J Korean Med Sci.  2007 Sep;22(Suppl):S91-S97. 10.3346/jkms.2007.22.S.S91.

Clinicopathological Characteristics of Colorectal Cancer with Family History: an Evaluation of Family History as a Predictive Factor for Microsatellite Instability

• Park IJ
• Kim HC
• Yoon YS
• Yu CS
• Jang SJ
• Kim JC

• KMID: 1785795
• DOI: http://doi.org/10.3346/jkms.2007.22.S.S91

Abstract

To determine whether family history of cancer may be a risk factor for the mutator phenotype in colorectal cancer, we recruited 143 consecutive colorectal cancer patients with a family history of accompanying cancers not meeting the Amsterdam criteria. Microsatellite instability (MSI) at 5 markers, hMLH1-promoter methylation, and expression of mismatch repair (MMR) proteins (hMLH1, hMSH2, hMSH6, hMPS1, and hPMS2) were determined. Among the relatives of familial colorectal cancer patients, colorectal cancer was the most common tumor type. Of the proband colorectal cancers, 26 (18.2%) showed high-level MSI (MSI-H); 47 additional tumors with mutator phenotype (32.9%) were identified by hMLH1-promoter methylation and/or loss of MMR protein expression. Mutator phenotype was associated with right-sided colon cancer and the type of accompanying cancer. Family history, which was differentially quantified according to the degree of relatives and the type of accompanying cancers, effectively discriminated MSI-H from microsatellite stable (MSS) and low-level microsatellite instability (MSI-L) and mutator phenotypes. Our findings indicate that familial colorectal cancer may be associated with multiple occurrences of colorectal or accompanying cancers and that family history could be correlated with microsatellite instability.

Keyword

Familial Colorectal Cancer; Family History; Mutator Phenotype; Ncrosatellite Instability

MeSH Terms

Adaptor Proteins, Signal Transducing/genetics/metabolism
Adenosine Triphosphatases/metabolism
Adult
Aged
Aged, 80 and over
Base Sequence
Colorectal Neoplasms/*genetics/metabolism/pathology
DNA Methylation
DNA Mismatch Repair
DNA Repair Enzymes/metabolism
DNA, Neoplasm/genetics
DNA-Binding Proteins/metabolism
Female
Humans
Male
*Microsatellite Instability
Middle Aged
MutS Homolog 2 Protein/metabolism
Neoplasm Proteins/metabolism
Nuclear Proteins/genetics/metabolism
Phenotype
Promoter Regions, Genetic
Risk Factors

Figure

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  Fig. 1 Association between the familial impact value (FIV), a quantification of family history according to the type of cancer and the relationship of the affected relatives, and MSI status on receiver operating characteristic (ROC) curves. FIVt, all accompanying cancers; FIVc, colorectal and HNPCC-associated cancers.

• 

  Fig. 2 Association between the familial impact value (FIV) and mutator phenotype on receiver operating characteristic (ROC) curves. FIVt, all accompanying cancers; FIVc, colorectal and HNPCC-associated cancers.

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