Polymorphisms in WNT6 and WNT10A and colorectal adenoma risk

Nutr Cancer. 2011;63(4):558-64. doi: 10.1080/01635581.2011.542539.


The WNT/β-catenin signaling pathway upregulates transcription of genes involved in cell proliferation and cancer progression; it has been implicated in colorectal adenoma formation. To date, no studies have examined polymorphisms in WNT genes or WNT gene-environment interactions in relation to adenoma risk. Within a colonoscopy-based case-control study of 628 adenoma cases and 516 polyp-free controls, we analyzed two tagSNPs in WNT6 (rs6747776 G > C, rs6754599 G > C) and WNT10A (rs7349332 G > A, rs10177996 A > G). The WNT6 rs6747776 homozygous minor allele (CC) was associated with increased risk of colorectal adenoma (OR = 2.75, 95% CI: 1.03-7.31). We observed a statistically significant interaction between WNT6 rs6747776 and the proportion of calories from total fat (P-int = 0.02), where the highest risk was observed among those with minor alleles and lowest fat intake. We also detected a marginally significant (0.05 < P ≤ 0.10) interaction with fish intake (P-int = 0.09). Additionally, a marginally significant interaction was observed between proportion of calories from saturated fat and the WNT10A rs7349332 polymorphism. Our results suggest that genetic variability in the WNT pathway may play a role in colorectal adenoma formation or may partly mediate the increased risk of colorectal cancer associated with fat intake.

Publication types

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

MeSH terms

  • Adenoma / genetics*
  • Adult
  • Aged
  • Alleles
  • Case-Control Studies
  • Cell Proliferation
  • Colonoscopy / methods
  • Colorectal Neoplasms / genetics*
  • Dietary Fats / administration & dosage
  • Female
  • Genotype
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Surveys and Questionnaires
  • Up-Regulation
  • White People
  • Wnt Proteins / genetics*
  • Wnt Proteins / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism


  • Dietary Fats
  • WNT10A protein, human
  • WNT6 protein, human
  • Wnt Proteins
  • beta Catenin