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Published in: Digestive Diseases and Sciences 10/2013

01-10-2013 | Original Article

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

Authors: Christie Jeon, Shen-Chih Chang, Lina Mu, Jinkou Zhao, Jian-Yu Rao, Qing-Yi Lu, Zuo-Feng Zhang

Published in: Digestive Diseases and Sciences | Issue 10/2013

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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.
Literature
1.
go back to reference GLOBOCAN 2008 v2.0. Cancer incidence and mortality worldwide [database on the Internet]. International Agency for Research on Cancer. 2010. Available from: http://globocan.iarc.fr. Accessed 10 May 2013. GLOBOCAN 2008 v2.0. Cancer incidence and mortality worldwide [database on the Internet]. International Agency for Research on Cancer. 2010. Available from: http://​globocan.​iarc.​fr. Accessed 10 May 2013.
2.
go back to reference Bray F, Ren JS, Masuyer E, Ferlay J. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer. 2013;132:1133–1145. Bray F, Ren JS, Masuyer E, Ferlay J. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer. 2013;132:1133–1145.
3.
go back to reference Terry MB, Gaudet MM, Gammon MD. The epidemiology of gastric cancer. Semin Radiat Oncol. 2002;12:111–127.PubMedCrossRef Terry MB, Gaudet MM, Gammon MD. The epidemiology of gastric cancer. Semin Radiat Oncol. 2002;12:111–127.PubMedCrossRef
4.
go back to reference Guilford P, Hopkins J, Harraway J, et al. E-cadherin germline mutations in familial gastric cancer. Nature. 1998;392:402–405.PubMedCrossRef Guilford P, Hopkins J, Harraway J, et al. E-cadherin germline mutations in familial gastric cancer. Nature. 1998;392:402–405.PubMedCrossRef
5.
go back to reference Youssef J, Badr M. Peroxisome proliferator-activated receptors and cancer: challenges and opportunities. Br J Pharmacol. 2011;164:68–82.PubMedCrossRef Youssef J, Badr M. Peroxisome proliferator-activated receptors and cancer: challenges and opportunities. Br J Pharmacol. 2011;164:68–82.PubMedCrossRef
6.
go back to reference Peters JM, Gonzalez FJ. Sorting out the functional role(s) of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) in cell proliferation and cancer. Biochim Biophys Acta. 2009;1796:230–241.PubMed Peters JM, Gonzalez FJ. Sorting out the functional role(s) of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) in cell proliferation and cancer. Biochim Biophys Acta. 2009;1796:230–241.PubMed
7.
go back to reference Girroir EE, Hollingshead HE, He P, Zhu B, Perdew GH, Peters JM. Quantitative expression patterns of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) protein in mice. Biochem Biophys Res Commun. 2008;371:456–461.PubMedCrossRef Girroir EE, Hollingshead HE, He P, Zhu B, Perdew GH, Peters JM. Quantitative expression patterns of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) protein in mice. Biochem Biophys Res Commun. 2008;371:456–461.PubMedCrossRef
8.
go back to reference Prasad KN, Saxena A, Ghoshal UC, Bhagat MR, Krishnani N. Analysis of Pro12Ala PPAR gamma polymorphism and Helicobacter pylori infection in gastric adenocarcinoma and peptic ulcer disease. Ann Oncol. 2008;19:1299–1303.PubMedCrossRef Prasad KN, Saxena A, Ghoshal UC, Bhagat MR, Krishnani N. Analysis of Pro12Ala PPAR gamma polymorphism and Helicobacter pylori infection in gastric adenocarcinoma and peptic ulcer disease. Ann Oncol. 2008;19:1299–1303.PubMedCrossRef
9.
go back to reference Tahara T, Arisawa T, Shibata T, et al. 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. 2008;53:614–621.PubMedCrossRef Tahara T, Arisawa T, Shibata T, et al. 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. 2008;53:614–621.PubMedCrossRef
10.
go back to reference Larsson SC, Orsini N, Wolk A. Processed meat consumption and stomach cancer risk: a meta-analysis. J Natl Cancer Inst. 2006;98:1078–1087.PubMedCrossRef Larsson SC, Orsini N, Wolk A. Processed meat consumption and stomach cancer risk: a meta-analysis. J Natl Cancer Inst. 2006;98:1078–1087.PubMedCrossRef
11.
go back to reference Villegas R, Yang G, Liu D, et al. Validity and reproducibility of the food-frequency questionnaire used in the Shanghai men’s health study. Br J Nutr. 2007;97:993–1000.PubMedCrossRef Villegas R, Yang G, Liu D, et al. Validity and reproducibility of the food-frequency questionnaire used in the Shanghai men’s health study. Br J Nutr. 2007;97:993–1000.PubMedCrossRef
12.
go back to reference Shu XO, Yang G, Jin F, et al. Validity and reproducibility of the food frequency questionnaire used in the Shanghai Women’s Health Study. Eur J Clin Nutr. 2004;58:17–23.PubMedCrossRef Shu XO, Yang G, Jin F, et al. Validity and reproducibility of the food frequency questionnaire used in the Shanghai Women’s Health Study. Eur J Clin Nutr. 2004;58:17–23.PubMedCrossRef
13.
go back to reference Colmers IN, Bowker SL, Johnson JA. Thiazolidinedione use and cancer incidence in type 2 diabetes: a systematic review and meta-analysis. Diabetes Metab. 2012;38:475–484. Colmers IN, Bowker SL, Johnson JA. Thiazolidinedione use and cancer incidence in type 2 diabetes: a systematic review and meta-analysis. Diabetes Metab. 2012;38:475–484.
14.
go back to reference Wu CW, Yu J, Sung JJ. Peroxisome proliferator-activated receptor delta and gastric cancer (review). Oncol Rep. 2009;22:451–457.PubMed Wu CW, Yu J, Sung JJ. Peroxisome proliferator-activated receptor delta and gastric cancer (review). Oncol Rep. 2009;22:451–457.PubMed
15.
go back to reference Shan W, Nicol CJ, Ito S, et al. Peroxisome proliferator-activated receptor-beta/delta protects against chemically induced liver toxicity in mice. Hepatology. 2008;47:225–235.PubMedCrossRef Shan W, Nicol CJ, Ito S, et al. Peroxisome proliferator-activated receptor-beta/delta protects against chemically induced liver toxicity in mice. Hepatology. 2008;47:225–235.PubMedCrossRef
16.
go back to reference Harman FS, Nicol CJ, Marin HE, Ward JM, Gonzalez FJ, Peters JM. Peroxisome proliferator-activated receptor-delta attenuates colon carcinogenesis. Nat Med. 2004;10:481–483.PubMedCrossRef Harman FS, Nicol CJ, Marin HE, Ward JM, Gonzalez FJ, Peters JM. Peroxisome proliferator-activated receptor-delta attenuates colon carcinogenesis. Nat Med. 2004;10:481–483.PubMedCrossRef
17.
go back to reference Reed KR, Sansom OJ, Hayes AJ, et al. PPARdelta status and Apc-mediated tumourigenesis in the mouse intestine. Oncogene. 2004;23:8992–8996.PubMedCrossRef Reed KR, Sansom OJ, Hayes AJ, et al. PPARdelta status and Apc-mediated tumourigenesis in the mouse intestine. Oncogene. 2004;23:8992–8996.PubMedCrossRef
18.
go back to reference Barak Y, Liao D, He W, et al. Effects of peroxisome proliferator-activated receptor delta on placentation, adiposity, and colorectal cancer. Proc Natl Acad Sci USA. 2002;99:303–308.PubMedCrossRef Barak Y, Liao D, He W, et al. Effects of peroxisome proliferator-activated receptor delta on placentation, adiposity, and colorectal cancer. Proc Natl Acad Sci USA. 2002;99:303–308.PubMedCrossRef
19.
go back to reference Gupta RA, Wang D, Katkuri S, Wang H, Dey SK, DuBois RN. Activation of nuclear hormone receptor peroxisome proliferator-activated receptor-delta accelerates intestinal adenoma growth. Nat Med. 2004;10:245–247.PubMedCrossRef Gupta RA, Wang D, Katkuri S, Wang H, Dey SK, DuBois RN. Activation of nuclear hormone receptor peroxisome proliferator-activated receptor-delta accelerates intestinal adenoma growth. Nat Med. 2004;10:245–247.PubMedCrossRef
20.
go back to reference Wang XQ, Terry PD, Yan H. Review of salt consumption and stomach cancer risk: epidemiological and biological evidence. World J Gastroenterol. 2009;15:2204–2213.PubMedCrossRef Wang XQ, Terry PD, Yan H. Review of salt consumption and stomach cancer risk: epidemiological and biological evidence. World J Gastroenterol. 2009;15:2204–2213.PubMedCrossRef
21.
go back to reference Kumar AP, Quake AL, Chang MK, et al. Repression of NHE1 expression by PPAR gamma activation is a potential new approach for specific inhibition of the growth of tumor cells in vitro and in vivo. Cancer Res. 2009;69:8636–8644.PubMedCrossRef Kumar AP, Quake AL, Chang MK, et al. Repression of NHE1 expression by PPAR gamma activation is a potential new approach for specific inhibition of the growth of tumor cells in vitro and in vivo. Cancer Res. 2009;69:8636–8644.PubMedCrossRef
22.
go back to reference Fais S, De Milito A, You H, Qin W. Targeting vacuolar H+ ATPases as a new strategy against cancer. Cancer Res. 2007;67:10627–10630.PubMedCrossRef Fais S, De Milito A, You H, Qin W. Targeting vacuolar H+ ATPases as a new strategy against cancer. Cancer Res. 2007;67:10627–10630.PubMedCrossRef
23.
go back to reference Cavaleiro-Pinto M, Peleteiro B, Lunet N, Barros H. Helicobacter pylori infection and gastric cardia cancer: systematic review and meta-analysis. Cancer Causes Control. 2011;22:375–387.PubMedCrossRef Cavaleiro-Pinto M, Peleteiro B, Lunet N, Barros H. Helicobacter pylori infection and gastric cardia cancer: systematic review and meta-analysis. Cancer Causes Control. 2011;22:375–387.PubMedCrossRef
24.
go back to reference Camorlinga-Ponce M, Flores-Luna L, Lazcano-Ponce E, et al. Age and severity of mucosal lesions influence the performance of serologic markers in Helicobacter pylori-associated gastroduodenal pathologies. Cancer Epidemiol Biomarkers Prev. 2008;17:2498–2504.PubMedCrossRef Camorlinga-Ponce M, Flores-Luna L, Lazcano-Ponce E, et al. Age and severity of mucosal lesions influence the performance of serologic markers in Helicobacter pylori-associated gastroduodenal pathologies. Cancer Epidemiol Biomarkers Prev. 2008;17:2498–2504.PubMedCrossRef
Metadata
Title
Genetic Variants of Peroxisome Proliferator-Activated Receptor δ Are Associated with Gastric Cancer
Authors
Christie Jeon
Shen-Chih Chang
Lina Mu
Jinkou Zhao
Jian-Yu Rao
Qing-Yi Lu
Zuo-Feng Zhang
Publication date
01-10-2013
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 10/2013
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-013-2770-2

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