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Published in: Medical Oncology 3/2013

01-09-2013 | Original Paper

Genetic analysis of ADIPOQ variants and gastric cancer risk: a hospital-based case–control study in China

Authors: Lei Ye, Zuo-Yang Zhang, Wei-Dong Du, Marion E. Schneider, Yue Qiu, Yuan Zhou, Fu-Sheng Zhou, Xian-Bo Zuo, Gang Chen, Xue-Ling Ma, Hong-Zhen Xia, Song Xu, Ji-Feng Wu, Hong-Yuan Xu, Xue-Jun Zhang

Published in: Medical Oncology | Issue 3/2013

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Abstract

Single-nucleotide polymorphisms (SNPs) of adiponectin (ADIPOQ), adiponectin receptor 1 (ADIPOR1) and ADIPOR2 genes contribute to the risk and progression of cancers. Here, we investigated the associations between variants of these three genes and the risk of gastric cancer. We genotyped six ADIPOQ SNPs, nine ADIPOR1 SNPs and six ADIPOR2 SNPs using the Sequenom technique in a hospital-based case–control study of patients with gastric cancer and cancer-free controls in the Chinese Han population. We found associations of certain variants with location of gastric cancer. Rs16861205 with the minor allele A in ADIPOQ, rs10773989 with the minor allele C and rs1044471 with the minor allele T in ADIPOR2 presented significant associations with a decreased risk of cardia cancer (P = 0.024, OR 0.605, 95 % CI 0.390–0.938; P = 0.015, OR 0.699, 95 % CI 0.522–0.935; and P = 0.022, OR = 0.703, 95 % CI 0.519–0.951, respectively). ADIPOQ rs16861205 with minor allele A displayed an association with an increased risk of body cancer (P = 0.010, OR 1.821, 95 % CI 1.148–2.890). Further stratified analysis of the patients indicated that there were significant correlations for rs1342387A/G (P = 0.027) and rs16861205A/G (P = 0.000) with tumor location; rs16850799A/G (P = 0.004) and rs2058033C/A (P = 0.003) with invasion depth; rs16850799A/G (P = 0.019) with the tumor-node-metastasis stage; rs16850799A/G (P = 0.016), rs1501299A/C (P = 0.005) and rs1063538C/T (P = 0.017) with alcohol consumption; rs11612414A/G (P = 0.040) and rs12733285T/C (P = 0.005) with salted food; rs1063538C/T (P = 0.043) with family history of gastric cancer; and rs11612414A/G (P = 0.029) with gender. Adiponectin expression significantly correlated with gender (P = 0.014), alcohol consumption (P = 0.037), family history (P = 0.019) and invasion depth of primary tumor (P = 0.024). Our data suggested that variants of ADIPOQ may be genetic markers conferring susceptibility to gastric cancer subtypes. These findings need to be validated in a larger panel of samples from distinct populations.
Literature
1.
go back to reference Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.PubMedCrossRef Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.PubMedCrossRef
2.
go back to reference Wex T, Bornschein J, Malfertheiner P. Host polymorphisms of immune regulatory genes as risk factors for gastric cancer. Minerva Gastroenterol Dietol. 2009;55(4):395–408.PubMed Wex T, Bornschein J, Malfertheiner P. Host polymorphisms of immune regulatory genes as risk factors for gastric cancer. Minerva Gastroenterol Dietol. 2009;55(4):395–408.PubMed
3.
go back to reference Barresi V, Grosso M, Giuffre G, Tuccari G, Barresi G. The expression of adiponectin receptors Adipo-R1 and Adipo-R2 is associated with an intestinal histotype and longer survival in gastric carcinoma. J Clin Pathol. 2009;62(8):705–9. doi:10.1136/jcp.2009.066175.PubMedCrossRef Barresi V, Grosso M, Giuffre G, Tuccari G, Barresi G. The expression of adiponectin receptors Adipo-R1 and Adipo-R2 is associated with an intestinal histotype and longer survival in gastric carcinoma. J Clin Pathol. 2009;62(8):705–9. doi:10.​1136/​jcp.​2009.​066175.PubMedCrossRef
6.
go back to reference Korner A, Pazaitou-Panayiotou K, Kelesidis T, Kelesidis I, Williams CJ, Kaprara A, et al. Total and high-molecular-weight adiponectin in breast cancer: in vitro and in vivo studies. J Clin Endocrinol Metab. 2007;92(3):1041–8. doi:10.1210/jc.2006-1858.PubMedCrossRef Korner A, Pazaitou-Panayiotou K, Kelesidis T, Kelesidis I, Williams CJ, Kaprara A, et al. Total and high-molecular-weight adiponectin in breast cancer: in vitro and in vivo studies. J Clin Endocrinol Metab. 2007;92(3):1041–8. doi:10.​1210/​jc.​2006-1858.PubMedCrossRef
8.
9.
go back to reference Kim AY, Lee YS, Kim KH, Lee JH, Lee HK, Jang SH, et al. Adiponectin represses colon cancer cell proliferation via AdipoR1- and -R2-mediated AMPK activation. Mol Endocrinol. 2010;24(7):1441–52. doi:10.1210/me.2009-0498.PubMedCrossRef Kim AY, Lee YS, Kim KH, Lee JH, Lee HK, Jang SH, et al. Adiponectin represses colon cancer cell proliferation via AdipoR1- and -R2-mediated AMPK activation. Mol Endocrinol. 2010;24(7):1441–52. doi:10.​1210/​me.​2009-0498.PubMedCrossRef
10.
go back to reference Williams CJ, Mitsiades N, Sozopoulos E, Hsi A, Wolk A, Nifli AP, et al. Adiponectin receptor expression is elevated in colorectal carcinomas but not in gastrointestinal stromal tumors. Endocr Relat Cancer. 2008;15(1):289–99. doi:10.1677/ERC-07-0197.PubMedCrossRef Williams CJ, Mitsiades N, Sozopoulos E, Hsi A, Wolk A, Nifli AP, et al. Adiponectin receptor expression is elevated in colorectal carcinomas but not in gastrointestinal stromal tumors. Endocr Relat Cancer. 2008;15(1):289–99. doi:10.​1677/​ERC-07-0197.PubMedCrossRef
11.
go back to reference Dalamaga M, Migdalis I, Fargnoli JL, Papadavid E, Bloom E, Mitsiades N, et al. Pancreatic cancer expresses adiponectin receptors and is associated with hypoleptinemia and hyperadiponectinemia: a case–control study. Cancer Causes Control. 2009;20(5):625–33. doi:10.1007/s10552-008-9273-z.PubMedCrossRef Dalamaga M, Migdalis I, Fargnoli JL, Papadavid E, Bloom E, Mitsiades N, et al. Pancreatic cancer expresses adiponectin receptors and is associated with hypoleptinemia and hyperadiponectinemia: a case–control study. Cancer Causes Control. 2009;20(5):625–33. doi:10.​1007/​s10552-008-9273-z.PubMedCrossRef
15.
go back to reference Macis D, Gandini S, Guerrieri-Gonzaga A, Johansson H, Magni P, Ruscica M, et al. Prognostic effect of circulating adiponectin in a randomized 2 × 2 trial of low-dose tamoxifen and fenretinide in premenopausal women at risk for breast cancer. J Clin Oncol. 2012;30(2):151–7. doi:10.1200/JCO.2011.35.2237.PubMedCrossRef Macis D, Gandini S, Guerrieri-Gonzaga A, Johansson H, Magni P, Ruscica M, et al. Prognostic effect of circulating adiponectin in a randomized 2 × 2 trial of low-dose tamoxifen and fenretinide in premenopausal women at risk for breast cancer. J Clin Oncol. 2012;30(2):151–7. doi:10.​1200/​JCO.​2011.​35.​2237.PubMedCrossRef
16.
go back to reference Dal Maso L, Augustin LS, Karalis A, Talamini R, Franceschi S, Trichopoulos D, et al. Circulating adiponectin and endometrial cancer risk. J Clin Endocrinol Metab. 2004;89(3):1160–3.PubMedCrossRef Dal Maso L, Augustin LS, Karalis A, Talamini R, Franceschi S, Trichopoulos D, et al. Circulating adiponectin and endometrial cancer risk. J Clin Endocrinol Metab. 2004;89(3):1160–3.PubMedCrossRef
17.
18.
go back to reference Chen MW, Ye S, Zhao LL, Wang SY, Li YX, Yu CJ, et al. Association of plasma total and high-molecular-weight adiponectin with risk of colorectal cancer: an observational study in Chinese male. Med Oncol. 2012;. doi:10.1007/s12032-012-0280-2. Chen MW, Ye S, Zhao LL, Wang SY, Li YX, Yu CJ, et al. Association of plasma total and high-molecular-weight adiponectin with risk of colorectal cancer: an observational study in Chinese male. Med Oncol. 2012;. doi:10.​1007/​s12032-012-0280-2.
19.
go back to reference Ishikawa M, Kitayama J, Kazama S, Hiramatsu T, Hatano K, Nagawa H. Plasma adiponectin and gastric cancer. Clin Cancer Res. 2005;11(2 Pt 1):466–72.PubMed Ishikawa M, Kitayama J, Kazama S, Hiramatsu T, Hatano K, Nagawa H. Plasma adiponectin and gastric cancer. Clin Cancer Res. 2005;11(2 Pt 1):466–72.PubMed
23.
go back to reference Cui E, Deng A, Wang X, Wang B, Mao W, Feng X, et al. The role of adiponectin (ADIPOQ) gene polymorphisms in the susceptibility and prognosis of non-small cell lung cancer. Biochem Cell Biol. 2011;89(3):308–13. doi:10.1139/O11-005.PubMedCrossRef Cui E, Deng A, Wang X, Wang B, Mao W, Feng X, et al. The role of adiponectin (ADIPOQ) gene polymorphisms in the susceptibility and prognosis of non-small cell lung cancer. Biochem Cell Biol. 2011;89(3):308–13. doi:10.​1139/​O11-005.PubMedCrossRef
25.
go back to reference Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81(3):559–75. doi:10.1086/519795.PubMedCrossRef Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81(3):559–75. doi:10.​1086/​519795.PubMedCrossRef
27.
go back to reference He B, Pan Y, Zhang Y, Bao Q, Chen L, Nie Z, et al. Effects of genetic variations in the adiponectin pathway genes on the risk of colorectal cancer in the Chinese population. BMC Med Genet. 2011;12:94. doi:10.1186/1471-2350-12-94.PubMedCrossRef He B, Pan Y, Zhang Y, Bao Q, Chen L, Nie Z, et al. Effects of genetic variations in the adiponectin pathway genes on the risk of colorectal cancer in the Chinese population. BMC Med Genet. 2011;12:94. doi:10.​1186/​1471-2350-12-94.PubMedCrossRef
28.
go back to reference Carvajal-Carmona LG, Spain S, Kerr D, Houlston R, Cazier JB, Tomlinson I. Common variation at the adiponectin locus is not associated with colorectal cancer risk in the UK. Hum Mol Genet. 2009;18(10):1889–92. doi:10.1093/hmg/ddp109.PubMedCrossRef Carvajal-Carmona LG, Spain S, Kerr D, Houlston R, Cazier JB, Tomlinson I. Common variation at the adiponectin locus is not associated with colorectal cancer risk in the UK. Hum Mol Genet. 2009;18(10):1889–92. doi:10.​1093/​hmg/​ddp109.PubMedCrossRef
30.
go back to reference Shi Y, Hu Z, Wu C, Dai J, Li H, Dong J, et al. A genome-wide association study identifies new susceptibility loci for non-cardia gastric cancer at 3q13.31 and 5p13.1. Nat Genet. 2011;43(12):1215–8. doi:10.1038/ng.978.PubMedCrossRef Shi Y, Hu Z, Wu C, Dai J, Li H, Dong J, et al. A genome-wide association study identifies new susceptibility loci for non-cardia gastric cancer at 3q13.31 and 5p13.1. Nat Genet. 2011;43(12):1215–8. doi:10.​1038/​ng.​978.PubMedCrossRef
33.
go back to reference Kang JH, Yu BY, Youn DS. Relationship of serum adiponectin and resistin levels with breast cancer risk. J Korean Med Sci. 2007;22(1):117–21.PubMedCrossRef Kang JH, Yu BY, Youn DS. Relationship of serum adiponectin and resistin levels with breast cancer risk. J Korean Med Sci. 2007;22(1):117–21.PubMedCrossRef
34.
go back to reference Brakenhielm E, Veitonmaki N, Cao R, Kihara S, Matsuzawa Y, Zhivotovsky B, et al. Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci USA. 2004;101(8):2476–81.PubMedCrossRef Brakenhielm E, Veitonmaki N, Cao R, Kihara S, Matsuzawa Y, Zhivotovsky B, et al. Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci USA. 2004;101(8):2476–81.PubMedCrossRef
35.
go back to reference Yamamoto N, Oshima T, Yoshihara K, Sato T, Yamada R, Fujii S, et al. Reduced expression of the AdipoR1 gene is correlated with venous invasion in colorectal cancer. Mol Med Report. 2009;2(4):555–9. doi:10.3892/mmr_00000136.CrossRef Yamamoto N, Oshima T, Yoshihara K, Sato T, Yamada R, Fujii S, et al. Reduced expression of the AdipoR1 gene is correlated with venous invasion in colorectal cancer. Mol Med Report. 2009;2(4):555–9. doi:10.​3892/​mmr_​00000136.CrossRef
36.
40.
go back to reference Xu A, Chan KW, Hoo RL, Wang Y, Tan KC, Zhang J, et al. Testosterone selectively reduces the high molecular weight form of adiponectin by inhibiting its secretion from adipocytes. J Biol Chem. 2005;280(18):18073–80. doi:10.1074/jbc.M414231200.PubMedCrossRef Xu A, Chan KW, Hoo RL, Wang Y, Tan KC, Zhang J, et al. Testosterone selectively reduces the high molecular weight form of adiponectin by inhibiting its secretion from adipocytes. J Biol Chem. 2005;280(18):18073–80. doi:10.​1074/​jbc.​M414231200.PubMedCrossRef
Metadata
Title
Genetic analysis of ADIPOQ variants and gastric cancer risk: a hospital-based case–control study in China
Authors
Lei Ye
Zuo-Yang Zhang
Wei-Dong Du
Marion E. Schneider
Yue Qiu
Yuan Zhou
Fu-Sheng Zhou
Xian-Bo Zuo
Gang Chen
Xue-Ling Ma
Hong-Zhen Xia
Song Xu
Ji-Feng Wu
Hong-Yuan Xu
Xue-Jun Zhang
Publication date
01-09-2013
Publisher
Springer US
Published in
Medical Oncology / Issue 3/2013
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-013-0658-9

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