Clinicopathological Characteristics of Colorectal Cancer with Family History: an Evaluation of Family History as a Predictive Factor for Microsatellite Instability.
10.3346/jkms.2007.22.S.S91
- Author:
In Ja PARK
1
;
Hee Cheol KIM
;
Yong Sik YOON
;
Chang Sik YU
;
Se Jin JANG
;
Jin Cheon KIM
Author Information
1. Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea. jckim@amc.seoul.kr
- Publication Type:Original Article
- Keywords:
Familial Colorectal Cancer;
Family History;
Mutator Phenotype;
Ncrosatellite Instability
- MeSH:
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
- From:Journal of Korean Medical Science
2007;22(Suppl):S91-S97
- CountryRepublic of Korea
- Language:English
-
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.
