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DNMT3b polymorphism and hereditary nonpolyposis colorectal cancer age of onset.

Publication ,  Journal Article
Jones, JS; Amos, CI; Pande, M; Gu, X; Chen, J; Campos, IM; Wei, Q; Rodriguez-Bigas, M; Lynch, PM; Frazier, ML
Published in: Cancer Epidemiol Biomarkers Prev
May 2006

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome of familial malignancies resulting from germ-line mutations in DNA mismatch repair genes. Colorectal and endometrial cancers are most frequently observed. A polymorphic C-to-T change in the promoter region of the DNMT3b gene, -149 bp from the transcription start site, is reported to greatly increase promoter activity and is associated with increased risk for lung cancer and decreased postsurgical survival in patients with small cell carcinoma of the head and neck. We studied the influence of this DNMT3b polymorphism on HNPCC age of onset. We determined the DNMT3b genotype of 146 mismatch repair mutation carriers from 72 families. Of these, 74 participants had colorectal cancer. The participants were genotyped by single-strand conformational polymorphism analysis and DNA sequencing. We tested the association between age of onset and DNMT3b genotypes by comparing Kaplan-Meier survival curves, evaluating the homogeneity of the curves using the log-rank test, Wilcoxon's test, and Fleming-Harrington test and estimating the strength and direction of the association using the Cox proportional hazards regression model adjusting for potential demographic and genetic confounding factors. HNPCC patients carrying one or two copies of the DNMT3b variant T allele developed their colorectal cancer significantly earlier than HNPCC patients who were homozygous for the wild-type DNMT3b allele. Combining knowledge of an individual's DNMT3b genotype with information on other genetic and environmental risk factors may improve risk estimates and help to identify individuals who are genetically susceptible to developing HNPCC at an earlier age.

Duke Scholars

Published In

Cancer Epidemiol Biomarkers Prev

DOI

ISSN

1055-9965

Publication Date

May 2006

Volume

15

Issue

5

Start / End Page

886 / 891

Location

United States

Related Subject Headings

  • Survival Analysis
  • Statistics, Nonparametric
  • Sequence Analysis, DNA
  • Risk Factors
  • Proportional Hazards Models
  • Promoter Regions, Genetic
  • Polymorphism, Single-Stranded Conformational
  • Polymorphism, Genetic
  • Polymerase Chain Reaction
  • Mutation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Jones, J. S., Amos, C. I., Pande, M., Gu, X., Chen, J., Campos, I. M., … Frazier, M. L. (2006). DNMT3b polymorphism and hereditary nonpolyposis colorectal cancer age of onset. Cancer Epidemiol Biomarkers Prev, 15(5), 886–891. https://doi.org/10.1158/1055-9965.EPI-05-0644
Jones, J Shawn, Christopher I. Amos, Mala Pande, Xiangjun Gu, Jinyun Chen, Imelda M. Campos, Qingyi Wei, Miguel Rodriguez-Bigas, Patrick M. Lynch, and Marsha L. Frazier. “DNMT3b polymorphism and hereditary nonpolyposis colorectal cancer age of onset.Cancer Epidemiol Biomarkers Prev 15, no. 5 (May 2006): 886–91. https://doi.org/10.1158/1055-9965.EPI-05-0644.
Jones JS, Amos CI, Pande M, Gu X, Chen J, Campos IM, et al. DNMT3b polymorphism and hereditary nonpolyposis colorectal cancer age of onset. Cancer Epidemiol Biomarkers Prev. 2006 May;15(5):886–91.
Jones, J. Shawn, et al. “DNMT3b polymorphism and hereditary nonpolyposis colorectal cancer age of onset.Cancer Epidemiol Biomarkers Prev, vol. 15, no. 5, May 2006, pp. 886–91. Pubmed, doi:10.1158/1055-9965.EPI-05-0644.
Jones JS, Amos CI, Pande M, Gu X, Chen J, Campos IM, Wei Q, Rodriguez-Bigas M, Lynch PM, Frazier ML. DNMT3b polymorphism and hereditary nonpolyposis colorectal cancer age of onset. Cancer Epidemiol Biomarkers Prev. 2006 May;15(5):886–891.

Published In

Cancer Epidemiol Biomarkers Prev

DOI

ISSN

1055-9965

Publication Date

May 2006

Volume

15

Issue

5

Start / End Page

886 / 891

Location

United States

Related Subject Headings

  • Survival Analysis
  • Statistics, Nonparametric
  • Sequence Analysis, DNA
  • Risk Factors
  • Proportional Hazards Models
  • Promoter Regions, Genetic
  • Polymorphism, Single-Stranded Conformational
  • Polymorphism, Genetic
  • Polymerase Chain Reaction
  • Mutation