title: Polymorphisms in WNT6 and WNT10A and colorectal adenoma risk.
abstract: 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.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Galbraith
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Poole
authors.forename: David
authors.initials: D
authors.lastname: Duggan
authors.forename: Jill
authors.initials: J
authors.lastname: Muehling
authors.forename: Li
authors.initials: L
authors.lastname: Hsu
authors.forename: Karen
authors.initials: K
authors.lastname: Makar
authors.forename: Liren
authors.initials: L
authors.lastname: Xiao
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Ulrich
mesh_terms: D000236:Adenoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D049109:Cell Proliferation; D003113:Colonoscopy / Q000379:methods; D015179:Colorectal Neoplasms / Q000235:genetics*; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D011795:Surveys and Questionnaires; D015854:Up-Regulation; D044465:White People; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D004041:Dietary Fats; C484142:WNT10A protein, human; C490674:WNT6 protein, human; D051153:Wnt Proteins; D051176:beta Catenin