Document Detail

Low-penetrance genes and their involvement in colorectal cancer susceptibility.
MedLine Citation:
PMID:  12433710     Owner:  NLM     Status:  MEDLINE    
This report focuses on low-penetrance genes that are associated with colorectal adenoma and/or cancer or that are in strong linkage disequilibrium with colorectal adenoma and/or cancer causing variants. A pooled analysis was performed for 30 polymorphisms in 20 different genes that have been reported in more than one colorectal adenoma or cancer study. An association with colorectal cancer was found for seven polymorphisms in seven genes reported in more than one study; no associations were found with colorectal adenoma. Four of the polymorphisms exhibited an increased colorectal cancer risk [GSTT1, NAT2 (phenotype), HRAS1, and ALDH2]. Two others [MTHFR, Tp53 (intron 3)] exhibited a decreased risk. For the tumor necrosis factor (TNF)a polymorphism of the TNF-alpha gene, one allele was associated with an increased risk (a2 allele) and two other TNFa alleles with decreased risks (a5 and a13 allele). No association with colorectal adenoma and/or cancer was detected for 23 other polymorphisms in 15 genes. However, of all 30 polymorphisms, only three pooled analyses had sufficiently large samples to confirm (MTHFR) or to exclude (GSTM1 and NAT2 genotype) the association with a P < 0.0026 and a power of 90%. Eighteen polymorphisms in 15 genes were each described in only one study, all with very small sample sizes. For 11 polymorphisms in 10 of these genes, an association with colorectal adenoma and/or cancer was found. Only simultaneous genotyping and combined analysis of different polymorphisms in large numbers of patients and controls, stratified by ethnicity, gender, and tumor localization and taking relevant dietary and lifestyle habits into account, will make it possible to describe the exact relations between polymorphisms and colorectal cancer susceptibility with an adequate power.
Mirjam M de Jong; Ilja M Nolte; Gerard J te Meerman; Winette T A van der Graaf; Elisabeth G E de Vries; Rolf H Sijmons; Robert M W Hofstra; Jan H Kleibeuker
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology     Volume:  11     ISSN:  1055-9965     ISO Abbreviation:  Cancer Epidemiol. Biomarkers Prev.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-11-15     Completed Date:  2003-03-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9200608     Medline TA:  Cancer Epidemiol Biomarkers Prev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1332-52     Citation Subset:  IM    
Department of Gastroenterology, University Hospital Groningen, The Netherlands.
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MeSH Terms
Adenoma / enzymology,  genetics*
Colorectal Neoplasms / enzymology,  genetics*
Genetic Predisposition to Disease / genetics
Polymorphism, Genetic / genetics

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

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