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- CRC, colorectal cancer
- HNPCC, hereditary non-polyposis colorectal cancer
- MSI, microsatellite instability
- ECC, extracolonic cancer
A positive family history has been shown to be an important risk factor for colorectal cancer (CRC). Part of the familial aggregation is explained by the inherited diseases familial adenomatous polyposis and hereditary non-polyposis colorectal cancer (HNPCC).1 The latter syndrome is characterised by a high risk of colorectal cancer with a high rate of multiple primary tumours and a young age of onset, and also by a high risk of cancers of other organs (endometrium, stomach, pancreas, ovary, small intestine, urinary tract).2 The germline mutations which cause this syndrome have been shown to occur on genes that are responsible for repairing DNA mismatches. In humans, six mismatch repair (MMR) genes have been identified (hMLH1, hMSH2, hPMS1, hPMS2, hMSH6, and hMSH3) but germline mutations have been found in the first five only, mostly in hMLH1 and hMSH2.3 It is now commonly accepted that the lifetime risk of colorectal cancer in MMR carriers is very high, between 70% and 90%. A recent review of the available data indicated a lifetime risk of colorectal cancer of 74% or more in males, a somewhat lower risk in females, and a lifetime endometrial cancer risk of 42% or more in female mutation carriers.4
Apart from the preferential localisation of tumours in the proximal part of the colon, and the high frequency of multiple tumours, there is no specific individual characteristic of the syndrome. Therefore, the syndrome is diagnosed in patients on familial criteria. The classical criteria are the so-called “Amsterdam criteria”,5 which were issued in an effort to standardise clinical studies and to ensure that only families with HNPCC would be classified as such. These very stringent criteria include: (1) three relatives with colon cancer, two of them being first degree relatives of the third; …
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