Document Detail


A molecular variant of the APC gene at codon 1822: its association with diet, lifestyle, and risk of colon cancer.
MedLine Citation:
PMID:  11221825     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The adenomatous polyposis coli (APC) gene is important in the etiology of colon cancer. Although germ-line mutations of this gene rarely occur in the population, less penetrant variants of the gene have been reported. One variant, producing an aspartate to valine change at codon 1822 (D1822V) [corrected] has been previously reported as having an allele frequency of 10%. The purpose of this study was to determine whether this D1822V [corrected] variant of the APC gene is associated with colon cancer and whether its association is influenced by other genetic or environmental factors. We used data collected as part of a multicenter study of 1,585 incident cases of colon cancer and 1,945 age- and sex-matched population-based controls to evaluate genetic, dietary, and environmental associations with the D1822V [corrected] variant of the APC gene. The frequency of the valine/valine allele at codon 1,822 was 22.8% in this population. In the control population, 61.5% were homozygote wild type, 33.3% were heterozygotes, and 5.2% were homozygote variant. Cases were slightly less likely to have the homozygous variant APC genotype than were controls [odds ratio (OR), 0.8; 95% confidence interval (CI), 0.6-1.1]; for those diagnosed after age 65, the homozygous APC variant was associated with reduced risk of colon cancer (OR, 0.6; 95% CI, 0.4-1.0). Assessment of the homozygous APC variant with dietary, genetic, and environmental factors showed that individuals with this genotype were at lower risk if they consumed a low-fat diet (OR, 0.2; 95% CI, 0.1-0.5) relative to those who were homozygous wild type and ate a high-fat diet. This finding was specific to a low-fat diet and was unrelated to other dietary variables. These results suggest that the codon 1,822 variant of the APC gene may have functional significance. Individuals who have the valine/valine variant of this gene may be at reduced risk of colon cancer if they eat a low-fat diet.
Authors:
M L Slattery; W Samowitz; L Ballard; D Schaffer; M Leppert; J D Potter
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  61     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-02-26     Completed Date:  2001-03-15     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1000-4     Citation Subset:  IM    
Affiliation:
Department of Family and Preventive Medicine University of Utah, Salt Lake City, 84112, USA.
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MeSH Terms
Descriptor/Qualifier:
Aged
Alleles
Case-Control Studies
Codon
Colonic Neoplasms / etiology,  genetics*
Diet*
Dietary Fats / adverse effects*
Female
Genes, APC
Genetic Predisposition to Disease
Humans
Life Style*
Male
Middle Aged
Risk Factors
Grant Support
ID/Acronym/Agency:
CA48998/CA/NCI NIH HHS; CA59045/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Codon; 0/Dietary Fats
Comments/Corrections
Erratum In:
Cancer Res 2001 Apr 1;61(7):3222

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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