The
peroxisome proliferator-activated receptor gamma (
PPARgamma) is one of a group of
ligand-activated
nuclear receptors responsible for regulation of
glucose,
lipid homeostasis, cell differentiation, and apoptosis. The 12
proline-to-
alanine (Pro12Ala) substitution polymorphism in
PPARgamma produces
proteins with lower activity. Variation in
PPARgamma expression in the bowel and the role of dietary
fatty acids as
ligands for
PPARgamma led investigation of whether the associations of diet with colon and
rectal cancer risk were modified by
PPARgamma genotype. Data (diet, lifestyle, and
DNA) came from case-control studies of colon (1,577 cases and 1,971 controls) and
rectal cancer (794 cases and 1,001 controls) conducted in Northern California, Utah, and the Twin City, Minnesota Metropolitan area (
colon cancer study only). Unconditional logistic regression models were adjusted for age at selection, body mass index, physical activity, energy intake,
dietary fiber, and
calcium. We found no significant interactions between macronutrient (fat,
protein, and
carbohydrate) and
colorectal cancer. High
lutein intake [odds ratio (OR), 0.63; 95% confidence interval (95% CI), 0.44-0.89], low refined grain intake (OR, 0.70; 95% CI, 0.53-0.94), or a high prudent diet score (OR, 0.66; 95% CI, 0.49-0.89) and PA/AA
PPARgamma genotype were associated with reduced
colon cancer risk. Risk of
rectal cancer was increased among those with the PA/AA
PPARgamma genotype and a high
mutagen index (OR, 1.63; 95% CI, 1.12, 2.36). Its unclear whether the alterations in risk in those with the less active phenotype for
PPARgamma is related to activation of
PPARgamma by nutrients or dietary patterns acting as
ligands or direct influences of these nutrients on colon and
rectal cancer processes that are important with lower
PPARgamma activity.