Interaction between oxidative stress-related exposures and genes that encode antioxidant enzymes in a case-control study of colorectal adenoma Open Access

Labadie, Julia Denise (2012)

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Previous research found inverse associations between oxidative balance and risk of colorectal
adenoma. However, all previous measures of oxidative balance were limited to extrinsic
(lifestyle and dietary) factors and did not include intrinsic factors, specifically antioxidant
enzymes responsible for cellular defense against oxidative stress. Using data pooled from three
colonoscopy-based case-control studies of incident, sporadic colorectal adenoma (n=1,050) that
collected information on participants' medical history, usual dietary intakes, and lifestyle, we
considered 11 extrinsic factors with known pro- or anti-oxidant properties. Using these factors,
we constructed an oxidative balance score (OBS) in which points were awarded for each pro-
and antioxidant exposure so that higher OBS values represented a higher balance of antioxidants
to pro-oxidants. We used multivariate logistic regression to assess whether the association
between OBS and colorectal adenoma differed according to polymorphisms in genes encoding
antioxidant enzymes. For participants in the highest compared to those in the lowest OBS
category, the odds ratio (OR) for the OBS-adenoma association was 0.51 (95% confidence
interval [CI] 0.32 - 0.82). For 11 catalase ( CAT) single nucleotide polymorphisms (SNPs), the
OBS-adenoma inverse association was stronger for participants homozygous for the most
common allele for two of the SNPs and for those with one or more variant alleles in three, with
the strongest being for those homozygous for the rs499406 variant A allele (OR 0.27; CI 0.08 -
0.92). For six manganese superoxide dismutase ( MnSOD) SNPs, the inverse association was
stronger for participants with at least one variant allele in three of the SNPs, with the strongest
being for the rs5746151 variant A allele (OR 0.11; CI 0.02 - 0.77). For five gluthathione-S-
transferase P1 ( GSTP1) SNPs, the inverse association was stronger for participants homozygous
for the most common allele in one SNP, and for those homozygous for the variant allele in
another, with the strongest being for those homozygous for the rs4147581 variant G allele (OR
0.24; CI 0.09 - 0.67). These findings provide limited support for the hypothesis that variation in
antioxidant enzyme genes may modify associations of environmental exposures related to
oxidative balance and risk for sporadic colorectal adenoma.

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