Document Detail


Genetic polymorphisms in fatty acid metabolism genes and colorectal cancer.
MedLine Citation:
PMID:  22294764     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Epidemiological risk factors for CRC included dietary fat intake; consequently, the role of genes in the fatty acid biosynthesis and metabolism pathways is of particular interest. Moreover, hyperlipidaemia has been associated with different type of cancer and serum lipid levels could be affected by genetic factors, including polymorphisms in the lipid metabolism pathway. The aim of this study is to assess the association between single-nucleotide polymorphisms (SNPs) in fatty acid metabolism genes, serum lipid levels, body mass index (BMI) and dietary fat intake and CRC risk; 30 SNPs from 8 candidate genes included in fatty acid biosynthesis and metabolism pathways were genotyped in 1780 CRC cases and 1864 matched controls from the Molecular Epidemiology of Colorectal Cancer study. Information on clinicopathological characteristics, lifestyle and dietary habits were also obtained. Logistic regression and association analysis were conducted. Several LIPC (lipase, hepatic) polymorphisms were found to be associated with CRC risk, although no particular haplotype was related to CRC. The SNP rs12299484 showed an association with CRC risk after Bonferroni correction. We replicate the association between the T allele of the LIPC SNP rs1800588 and higher serum high-density lipoprotein levels. Weak associations between selected polymorphism in the LIPC and PPARG genes and BMI were observed. A path analysis based on structural equation modelling showed a direct effect of LIPC gene polymorphisms on colorectal carcinogenesis as well as an indirect effect mediated through serum lipid levels. Genetic polymorphisms in the hepatic lipase gene have a potential role in colorectal carcinogenesis, perhaps though the regulation of serum lipid levels.
Authors:
M Crous-Bou; G Rennert; R Salazar; F Rodriguez-Moranta; H S Rennert; F Lejbkowicz; L Kopelovich; S M Lipkin; S B Gruber; V Moreno
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Mutagenesis     Volume:  27     ISSN:  1464-3804     ISO Abbreviation:  Mutagenesis     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-02-01     Completed Date:  2012-05-17     Revised Date:  2013-05-20    
Medline Journal Info:
Nlm Unique ID:  8707812     Medline TA:  Mutagenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  169-76     Citation Subset:  IM    
Affiliation:
Colorectal Cancer Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona 08907, Spain.
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MeSH Terms
Descriptor/Qualifier:
Aged
Body Mass Index
Case-Control Studies
Colorectal Neoplasms / epidemiology,  genetics*
Fatty Acids / genetics*,  metabolism*
Female
Genetic Predisposition to Disease*
Haplotypes
Humans
Israel / epidemiology
Lipase / genetics*
Male
Neoplasm Proteins / genetics*
Polymorphism, Single Nucleotide / genetics*
Risk Factors
Grant Support
ID/Acronym/Agency:
5 P30 CA46592/CA/NCI NIH HHS; N01-CN43308/CN/NCI NIH HHS; NCI R01-CA81488/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/Neoplasm Proteins; EC 3.1.1.3/Lipase
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