Functional polymorphisms to modulate luminal lipid exposure and risk of colorectal cancer

Cancer Epidemiol. 2010 Jun;34(3):291-7. doi: 10.1016/j.canep.2010.02.010. Epub 2010 Mar 21.

Abstract

Purpose: Fat absorption may play a crucial role in colorectal carcinogenesis by determining intra-colonic exposure to potentially carcinogenic lipid metabolites.

Methods: We conducted a population-based case-control study that included 1163 cases and 1501 controls to examine whether individuals who carry genetic variants associated with lower lipid absorption have a higher risk of colorectal cancer. Using Taqman assay, we determined FABP2 alanine (A)/threonine (T) polymorphism at codon 54 in exon-2 and APOE isoforms. Multivariable odds ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional logistic regression models, assuming FABP2 A54 and APO non-E4 as high risk alleles.

Results: We found no associations with either of the polymorphisms. The OR associated with FABP2 A54 homozygotes compared with the others was 1.01 (95% CI; 0.86-1.45) and that for non-ApoE4 carriers compared with carries was 0.95 (95% CI; 0.80-1.13). However, there was a statistically significant negative interaction between total fat intake and FABP2 AA genotypes (p=0.025), indicating that the risk of colorectal cancer associated with this polymorphism is higher in the subjects with lower fat intake.

Conclusions: These results suggest that these SNPs may not be useful in predicting colorectal cancer risk in populations with high fat intake.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apolipoproteins E / genetics*
  • Apolipoproteins E / metabolism
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Disease Susceptibility
  • Fatty Acid-Binding Proteins / genetics*
  • Fatty Acid-Binding Proteins / metabolism
  • Female
  • Gene Frequency
  • Humans
  • Lipid Metabolism / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*

Substances

  • Apolipoproteins E
  • FABP2 protein, human
  • Fatty Acid-Binding Proteins