Association between PPARγ, PPARGC1A, and PPARGC1B genetic variants and susceptibility of gastric cancer in an Eastern Chinese population

Purpose: Previous studies showed that peroxisome proliferator-activated receptor gamma (PPAR gamma) and PPAR gamma coactivator1 family (PPARGC1A and PPARGC1B) gene single nucleotide variants (SNVs)were strongly associated with cancer susceptibility. The purpose of this study was to investigate the association of PPAR gamma, PPARGC1A, and PPARGC1B variants with the risk of gastric cancer (GC). Patients and methods: We performed a case-control study of 490 GC cases and 1,476 healthy controls from eastern China. PPAR gamma rs1801282 C > G, rs3856806 C > T, PPARGC1A rs2970847 C > T, rs8192678 C > T and PPARGC1B rs7732671 G > C, rs17572019 G > A SNVs were selected to investigate the association between these SNVs and GC susceptibility. Genotypes of the SNVs were assessed by multiplex fluorescent PCR using a custom-by-design 48-Plex SNPscan (TM) Kit. Results: The PPAR gamma rs1801282 SNV was associated with a decreased risk for GC (GC vs. CC: odds ratio (OR) = 0.62, 95% confidence interval (95%CI) = 0.42-0.93, adjusted P = 0.019; GC + GG vs. GG: OR = 0.63 95%CI = 0.42-0.93, adjusted P = 0.019; respectively). In addition, stratified analysis revealed that the PPAR gamma rs1801282 SNV was correlated with the risk of GC in subgroups of age >= 61, no smoking, and no alcohol consuming. We also confirmed that the PPAR gamma rs3856806 C > T SNV promoted the risk of GC in women. The PPARGC1A rs8192678 TT genotype decreased the susceptibility of GC in men. The PPARGC1A rs2970847 C > T SNV decreased the susceptibility of GC in the subgroup of BMI >= 24 kg/m(2). The PPARGC1B rs7732671 G > C and rs17572019 G > A SNVs promoted the risk of GC in the subgroup of BMI >= 24 kg/m(2). Conclusion: This study indicates that the PPAR gamma, PPARGC1A, and PPARGC1B SNVs may be associated with the susceptibility of GC in eastern Chinese population. Future studies with larger populations, detailed H. pylori infection status for subgroup analysis, and functional study are needed to further clarify the relationship between these SNVs and GC risk.