Abstract
Recent studies showed that peroxisome proliferator-activated receptors (PPARs) had effects on the progression of multiple tumors, but the role of PPARD and PPARG in glioma remains poorly understand. We conducted a case-control study to investigate the association of polymorphisms in PPARD and PPARG with glioma risk and prognosis in the Chinese Han population. Seven polymorphisms (PPARD: rs2016520, rs67056409, rs1053049 and rs2206030; PPARG: rs2920503, rs4073770 and rs1151988) were genotyped using the Agena MassARRAY system in 568 glioma patients and 509 healthy controls. The odd ratios (OR) and 95% confidence interval (CI) were calculated to assess the association of PPARD and PPARG polymorphisms with glioma risk. The Multifactor dimensionality reduction (MDR) method was used to analysis interactions of genetic polymorphisms on glioma risk. Then, we conducted log-rank test, Kaplan-Meier analysis and Cox regression model to evaluate the relationship of PPARD and PPARG polymorphisms with glioma prognosis. We found PPARD polymorphisms (rs2016520, rs67056409, rs1053049) were significantly associated with glioma risk in multiple models (P < 0.05). Stratified analysis showed rs2016520, rs67056409, rs1053049 of PPARD significantly decreased risk of glioma in the subgroup of age > 40 and astrocytoma (P < 0.05). For male, PPARD rs1053049 had a strong relationship with glioma risk in allele (P = 0.041), dominant (P = 0.040) and additive (P = 0.040) models. The effect of PPARG rs2920503 on glioma risk was related to glioma grade (P < 0.05). MDR showed that a seven-locus model was the best polymorphisms interaction pattern. Moreover, surgery and chemotherapy had strongly impact on overall survival and progression free survival of glioma patients. Our findings suggested that PPARD and PPARG polymorphisms were associated with glioma risk and prognosis in the Chinese Han population, and further studies are need to confirm our results.
Highlights
Glioma is the most common type of malignant brain tumors in the central nervous system (CNS), accounting for approximately 80% of primary brain tumors[1]
The results showed PPARG rs2920503 was strongly related to higher risk of high-grade glioma (III + IV) in co-dominant (OR = 2.04, 95%confidence interval (CI) = 1.13–3.68, P = 0.018) and recessive (OR = 2.03, 95%CI = 1.15–3.57, P = 0.014) models
We did not observe significantly association of PPARD and PPARG polymorphisms with overall survival (OS) and progression free survival (PFS) of glioma patients (P > 0.05, Supplemental Table 3). In this case-control study, we examined the association of PPARD and PPARG polymorphisms with glioma risk and prognosis in the Chinese Han population
Summary
Glioma is the most common type of malignant brain tumors in the central nervous system (CNS), accounting for approximately 80% of primary brain tumors[1]. Increasing studies are focused on the role of Peroxisome proliferator-activated receptors (PPARs) polymorphisms on cancer. PPARD encodes PPARδ, a nuclear hormone receptor that implicated in varieties of biological processes, including epidermal cell proliferation, migration, lipid and glucose metabolism[6,7,8]. Previous studies revealed that PPARD polymorphisms were associated with lipid levels, metabolic traits, obesity and risk of coronary heart diseases (CHD) and cancers[16,17,18,19]. PPARG is located in human chromosome 3p25 and encodes a nuclear receptor (PPARγ) activated by fatty acid metabolites or synthetic medicines[24,25,26]. We conducted a case-control study to investigate the association of PPARD and PPARG polymorphisms (rs2016520, rs67056409, rs1053049, rs2206030, rs2920503, rs4073770 and rs1151988) with glioma risk and prognosis in the Chinese Han population
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