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Genetic Variants of Peroxisome Proliferator-Activated Receptor δ Are Associated with Gastric Cancer

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Abstract

Background

Peroxisome proliferator-activated receptors (PPAR) are implicated in pathogenesis of insulin resistance and cancers of the digestive system.

Aim

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.

Methods

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.

Results

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.

Conclusion

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.

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Acknowledgments

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

None.

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Authors and Affiliations

  1. Department of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Blvd., SCCT 1S33, Los Angeles, CA, 90048, USA

    Christie Jeon

  2. Center for Cancer Prevention and Control Research, Fielding School of Public Health, University of California Los Angeles, 650 Charles E Young Drive South, A2-125 CHS, Los Angeles, CA, 90095, USA

    Christie Jeon, Jian-Yu Rao & Zuo-Feng Zhang

  3. Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles, 650 Charles E Young Drive South, 73-271 CHS, Los Angeles, CA, 90095, USA

    Shen-Chih Chang & Zuo-Feng Zhang

  4. Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, SUNY, 273A Farber Hall, Buffalo, NY, 14214, USA

    Lina Mu

  5. Department of Non-communicable Chronic Disease Control, Jiangsu Provincial Center for Disease Control and Prevention, Jiangsu Rd., Nanjing, 210009, Jiangsu, People’s Republic of China

    Jinkou Zhao

  6. Departments of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Ave., 13-188 CHS, Los Angeles, CA, 90095, USA

    Jian-Yu Rao

  7. Center for Human Nutrition, David Geffen School of Medicine, University of California Los Angeles, 900 Veteran Ave. 14-165, Los Angeles, CA, 90095, USA

    Qing-Yi Lu

  8. Department of Epidemiology, UCLA School of Public Health, 71-225 CHS, 650 Charles E Young Drive, South, Box 951772, Los Angeles, CA, 90095-1772, USA

    Zuo-Feng Zhang

Authors
  1. Christie Jeon
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  2. Shen-Chih Chang
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  3. Lina Mu
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  4. Jinkou Zhao
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  5. Jian-Yu Rao
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  6. Qing-Yi Lu
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  7. Zuo-Feng Zhang
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Corresponding author

Correspondence to Zuo-Feng Zhang.

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Jeon, C., Chang, SC., Mu, L. et al. Genetic Variants of Peroxisome Proliferator-Activated Receptor δ Are Associated with Gastric Cancer. Dig Dis Sci 58, 2881–2886 (2013). https://doi.org/10.1007/s10620-013-2770-2

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  • DOI: https://doi.org/10.1007/s10620-013-2770-2

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