Article

Lower Cancer Incidence in Amsterdam-I Criteria Families Without Mismatch Repair Deficiency: Familial Colorectal Cancer Type X

University of Toronto, Toronto, Ontario, Canada
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 05/2005; 293(16):1979-85. DOI: 10.1001/jama.293.16.1979
Source: PubMed

ABSTRACT

Approximately 60% of families that meet the Amsterdam-I criteria (AC-I) for hereditary nonpolyposis colorectal cancer (HNPCC) have a hereditary abnormality in a DNA mismatch repair (MMR) gene. Cancer incidence in AC-I families with MMR gene mutations is reported to be very high, but cancer incidence for individuals in AC-I families with no evidence of an MMR defect is unknown.
To determine if cancer risks in AC-I families with no apparent deficiency in DNA MMR are different from cancer risks in AC-I families with DNA MMR abnormalities.
Identification (1997-2001) of 161 AC-I pedigrees from multiple population- and clinic-based sources in North America and Germany, with families grouped into those with (group A) or without (group B) MMR deficiency by tumor testing. A total of 3422 relatives were included in the analyses.
Cancer incidence in groups A and B (excluding the 3 affected members used to define each pedigree as AC-I) and computed age- and sex-adjusted standardized incidence ratios (SIRs) using Surveillance, Epidemiology, and End Results data.
Group A families from both population- and clinic-based series showed increased incidence of the HNPCC-related cancers. Group B families showed increased incidence only for colorectal cancer (SIR, 2.3; 95% confidence interval, 1.7-3.0) and to a lesser extent than group A (SIR, 6.1; 95% confidence interval, 5.2-7.2) (P<.001).
Families who fulfill AC-I criteria but who have no evidence of a DNA MMR defect do not share the same cancer incidence as families with HNPCC-Lynch syndrome (ie, hereditary MMR deficiency). Relatives in such families have a lower incidence of colorectal cancer than those in families with HNPCC-Lynch syndrome, and incidence may not be increased for other cancers. These families should not be described or counseled as having HNPCC-Lynch syndrome. To facilitate distinguishing these entities, the designation of "familial colorectal cancer type X" is suggested to describe this type of familial aggregation of colorectal cancer.

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Available from: Kari G Chaffee
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    • "The following tumour characteristics were abstracted from the clinical histopathology report and/or from pathologist review: location, size, nodal status, differentiation, histologic type, and presence/absence of peritumoural lymphocytes, Crohn's-like reaction, tumour-infiltrating lymphocytes, and venous invasion. MSI and/or IHC were performed on all tumour samples (Lindor et al, 2005; Newcomb et al, 2007). Cases were allocated to one of the three groups: (1) 'LS' (n ¼ 312) for cases meeting AC1 and whose tumours were classified as MSI (MSI-high and/or MMR-deficient), (2) 'FCCTX' (n ¼ 177) for cases meeting AC1, but with non-MSI tumours, or (3) 'non-AC1' (n ¼ 12,175) for the remainder of CRC cases whose family histories did not meet AC1. "
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