Genetic Variants of Peroxisome Proliferator-Activated Receptor δ Are Associated with Gastric Cancer
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Peroxisome proliferator-activated receptors (PPAR) are implicated in pathogenesis of insulin resistance and cancers of the digestive system.
We investigated the associations of single nucleotide polymorphisms (SNPs) of PPAR δ and γ with gastric cancer and explored interactions with risk factors of gastric cancer.
We conducted our analysis in a case–control study of 196 gastric cancer patients and 397 controls residing in the Taixing region of Jiangsu, China. Six SNPs in the PPARδ (rs2076167, rs3734254) and PPARγ genes (rs10865710, rs1801282, rs3856806, rs13306747) were genotyped. We employed logistic regression to evaluate the association between each genotype and gastric cancer and tested for gene–environment interaction with Helicobacter pylori (H. pylori) infection, smoking status, and meat and salt intake.
We found that the G/G variant rs2076167, in tight linkage disequilibrium with rs3734254 (R 2 = 0.97), was associated with increased risk of gastric cancer in a recessive model (OR 2.20, 95 % CI 1.12, 4.32). The association between G/G variant of rs2016167 and gastric cancer was particularly strong among those with higher salt intake (OR 5.11, 95 % CI 1.11, 23.5), but did not vary by H. pylori infection or smoking status.
We found that genetic variants of PPARδ were associated with gastric cancer. If the association is confirmed in larger studies, it may implicate a role for PPARδ activators, such as insulin-sensitizing agents, in prevention of gastric cancer.
KeywordsPeroxisome proliferator-activated receptors Gastric cancer Gene–environment interaction Salt
This project is supported by the Grant CA09412 from the National Cancer Institute, and ES 011667 from the National Institute of Environmental Health Sciences, the International Union Against Cancer (UICC) Technology Transfer fellowship (ICRETT) awarded to Dr. Li-Na Mu, as well as a NIH/NCI postdoctoral fellowship (R25 CA 87949) awarded to Dr. Christie Jeon. The study was also partially supported by the Alper Program of Environmental Genomics of UCLA’s Jonsson Comprehensive Cancer Center.
Conflict of interest
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