title: 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.
authors.affiliation: Molecular Epidemiology Branch, National Cancer Center, Goyang, South Korea.
authors.forename: Young Ae
authors.initials: YA
authors.lastname: Cho
authors.affiliation: Molecular Epidemiology Branch, National Cancer Center, Goyang, South Korea.
authors.forename: Jeonghee
authors.initials: J
authors.lastname: Lee
authors.affiliation: Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Goyang, South Korea.
authors.forename: Jae Hwan
authors.initials: JH
authors.lastname: Oh
authors.affiliation: Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Goyang, South Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Chang
authors.affiliation: Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Goyang, South Korea.
authors.forename: Dae Kyung
authors.initials: DK
authors.lastname: Sohn
authors.affiliation: Molecular Epidemiology Branch, National Cancer Center, Goyang, South Korea.|Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Aesun
authors.initials: A
authors.lastname: Shin
authors.affiliation: Molecular Epidemiology Branch, National Cancer Center, Goyang, South Korea.
authors.forename: Jeongseon
authors.initials: J
authors.lastname: Kim
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D004032:Diet / Q000009:adverse effects* / Q000208:ethnology; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
keywords: PPARGC1A; diet; inflammation; interaction; polymorphism