title: Do interleukin polymorphisms play a role in the prevention of colorectal adenoma recurrence by dietary flavonols?
abstract: Chemopreventive dietary compounds, such as flavonols, may inhibit colorectal carcinogenesis partly by altering cytokine expression and attenuating inflammation. Single nucleotide polymorphisms (SNPs) in the promoter regions of genes encoding cytokines may influence flavonol-induced changes in cytokine expression and consequently cancer risk. Using logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between SNPs of interleukin (IL)-1β, 6, 8, and 10 alone or combined with flavonol intake or serum IL concentration changes, and adenoma recurrence in 808 participants from the intervention arm of the Polyp Prevention Trial, a 4-year intervention study evaluating the effectiveness of a low-fat, high-fiber, high-fruit and vegetable diet on adenoma recurrence. Overall, SNPs in genes encoding IL-1β, 6, 8, and 10 were not associated with their corresponding serum concentrations or adenoma recurrence. However, individuals homozygous for IL-10 -592 C (OR=2.23, 95% CI: 1.07-4.66, P(interaction)=0.03) orIL-10 -819 C (OR=2.18, 95% CI: 1.05-4.51, P(interaction)=0.05) had an elevated risk of high-risk adenoma recurrence when their serum IL-10 concentrations increased during the trial. In addition, IL-6 -174 GG in combination with above median flavonol intake (OR=0.14, 95% CI: 0.03-0.66) or with decreased IL-6 concentrations (OR=0.14, 95% CI: 0.03-0.65) reduced the risk of advanced adenoma recurrence, although the interaction term was not statistically significant. In conclusion, our results suggest that IL SNPs, in combination with a flavonol-rich diet or decreased serum IL, may lower the risk of adenoma recurrence.
authors.affiliation: Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. gerd.bobe@oregonstate.edu
authors.forename: Gerd
authors.initials: G
authors.lastname: Bobe
authors.forename: Gwen
authors.initials: G
authors.lastname: Murphy
authors.forename: Paul S
authors.initials: PS
authors.lastname: Albert
authors.forename: Leah B
authors.initials: LB
authors.lastname: Sansbury
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Young
authors.forename: Elaine
authors.initials: E
authors.lastname: Lanza
authors.forename: Arthur
authors.initials: A
authors.lastname: Schatzkin
authors.forename: Nancy H
authors.initials: NH
authors.lastname: Colburn
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Cross
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D004032:Diet; D005260:Female; D044948:Flavonols / Q000627:therapeutic use*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D011379:Prognosis
chemical_list: D044948:Flavonols; D015850:Interleukin-6; D007378:Interleukins; D016753:Interleukin-10