DOI QR코드

DOI QR Code

Peroxisome Proliferator-Activated Receptor-Gamma Pro12Ala Polymorphism Could be a Risk Factor for Gastric Cancer

  • Zhao, Jing ;
  • Zhi, Zheng ;
  • Song, Guangyao ;
  • Wang, Juan ;
  • Wang, Chao ;
  • Ma, Huijuan ;
  • Yu, Xian ;
  • Sui, Aixia ;
  • Zhang, Hongtao
  • Published : 2015.04.03

Abstract

Background: Due to the strong inhibitory effects of $PPAR{\gamma}$ gene on the growth of cancer cells, the role of Pro12Ala polymorphism in $PPAR{\gamma}$ gene has been extensively investigated in cancer recently. However, the results were inconsistent according to cancer type. The aim of this study was to comprehensively evaluate the $PPAR{\gamma}$ Pro12Ala polymorphism and gastric cancer susceptibility. Materials and Methods: Search strategies were conducted in Pubmed, Medline (Ovid), Chinese biomedical database (CBM), China national knowledge infrastructure (CNKI), VIP, and Wanfang database, covering all publications, with the last search up to November 01, 2014. The strength of association between $PPAR{\gamma}$ Pro12Ala polymorphism and gastric cancer risk was assessed by OR with 95%CI. Results: A total of 546 cases and 827 controls in 5 case-control studies were included in this meta-analysis. The results indicated that the variant G allele carriers (CG+GG) had a 2.31 times higher risk for gastric cancer when compared with the homozygote CC (odds ratio (OR)=2.31, 95% confidence interval (CI)=1.67-3.21 for CG+GG vs. CC). In the subgroup analysis by ethnicity, significantly elevated risks were both found in Asians (OR=2.56, 95% CI=1.42-4.64) and Caucasians (OR=2.20, 95% CI=1.48-3.25). Similarly, in the subgroup analysis by H. pylori status, a significantly increased risk was identified in H. pylori (+) populations (OR=3.68, 95%CI=2.07-6.52), but not in H. pylori(-) populations (OR=1.17, 95%CI=0.58-2.39). Conclusions: This pooled analysis suggested that the $PPAR{\gamma}$ Pro12Ala polymorphism could be an independent predictive risk factor for gastric cancer especially in H. pylori infected populations in Asians and Caucasians. Nevertheless, prospectively designed cohort studies are needed to further investigate gene-gene and gene-environment interactions to confirm the combined effects of $PPAR{\gamma}$ Pro12Ala polymorphisms and H. pylori infection on gastric cancer risk.

Keywords

Peroxisome proliferator-activated receptor ${\gamma}(PPAR{\gamma})$;polymorphism;gastric cancer

References

  1. Ajani JA, Bentrem DJ, Besh S, et al (2013). Gastric cancer, version 2.2013: featured updates to the NCCN guidelines. J Natl Compr Canc Netw, 11, 531-46.
  2. Auwerx J (2002). Nuclear receptors. I. PPAR gamma in the gastrointestinal tract: gain or pain? Am J Physiol Gastrointest Liver Physiol, 282, 581-5. https://doi.org/10.1152/ajpgi.00508.2001
  3. Bazargani A, Khoramrooz SS, Kamali-Sarvestani E, et al (2010). Association between peroxisome proliferator-activated receptor-gamma gene polymorphism (Pro12Ala) and Helicobacter pylori infection in gastric carcinogenesis. Scand J Gastroenterol, 45, 1162-7. https://doi.org/10.3109/00365521.2010.499959
  4. Begg CB, Mazumdar M (1994). Operating characteristics of a rank correlation test for publication bias. Biometrics, 50, 1088-101. https://doi.org/10.2307/2533446
  5. Bringeland EA, Wasmuth HH, Fougner R, et al (2014). Impact of perioperative chemotherapy on oncological outcomes after gastric cancer surgery. Br J Surg, 101, 1712-20. https://doi.org/10.1002/bjs.9650
  6. Campa D, Zienolddiny S, Maggini V, et al (2004). Association of a common polymorphism in the cyclooxygenase 2 gene with risk of non-small cell lung cancer. Carcinogenesis, 25, 229-35.
  7. Canbay E, Kurnaz O, Canbay B, et al (2012). PPAR-gamma Pro12Ala polymorphism and gastric cancer risk in a Turkish population. Asian Pac J Cancer Prev, 13, 5875-8. https://doi.org/10.7314/APJCP.2012.13.11.5875
  8. Chen G, Shen ZL, Wang L, et al (2013).Hsa-miR-181a-5p expression and effects on cell proliferation in gastric cancer. Asian Pac J Cancer Prev, 14, 3871-5. https://doi.org/10.7314/APJCP.2013.14.6.3871
  9. Cheon CW, Kim DH, Kim DH (2009). Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol, 15, 310-20. https://doi.org/10.3748/wjg.15.310
  10. Chinetti G, Fruchart JC, Staels B (2000). Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation. Inflamm Res, 49, 497-505. https://doi.org/10.1007/s000110050622
  11. Deeb SS, Fajas L, Nemoto M, et al (1998). A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet, 20, 284-7. https://doi.org/10.1038/3099
  12. Elbrecht A, Chen Y, Cullinan CA, et al (1996). Molecular cloning, expression and characterization of human peroxisome proliferator activated receptors gamma 1 and gamma 2. Biochem Biophys Res Commun, 224, 431-7. https://doi.org/10.1006/bbrc.1996.1044
  13. Gouda HN, Sagoo GS, Harding AH, et al (2010). The association between the peroxisome proliferator-activated receptor-gamma2 (PPARG2) Pro12Ala gene variant and type 2 diabetes mellitus: a HuGE review and meta-analysis. Am J Epidemiol, 171, 645-55. https://doi.org/10.1093/aje/kwp450
  14. Greene ME, Blumberg B, McBride OW, et al (1995). Isolation of the human peroxisome proliferator activated receptor gamma cDNA: expression in hematopoietic cells and chromosomal mapping. Gene Expr, 4, 281-99.
  15. Grommes C, Landreth GE, Heneka MT (2004). Antineoplastic effects of peroxisome proliferator-activated receptor gamma agonists. Lancet Oncol, 5, 419-29. https://doi.org/10.1016/S1470-2045(04)01509-8
  16. Guggenheim DE, Shah MA (2013). Gastric cancer epidemiology and risk factors. J Surg Oncol, 107, 230-6. https://doi.org/10.1002/jso.23262
  17. Gupta RA, Polk DB, Krishna U, et al (2001). Activation of peroxisome proliferator-activated receptor $\gamma$ suppresses nuclear factor ${\kappa}B$-mediated apoptosis induced by Helicobacter pylori in gastric epithelial cells. J Biological Chemistry, 276, 31059-66. https://doi.org/10.1074/jbc.M104141200
  18. Huguenin GV, Rosa G (2010). The Ala allele in the PPAR-gamma2 gene is associated with reduced risk of type 2 diabetes mellitus in caucasians and improved insulin sensitivity in overweight subjects. Br J Nutr, 104, 488-97. https://doi.org/10.1017/S0007114510000851
  19. Ji AJ, Liu SL, Ju WZ, et al (2014). Anti-proliferation effects and molecular mechanisms of action of tetramethypyrazine on human SGC-7901 gastric carcinoma cells. Asian Pac J Cancer Prev, 15, 3581-6. https://doi.org/10.7314/APJCP.2014.15.8.3581
  20. Karimi P, Islami F, Anandasabapathy S (2014). Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev, 23, 700-13. https://doi.org/10.1158/1055-9965.EPI-13-1057
  21. Konturek PC, Kania J, Konturek JW, et al (2003). H. pylori infection, atrophic gastritis, cytokines, gastrin, COX-2, PPAR gamma and impaired apoptosis in gastric carcinogenesis. Med Sci Monit, 9, 53-66.
  22. Lee JM, Kim SS, Cho YS (2012). The role of PPARgamma in helicobacter pylori infection and gastric carcinogenesis. PPAR Res, 2012, 687570.
  23. Leung WK, Bai AH, Chan VY, et al (2004). Effect of peroxisome proliferator activated receptor gamma ligands on growth and gene expression profiles of gastric cancer cells. Gut, 53, 331-8. https://doi.org/10.1136/gut.2003.021105
  24. Liao SY, Zeng ZR, Leung WK, et al (2006). Peroxisome proliferator-activated receptor-gamma Pro12Ala polymorphism, Helicobacter pylori infection and non-cardia gastric carcinoma in Chinese. Aliment Pharmacol Ther, 23, 289-94. https://doi.org/10.1111/j.1365-2036.2006.02739.x
  25. Liao SY ZZ, Zhou SZ, Chen B, et al (2007). Association of Pro12Ala polymorphism in the Peroxisome proliferator activated receptor gamma2 with gastric cancers in China. Chinese J Pathophys, 23, 757-60.
  26. Liu J, Huang XE, Tian GY, et al (2013). Phase II study on safety and efficacy of yadanzi (javanica oil emulsion injection) combined with chemotherapy for patients with gastric cancer. Asian Pac J Cancer Prev, 14, 2009-12. https://doi.org/10.7314/APJCP.2013.14.3.2009
  27. Liu J, Huang XE, Feng JF (2014). Further study on pemetrexed based chemotherapy in treating patients with advanced gastric cancer (AGC). Asian Pac J Cancer Prev, 15, 6587-90. https://doi.org/10.7314/APJCP.2014.15.16.6587
  28. Lu J, Imamura K, Nomura S, et al (2005). Chemopreventive effect of peroxisome proliferator-activated receptor gamma on gastric carcinogenesis in mice. Cancer Res, 65, 4769-74. https://doi.org/10.1158/0008-5472.CAN-04-2293
  29. Lu YL, Li GL, Huang HL, et al (2010). Peroxisome proliferator-activated receptor-gamma 34C>G polymorphism and colorectal cancer risk: a meta-analysis. World J Gastroenterol, 16, 2170-5. https://doi.org/10.3748/wjg.v16.i17.2170
  30. Mao Q, Guo H, Gao L, et al (2013). Peroxisome proliferator-activated receptor gamma2 Pro12Ala (rs1801282) polymorphism and breast cancer susceptibility: a meta-analysis. Mol Med Rep, 8, 1773-8.
  31. Michalik L, Desvergne B, Wahli W (2004). Peroxisome-proliferator-activated receptors and cancers: complex stories. Nat Rev Cancer, 4, 61-70. https://doi.org/10.1038/nrc1254
  32. Milne AN, Carneiro F, O'Morain C, et al (2009). Nature meets nurture: molecular genetics of gastric cancer. Hum Genet, 126, 615-28. https://doi.org/10.1007/s00439-009-0722-x
  33. Nagao M, Sato Y, Yamauchi A (2014). A meta-analysis of the association of PPARgamma rs1801282 polymorphism and NSAID usage with the risk of developing cancer. Biol Pharm Bull, 37, 1062-7. https://doi.org/10.1248/bpb.b14-00160
  34. Nakajima A, Wada K, Miki H, et al (2001). Endogenous PPAR gamma mediates anti-inflammatory activity in murine ischemia-reperfusion injury. Gastroenterol, 120, 460-9. https://doi.org/10.1053/gast.2001.21191
  35. Nolte RT, Wisely GB, Westin S, et al (1998). Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma. Nature, 395, 137-43. https://doi.org/10.1038/25931
  36. Paltoo D, Woodson K, Taylor P, et al (2003). Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) gene and risk of prostate cancer among men in a large cancer prevention study. Cancer Lett, 191, 67-74. https://doi.org/10.1016/S0304-3835(02)00617-1
  37. Paynter RA, Hankinson SE, Colditz GA, et al (2004). No evidence of a role for PPARgamma Pro12Ala polymorphism in endometrial cancer susceptibility. Pharmacogenetics, 14, 851-6. https://doi.org/10.1097/00008571-200412000-00008
  38. Pereira AC, Oliveira R, Castro AC, et al (2013). Does pro (12)ala polymorphism enhance the physiological role of PPARgamma2? PPAR Res, 2013, 401274.
  39. Pinheiro SP, Gates MA, De Vivo I, et al (2010). Interaction between use of non-steroidal anti-inflammatory drugs and selected genetic polymorphisms in ovarian cancer risk. Int J Mol Epidemiol Genet, 1, 320-31.
  40. Polk DB, Peek RM, Jr (2010). Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer, 10, 403-14. https://doi.org/10.1038/nrc2857
  41. Prasad KN, Saxena A, Ghoshal UC, et al (2008). Analysis of Pro12Ala PPAR gamma polymorphism and Helicobacter pylori infection in gastric adenocarcinoma and peptic ulcer disease. Ann Oncol, 19, 1299-303. https://doi.org/10.1093/annonc/mdn055
  42. Saeki N, Ono H, Sakamoto H, et al (2013). Genetic factors related to gastric cancer susceptibility identified using a genome-wide association study. Cancer Sci, 104, 1-8. https://doi.org/10.1111/cas.12042
  43. Sato H, Ishihara S, Kawashima K, et al (2000). Expression of peroxisome proliferator-activated receptor (PPAR) $\gamma$ in gastric cancer and inhibitory effects of PPAR$\gamma$ agonists. British J Cancer, 83, 1394. https://doi.org/10.1054/bjoc.2000.1457
  44. (1994). Schistosomes, liver flukes and helicobacter pylori. iarc working group on the evaluation of carcinogenic risks to humans. lyon, 7-14 June 1994. IARC Monogr Eval Carcinog Risks Hum, 61, 1-241.
  45. Shen XB, Wang J, Li PF, et al (2014). Screening of susceptibility genes and multi-gene risk analysis in gastric cancer. Med Oncol, 31, 196. https://doi.org/10.1007/s12032-014-0196-0
  46. Shi J, Qu YP, Hou P (2014). Pathogenetic mechanisms in gastric cancer. World J Gastroenterol, 20, 13804-19. https://doi.org/10.3748/wjg.v20.i38.13804
  47. Siegel R, Ma J, Zou Z, et al (2014). Cancer statistics 2014. CA Cancer J Clin, 64, 9-29. https://doi.org/10.3322/caac.21208
  48. Tahara T, Arisawa T, Shibata T, et al (2008). Influence of peroxisome proliferator-activated receptor (PPAR)gamma Plo12Ala polymorphism as a shared risk marker for both gastric cancer and impaired fasting glucose (IFG) in Japanese. Dig Dis Sci, 53, 614-21. https://doi.org/10.1007/s10620-007-9944-8
  49. Theocharis S, Margeli A, Vielh P, et al (2004). Peroxisome proliferator-activated receptor-gamma ligands as cell-cycle modulators. Cancer Treat Rev, 30, 545-54. https://doi.org/10.1016/j.ctrv.2004.04.004
  50. Wei GL, Huang XE, Huo JG, et al (2013).Phase II study on pemetrexed-based chemotherapy in treating patients with metastatic gastric cancer not responding to prior palliative chemotherapy. Asian Pac J Cancer Prev, 14, 2703-6. https://doi.org/10.7314/APJCP.2013.14.5.2703
  51. Xu X, Wang L, Xu HQ, et al (2013). Clinical comparison between paclitaxel liposome (Lipusu) and paclitaxel for treatment of patients with metastatic gastric cancer. Asian Pac J Cancer Prev, 14, 2591-4. https://doi.org/10.7314/APJCP.2013.14.4.2591
  52. Xu W, Li Y, Wang X, et al (2010). PPARgamma polymorphisms and cancer risk: a meta-analysis involving 32,138 subjects. Oncol Rep, 24, 579-85.
  53. Yen CJ, Beamer BA, Negri C, et al (1997). Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR gamma) gene in diabetic caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation. Biochem Biophys Res Commun, 241, 270-4. https://doi.org/10.1006/bbrc.1997.7798
  54. Yin M, Hu Z, Tan D, et al (2009). Molecular epidemiology of genetic susceptibility to gastric cancer: focus on single nucleotide polymorphisms in gastric carcinogenesis. Am J Transl Res, 1, 44-54.
  55. Zhang H, Bi Y, Hu C, et al (2012). Association between the Pro12Ala polymorphism of PPAR-$\gamma$ gene and the polycystic ovary syndrome: A meta-analysis of case-control studies. Gene, 503, 12-17. https://doi.org/10.1016/j.gene.2012.04.083
  56. Zhao F, Zhu H, Huang M, et al (2014). The 765G>C polymorphism in the cyclooxygenase-2 gene and gastric cancer risk: an update by meta-analysis. Asian Pac J Cancer Prev, 15, 2863-8. https://doi.org/10.7314/APJCP.2014.15.6.2863
  57. Zmuda JM, Modugno F, Weissfeld JL, et al (2006). Peroxisome proliferator-activated receptor-gamma polymorphism, body mass and prostate cancer risk: evidence for gene-environment interaction. Oncol, 70, 185-9. https://doi.org/10.1159/000093805