Table 1 Clinical criteria for identifying families with HNPCC

Amsterdam

Three relatives with colorectal cancer (CRC), one of whom is a first-degree relative of the other two; CRC involving at least two generations; one or more CRC cases diagnosed before the age of 50 years.

Modified Amsterdam

Very small families, which cannot be further expanded, can be considered as HNPCC even if only two CRCs in first-degree relatives; CRC must involve at least two generations, and one or more CRC cases must be diagnosed before the age of 55 years.

OR two first-degree relatives affected by CRC and the presence of a third relative with an unusual early onset neoplasm or endometrial cancer

Amsterdam II

Three relatives with an HNPCC-associated tumour (CRC, endometrial, small bowel, ureter or renal pelvis), one of whom is the first-degree relative of the other two; involving at least two generations; one or more cases diagnosed before the age of 50 years.

Bethesda

1 - Subjects with cancer in families that fulfil the Amsterdam criteria.

2 - Subjects with two HNPCC-related cancers, including synchronous and metachronous CRCs or associated extracolonic cancers.

3 - Subjects with CRC and a first-degree relative with CRC and/or HNPCC-related extracolonic cancers and/or colorectal adenoma(s); one of the cancers diagnosed at age <45 years and the adenoma(s) diagnosed at age <40 years.

4 - Subjects with CRC or endometrial cancer diagnosed at age <45 years.

5 - Subjects with right-sided CRC with an undifferentiated pattern (solid/cribriform) on histopathology diagnosed at age <45 years.

6 - Subjects with signet ring cell type CRC diagnosed at age <45 years.

7 - Subjects with colorectal adenoma(s) diagnosed at age <40 years.