Characterization of Mutator Phenotype in Familial Colorectal Cancer Patients Not Fulfilling Amsterdam Criteria

Kim, Jin C.; Lee, Kang H.; Ka, In H.; Koo, Kum H.; Roh, Seon Ae; Kim, Hee C.; Yu, Chang Sik; Kim, Tae W.; Chang, Heung Moon; Gong, Gyung Yub; Kim, Jung S.

doi:10.1158/1078-0432.ccr-04-0651

Cited by 14 publications

(27 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Collectively, specific BER variants associated with AFAP mutations may play important roles in the tumorigenesis and growth of multiple adenomas. Histologically well-documented characteristics associated with p53 and MMR expression were found as in the other studies [16,35]. In our study, excluding the patients who underwent total colectomy, the mean adenoma/recurrence-free interval was significantly shorter in patients with ten or more adenomas than in those with fewer adenomas, indicating that patients with ten or more adenomas should be closely monitored.…”

Section: Discussionsupporting

confidence: 86%

MYH, OGG1, MTH1, and APC alterations involved in the colorectal tumorigenesis of Korean patients with multiple adenomas

Kim

Lee

et al. 2007

Virchows Arch

Self Cite

View full text Add to dashboard Cite

This study was done to characterize base excision repair (BER) genes and adenomatous polyposis coli (APC) alterations in the tumorigenesis of multiple colorectal adenomas in Korean patients. In total, 217 adenomas (mean number = 10) and 117 cancers were available from 143 patients. The heterozygous genotype of OGG1 c.1-18G>T was closely associated with multiple adenoma families (P < 0.001), while MYH A359V mutation exhibited a tendency (P = 0.053). MYH R170G mutation was exclusively identified in one patient. The G:C>T:A transversion or attenuated familial adenomatous polyposis (AFAP) mutations of APC was identified in the specific genotypes of BER variants. Tubular adenomas or adenomas with none-to-mild dysplasia were significantly associated with polymorphic genotypes of OGG1 IVS4-15 and S326C. In addition, large and pedunculated adenomas were more frequent in patients with G:C>T:A transversion and AFAP mutations of APC, respectively. However, BER variants were not associated with mismatch repair or altered p53 protein expression. Conclusively, two novel mutations of MYH and a novel OGG1 polymorphism seemed to be associated with multiple colorectal adenomas in Korean families, differing from those in other ethnic groups. Some BER variants involved in specific APC mutations are associated with characteristics of histogenesis other than altered mismatch repair or p53 pathway.

show abstract

Section: Discussionsupporting

confidence: 86%

MYH, OGG1, MTH1, and APC alterations involved in the colorectal tumorigenesis of Korean patients with multiple adenomas

Kim

Lee

et al. 2007

Virchows Arch

Self Cite

View full text Add to dashboard Cite

show abstract

“…Subjects with germline MMR gene mutations were not excluded from either study. However, such an increased risk has not been observed in all studies (26, 27). …”

Section: Discussionmentioning

confidence: 81%

Cancer Risks for the Relatives of Colorectal Cancer Cases with a Methylated MLH1 Promoter Region: Data from the Colorectal Cancer Family Registry

Levine

Win

Buchanan

et al. 2012

Cancer Prevention Research

View full text Add to dashboard Cite

Methylation of the MLH1 gene promoter region is an underlying cause of colorectal cancer (CRC) with high microsatellite instability (MSI-H) diagnosed in persons without a germline mutation in a mismatch repair (MMR) gene (non-Lynch Syndrome CRC). It is unclear whether relatives of CRC cases with MLH1 methylation have an increased risk of colorectal or other cancers. In this retrospective cohort study, we assessed risk of CRC and other cancers for the first- and second-degree relatives of CRC cases with a methylated MLH1 gene, by comparing observed numbers of cases with those expected based on age- sex- and country-specific cancer incidences (standardized incidence ratios – SIRs). The cohort consisted of 3128 first- and second-degree relatives of the 233 MLH1-methylated CRC cases with no MMR or MUTYH gene mutations. The SIR for CRC was 1.60 (95% confidence interval (95% CI) 1.22-2.16) for first-degree relatives (FDR) and 1.08 (0.74-1.60) for second-degree relatives (SDR). The SIR for gastric cancer was 2.58 (1.52-4.71) for FDR and 4.52 (2.23-10.61) for SDR and for ovarian cancer it was 2.16 (1.29-3.86) for FDR. The risk of liver cancer was also increased significantly in FDR but the estimate was based on only two cases. These data imply that relatives of CRC cases with MLH1 methylation may be at increased risk of CRC and stomach cancer and possibly ovarian and liver cancer, suggesting that there may be a heritable factor for CRC and other cancers associated with MLH1 methylation in non-Lynch Syndrome CRC’s.

show abstract

“…None of these patients was known to have germline mutations in hMLH1 and hMSH2 , indicative of HNPCC in the previous study (16). Family history was obtained from answers to a questionnaire and from an interview with a physician at the colorectal cancer clinic of Asan Medical Center.…”

Section: Methodsmentioning

confidence: 92%

“…In this study, we have focused on a subgroup of familial colorectal cancers; i.e., tumors from patients with first-degree relatives with colorectal cancers and no germline mutations in hMLH1 and hMSH2 (16). This group of cancers may be a mixture of heterogeneous tumors with different molecular profiles.…”

Section: Discussionmentioning

confidence: 99%

CpG Island Methylation in Familial Colorectal Cancer Patients Not Fulfilling the Amsterdam Criteria

et al. 2008

View full text Add to dashboard Cite

To determine the role of methylation in colorectal cancer patients with a family history, we enrolled 25 colorectal cancer patients with a family history of colorectal cancer but without a mutation in the hMLH1 and hMSH2 genes. Thirty patients with sporadic colorectal cancer were included as control. The methylation status of COX2, MGMT, hMLH1, TIMP3, p16, and MINT2 in normal mucosa and tumor were assessed using methylation-specific PCR. In patients with a family history, the methylation frequency ranged from 4.0% for TIMP3 to 44.4% for MGMT, whereas, in patients with sporadic colorectal cancer, it ranged from 6.7% for TIMP3 to 50.0% for p16. Nine of the 25 patients with family history (36.0%) were classified as methylation-prone, and nine of the 30 patients with sporadic cancers (30.0%) were as methylation-prone, making their methylation indices 0.19 and 0.16, respectively (p=0.522). As for the individual genes, the methylation rate of MGMT was higher in colorectal cancer patients with family history (44.0% vs. 13.0%, p=0.016), whereas the methylation rate of p16 was higher in sporadic colorectal cancers (50.0% vs. 8.7%, p=0.046). While CpG island methylation of tumor suppressor genes may play a role in colorectal carcinogenesis, the genes involved may be different between tumors of patients with and without a family history of colorectal cancer.

show abstract

Characterization of Mutator Phenotype in Familial Colorectal Cancer Patients Not Fulfilling Amsterdam Criteria

Cited by 14 publications

References 37 publications

MYH, OGG1, MTH1, and APC alterations involved in the colorectal tumorigenesis of Korean patients with multiple adenomas

MYH, OGG1, MTH1, and APC alterations involved in the colorectal tumorigenesis of Korean patients with multiple adenomas

Cancer Risks for the Relatives of Colorectal Cancer Cases with a Methylated MLH1 Promoter Region: Data from the Colorectal Cancer Family Registry

CpG Island Methylation in Familial Colorectal Cancer Patients Not Fulfilling the Amsterdam Criteria

Contact Info

Product

Resources

About