3'-UTR and functional secretor haplotypes in mannose-binding lectin 2 are associated with increased colon cancer risk in African Americans

Cancer Res. 2012 Mar 15;72(6):1467-77. doi: 10.1158/0008-5472.CAN-11-3073. Epub 2012 Jan 26.

Abstract

Because chronic intestinal inflammation is a risk factor for colorectal cancer, we hypothesized that genetic variants of inflammatory mediators, such as mannose-binding lectin 2 (MBL2), are associated with colon cancer susceptibility. Here, we report the association of 24 MBL2 single-nucleotide polymorphisms (SNP) and corresponding haplotypes with colon cancer risk in a case-control study. Four SNPs in the 3'-untranslated region (UTR) of the gene (rs10082466, rs2120132, rs2099902, and rs10450310) were associated with an increased risk of colon cancer in African Americans. ORs for homozygous variants versus wild-type ranged from 3.17 [95% confidence interval (CI), 1.57-6.40] to 4.51 (95% CI, 1.94-10.50), whereas the 3'-UTR region haplotype consisting of these four variants had an OR of 2.10 (95% CI, 1.42-3.12). The C allele of rs10082466 exhibited a binding affinity of miR-27a and this allele was associated with both lower MBL plasma levels and activity. We found that 5' secretor haplotypes known to correlate with moderate and low MBL serum levels exhibited associations with increased risk of colon cancer in African Americans, specifically as driven by two haplotypes, LYPA and LYQC, relative to the referent HYPA haplotype (LYPA: OR, 2.60; 95% CI, 1.33-5.08 and LYQC: OR, 2.28; 95% CI, 1.20-4.30). Similar associations were not observed in Caucasians. Together, our results support the hypothesis that genetic variations in MBL2 increase colon cancer susceptibility in African Americans.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adult
  • Aged
  • Black People / genetics*
  • Black People / statistics & numerical data
  • Black or African American
  • Case-Control Studies
  • Colonic Neoplasms / epidemiology
  • Colonic Neoplasms / genetics*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Haplotypes*
  • Humans
  • Male
  • Mannose-Binding Lectin / blood
  • Mannose-Binding Lectin / genetics*
  • Middle Aged
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide
  • Risk
  • White People / genetics
  • White People / statistics & numerical data

Substances

  • 3' Untranslated Regions
  • MBL2 protein, human
  • Mannose-Binding Lectin