Protective role of +294 T/C (rs2016520) polymorphism of PPARD in Mexican patients with colorectal cancer

Abstract

ABSTRACT. PPARD encodes for peroxisome proliferator-activated receptor delta, which plays a significant role in controlling lipid metabolism, atherosclerosis, inflammation, cancer growth, progression, and apoptosis. Accumulated evidence suggests that the polymorphism rs2016520 in PPARD is associated with lipid metabolism, obesity, metabolic syndrome, and type 2 diabetes mellitus. The aim of this study was to determine whether the single nucleotide polymorphism +294T/C (rs2016520) in PPARD is associated with colorectal cancer (CRC) in the Mexican population. Genomic DNA from 178 CRC patients and 97 healthy blood donors was analyzed. The polymorphism was identified by the polymerase chain reaction-restriction fragment length polymorphism method. Results demonstrated that patients with the T/C genotype for the +294T/C (rs2016520) polymorphism present a protective role against CRC [odds ratio (OR) = 0.39; 95% confidence interval (CI) = 0.22-0.69; P = 0.0008]. This association was also evident for the T/C genotype in the stratified analysis by tumor-nodemetastasis stages I+II (OR = 0.26, P = 0.0332) and III+IV (OR = 0.44, P = 0.0067). However, in the stratified analysis by tumor location, we observed an increased risk of rectal cancer (OR = 7.57, P = 0.0403) vs colon cancer (OR = 4.87, P = 0.234) in patients carrying the C/C genotype and under the dominant and recessive models of inheritance.In conclusion, for the first time, the association between the +294T/C (rs2016520) polymorphism and colorectal cancer has been studied in Mexican patients. Our results reveal that variations in PPARD may play a significant role in genetic susceptibility to colorectal cancer.

The Impact of PPARD and PPARG Polymorphisms on Glioma Risk and Prognosis

“…In our study, we firstly observed that PPARD polymorphisms (rs2016520, rs67056409 and rs1053049) were significantly associated with glioma risk. Similar association has been reported in colorectal cancer 39 . It suggests that PPARD polymorphisms could be involved in the susceptibility of glioma development.…”

“…In mice, expression of PPARδ is related to prognosis and metastatic ability of breast cancer cells 38 . Polymorphisms of PPARD and PPARG are associated with risk and prognosis of many diseases, including cardiovascular disease, diabetes, brain diseases, medulloblastoma and other cancers [39][40][41] . In our study, we firstly observed that PPARD polymorphisms (rs2016520, rs67056409 and rs1053049) were significantly associated with glioma risk.…”

Pro12Ala PPAR-γ2 and +294T/C PPAR-δ Polymorphisms and Association with Metabolic Traits in Teenagers from Northern Mexico

“…There is also an association between the C allele and BMI, glucose levels, height, and coronary heart disease (CHD) [ 24 , 26 , 27 , 29 , 30 , 31 , 32 , 33 , 34 ]. The prevalence of the C allele varies among different populations: 22.5% to 31.04% in Chinese people, 19.2% in Germans, 20.1% in French Canadians and 26% in Mexicans [ 22 , 25 , 28 , 35 , 36 ].…”

PPARδ Mediates the Effect of Dietary Fat in Promoting Colorectal Cancer Metastasis

“…However, the biological function of PPARd in tumorigenesis remains unclear and somewhat controversial. PPARd polymorphisms have been shown to be associated with colorectal cancer (22,23). Although investigation of PPARd expression in human colorectal cancer specimens generated disparate results (24,25), one report showed that the PPARd protein accumulated only in human colorectal cancer cells with a highly malignant morphology (25).…”