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The "Amsterdam criteria" for the selection of families likely to have hereditary nonpolyposis colorectal cancer (HNPCC) have for some time been thought to be too restrictive (see Colorectal cancer summary for further information on the genetic basis of colorectal cancer). The International Collaborative Group on HNPCC have now suggested revised criteria ("Amsterdam criteria II") [Vasen, H.F. et al. (1999) Gastroenterology 116, 1453-1456]. These differ from the original criteria in that they include families with other strongly HNPCC-related cancers, even if colorectal cancer is not present. The new criteria are: There should be at least three relatives with an HNPCC-associated cancer (CRC, cancer of the endometrium, small bowel, ureter or renal pelvis); one should be a first degree relative of the other two; at least two successive generations should be affected; at least one should be diagnosed before the age of 50; familial adenomatous polyposis should be excluded in the CRC case(s), if any; tumours should be verified by pathological examination.

Comment: A useful feature of this paper is that it reiterates the original purpose of the Amsterdam criteria: "to provide a common nomenclature for the selection of families for studies and for the comparison of the results of these studies". The criteria were not intended to be used to select individuals or families to be offered genetic testing or various forms of cancer surveillance. Nor were they intended to constitute a definition of HNPCC. Genetic criteria (that is, mutations in mismatch repair genes, or microsatellite instability) have been excluded from both Amsterdam I and Amsterdam II. The reasons stated are that molecular analysis is not available to all families or in all countries, and so its inclusion would militate against the participation of many families in internationally-comparable studies. In addition, germ-line mismatch repair gene mutations are found in only a minority of families who satisfy the strictest family-history criteria for HNPCC, suggesting that other inherited mutations may remain to be identified [see Syngal, S. et al (1999) JAMA 282, 247-253 (Abstract) and O'Leary, T. (1999) JAMA 282, 281-282; also see item in June newsletter reporting similar results]. The International Collaborative Group on HNPCC stresses that the new Amsterdam criteria are not cast in stone, but may be modified as more information becomes available.