patients. However, the value of these surveillance programmes is unknown. The aims of this study were (1) to assess the occurrence of extracolonic malignancies in a large series of adenomatous polyposis coli (APC) mutation carriers and (2) to evaluate the causes of death. METHODS: All APC mutation carriers were selected from the Dutch polyposis registry. Data on causes of death were collected. Pathology reports were retrieved from the Dutch Pathology Registry. RESULTS: A total of 85 extracolonic malignancies were diagnosed in 74 of 582 APC mutation carriers. Duodenal and skin cancers were the most prevalent cancers. Thyroid cancer was observed in only 1.5% of the cases. The main cause of death was cancer (59% of all deaths), with 42% due to CRC and 21% due to duodenal cancer. One patient died from thyroid cancer. The second and third most common causes of death were cardiovascular disease (13% of all deaths) and desmoid tumours (11% of all deaths), respectively. CONCLUSION: Extending surveillance programmes to other cancers will not contribute significantly to the survival of patients with FAP.

Features of incident colorectal cancer in Lynch syndrome.

BACKGROUND AND OBJECTIVE: Despite intensive colonoscopic surveillance, a substantial proportion of Lynch syndrome (LS) patients develop colorectal cancer (CRC). The aim of this study was to characterize incident CRC in LS patients. METHODS: All patients diagnosed with incident CRC after start of colonoscopic surveillance were identified in the Dutch LS Registry of 905 patients. A retrospective analysis of patient records was carried out for patient characteristics, survival, CRC characteristics and findings of previous colonoscopy. RESULTS: Seventy-one patients (7.8%) were diagnosed with incident CRC. Median interval between incident CRC diagnosis and previous colonoscopy was 23.8 (range 6.7-45.6) months. Median tumor diameter was 2.5 cm, and 17% of the tumors were sessile or flat. Most patients (83%) had no lymph node metastases. There was no association between tumor size and colonoscopy interval or lymph node status. Most patients (65%) had no adenomas during previous colonoscopy. Two patients (2.8%) eventually died from metastatic CRC. CONCLUSION: The high frequency of incident CRC in LS likely results from several factors. Our findings lend support to the hypothesis of fast conversion of adenomas to CRC, as 65% of patients had no report of polyps during previous colonoscopy. High-quality colonoscopies are essential, especially as tumors and adenomas are difficult to detect because of their frequent non-polypoid appearance. Early detection due to surveillance as well as the indolent growth of CRC, as demonstrated by the lack of lymph node metastases, contributes to the excellent survival observed.

Single-nucleotide polymorphisms of matrix metalloproteinases and their inhibitors in gastrointestinal cancer.

Matrix metalloproteinases (MMPs) are implicated in cancer development and progression and are associated with prognosis. Single-nucleotide polymorphisms (SNPs) of MMPs, most frequently located in the promoter region of the genes, have been shown to influence cancer susceptibility and/or progression. SNPs of MMP-1, -2, -3, -7, -8, -9, -12, -13 and -21 and of the tissue inhibitor of metalloproteinases (TIMPs) TIMP-1 and TIMP-2 have been studied in digestive tract tumors. The contribution of these polymorphisms to the cancer risk and prognosis of gastrointestinal tumors are reviewed in this paper.