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Genetic variation in PPARGC1A may affect the role of diet-associated inflammation in colorectal carcinogenesis.

ABSTRACT: The role of inflammation in colorectal carcinogenesis may differ according to individuals' genetic variations. Therefore, we investigated whether genetic susceptibility alters the association between inflammatory potential of diet and the risk of colorectal cancer within the Korean population. We genotyped four polymorphisms in four genes (IL1B, TNF, PPARG, and PPARGC1A) and calculated the dietary inflammatory index (DII) in a case-control study with 701 colorectal cancer patients and 1,402 controls. Among the investigated polymorphisms, heterozygous carriers of rs3774921 in PPARGC1A showed a higher risk of colorectal cancer (OR [95% CI] = 1.26 [1.02-1.55] for TC vs. TT). When the data were stratified by rs3774921 genetic variant, the association of a pro-inflammatory diet with colorectal cancer risk was more prominent among homozygous variant allele carriers (OR [95% CI] = 5.15 [2.35-11.29] for high vs. low DII) (P for interaction = 0.009). When stratified by anatomic site, this association was much stronger for rectal cancer patients (OR [95% CI] = 8.06 [2.67-24.16] for high vs. low DII) (P for interaction = 0.006). Additionally, this interaction was stronger among those older than 50 years and not exercising regularly. Conversely, no association or interaction was found for the other investigated polymorphisms. In conclusion, the results of this study suggest that a pro-inflammatory diet may have a differential effect on colorectal cancer risk based on PPARGC1A genetic variation. This interaction may differ by anatomic location and other risk factors.

SUBMITTER: Cho YA

PROVIDER: S-EPMC5352421 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Genetic variation in PPARGC1A may affect the role of diet-associated inflammation in colorectal carcinogenesis.

Cho Young Ae YA Lee Jeonghee J Oh Jae Hwan JH Chang Hee Jin HJ Sohn Dae Kyung DK Shin Aesun A Kim Jeongseon J

Oncotarget 20170101 5

The role of inflammation in colorectal carcinogenesis may differ according to individuals' genetic variations. Therefore, we investigated whether genetic susceptibility alters the association between inflammatory potential of diet and the risk of colorectal cancer within the Korean population. We genotyped four polymorphisms in four genes (IL1B, TNF, PPARG, and PPARGC1A) and calculated the dietary inflammatory index (DII) in a case-control study with 701 colorectal cancer patients and 1,402 cont ...[more]

PMID: 28051997

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Project description:Hypercholesterolemia resulting in atherosclerosis is associated with an increased risk of ischemic heart disease and colorectal cancer (CRC). However, the roles of apoliprotein (Apo) E (Apoe) and low-density lipoprotein (Ldl) receptor (Ldlr) in colorectal carcinogenesis have not yet been investigated. In this study, we examined the susceptibility of Apoe-deficient and Ldlr-deficient mice, which are genetic animal models of atherosclerosis to azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colorectal carcinogenesis. In Experiment 1, male Apoe-deficient (n = 20) and wild type (WT) mice (C57BL/6J, n = 21) were treated with a single intraperitoneal (i.p.) injection of AOM (10 mg/kg body weight) and then given 1.5% DSS in drinking water for seven days. They were maintained up to week 20 and sacrificed for the histopathological examination of colorectal tumors. The mRNA expression of cyclooxygenase (Cox)-2, inducible nitric oxide synthase (Nos2), tumor necrosis factor (Tnf)-? interleukin (Il)-1?, and Il-6 was assayed in the colorectal mucosa. In Experiment 2, male Ldlr-deficient (n = 14) and WT mice (C57BL/6J, n = 10) were given a single i.p. injection of AOM (10 mg/kg body weight) and then given 2% DSS in drinking water for seven days. They were sacrificed at week 20 to evaluate their colorectum histopathologically. In Experiment 1, the multiplicity of CRCs was significantly higher in the Apoe-deficient mice (2.75 ± 1.48) than in the WT mice (0.62 ± 0.67). The serum lipoprotein levels in the Apoe-deficient mice were also significantly higher than in the WT mice. In Experiment 2, the incidence (29%) and multiplicity (0.50 ± 0.94) of CRCs in the Ldlr mice were significantly lower than in the WT mice (80% incidence and 3.10 ± 2.38 multiplicity). The mRNA expression of two inducible enzymes and certain pro-inflammatory cytokines in the colorectum of each genotype was greater than in the respective WT mice. The values in the Apoe-deficient mice were much greater than in the Ldlr mice. These findings suggest that Apoe-deficient mice showed increased susceptibility to inflammation-associated colorectal carcinogenesis due to their high reactivity to inflammatory stimuli.

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Genetic variation in PPARGC1A may affect the role of diet-associated inflammation in colorectal carcinogenesis.

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Genetic variation in PPARGC1A may affect the role of diet-associated inflammation in colorectal carcinogenesis.

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