Skip to main content
SpringerLink
Log in

Association of variants on ADIPOQ and AdipoR1 and the prognosis of gastric cancer patients after gastrectomy treatment

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Adiponectin is a protein hormone secreted exclusively by adipocytes and it is responsible for insulin sensitization in the human body. Deregulation of adiponectin and its downstream signaling pathway genes have been found to be involved in the gastric cancer carcinogenesis; however, whether the variants on adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) affect the prognosis of gastric cancer patients are still unknown. Here we have recruited 455 gastric cancer patients, who have received the gastrectomy treatment to evaluate the prognostic effects of variants on ADIPOQ (rs266729 and rs822395) and AdipoR1 (rs12733285 and rs1342387) for the gastric cancer patients. No significant association between the four variants and the overall survival of the gastric cancer patients was found. However, for those patients without a previous history of alcohol drinking, the rs266729 GG/CG genotype carriers showed a significantly decreased gastric cancer mortality compared to homogeneity CC patients (HR 0.74, 95 % CI 0.56–0.97; p = 0.032) after adjustment for variants age, sex, smoking status, tumor stage, tumor location and post-surgery chemotherapy. No significant association between the variant rs266729 genotypes and overall survival for the gastric cancer patients with an alcohol drinking habit. These data suggested that the variant rs266729 was an independent prognostic factor for the never drinking gastric cancer patients who received surgical treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

SNP:

Single nucleotide polymorphisms

ADIPOQ:

Adiponectin gene

ADIPOR1:

Adiponectin receptor 1 gene

HR:

Hazard ratio

95 % CI:

95 % confidence interval

AMPK:

AMP-activated protein kinase

PPAR:

Peroxisome proliferator-activated receptor

NSCLC:

Non-small cell lung cancer

FGF:

Fibroblast growth factor

PDGF-BB:

Platelet-derived growth factor BB

HB EGF:

Heparin-binding epidermal growth factor-like growth factor

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E et al (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  2. Ding YB, Xia TS, Wu JD, Chen GY, Wang S et al (2012) Surgical outcomes for gastric cancer of a single institute in southeast China. Am J Surg 203:217–221

    Article  PubMed  Google Scholar 

  3. Diez JJ, Iglesias P (2010) The role of the novel adipocyte-derived protein adiponectin in human disease: an update. Mini Rev Med Chem 10:856–869

    Article  CAS  PubMed  Google Scholar 

  4. Diez JJ, Iglesias P (2003) The role of the novel adipocyte-derived hormone adiponectin in human disease. Eur J Endocrinol 148:293–300

    Article  CAS  PubMed  Google Scholar 

  5. An W, Bai Y, Deng SX, Gao J, Ben QW et al (2011) Adiponectin levels in patients with colorectal cancer and adenoma: a meta-analysis. Eur J Cancer Prev 21(2):126–133

    Article  Google Scholar 

  6. Miyoshi Y, Funahashi T, Kihara S, Taguchi T, Tamaki Y et al (2003) Association of serum adiponectin levels with breast cancer risk. Clin Cancer Res 9:5699–5704

    CAS  PubMed  Google Scholar 

  7. Chen DC, Chung YF, Yeh YT, Chaung HC, Kuo FC et al (2006) Serum adiponectin and leptin levels in Taiwanese breast cancer patients. Cancer Lett 237:109–114

    Article  CAS  PubMed  Google Scholar 

  8. Tworoger SS, Eliassen AH, Kelesidis T, Colditz GA, Willett WC et al (2007) Plasma adiponectin concentrations and risk of incident breast cancer. J Clin Endocrinol Metab 92:1510–1516

    Article  CAS  PubMed  Google Scholar 

  9. Dal Maso L, Augustin LS, Karalis A, Talamini R, Franceschi S et al (2004) Circulating adiponectin and endometrial cancer risk. J Clin Endocrinol Metab 89:1160–1163

    Article  CAS  PubMed  Google Scholar 

  10. Soliman PT, Wu D, Tortolero-Luna G, Schmeler KM, Slomovitz BM et al (2006) Association between adiponectin, insulin resistance, and endometrial cancer. Cancer 106:2376–2381

    Article  CAS  PubMed  Google Scholar 

  11. Ashizawa N, Yahata T, Quan J, Adachi S, Yoshihara K et al (2010) Serum leptin–adiponectin ratio and endometrial cancer risk in postmenopausal female subjects. Gynecol Oncol 119:65–69

    Article  CAS  PubMed  Google Scholar 

  12. Arisan ED, Arisan S, Atis G, Palavan-Unsal N, Ergenekon E (2009) Serum adipocytokine levels in prostate cancer patients. Urol Int 82:203–208

    Article  CAS  PubMed  Google Scholar 

  13. Li H, Stampfer MJ, Mucci L, Rifai N, Qiu W et al (2010) A 25-year prospective study of plasma adiponectin and leptin concentrations and prostate cancer risk and survival. Clin Chem 56:34–43

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Ferroni P, Palmirotta R, Spila A, Martini F, Raparelli V et al (2007) Prognostic significance of adiponectin levels in non-metastatic colorectal cancer. Anticancer Res 27:483–489

    CAS  PubMed  Google Scholar 

  15. Duggan C, Irwin ML, Xiao L, Henderson KD, Smith AW et al (2011) Associations of insulin resistance and adiponectin with mortality in women with breast cancer. J Clin Oncol 29:32–39

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T et al (2003) Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423:762–769

    Article  CAS  PubMed  Google Scholar 

  17. Williams CJ, Mitsiades N, Sozopoulos E, Hsi A, Wolk A et al (2008) Adiponectin receptor expression is elevated in colorectal carcinomas but not in gastrointestinal stromal tumors. Endocr Relat Cancer 15:289–299

    Article  CAS  PubMed  Google Scholar 

  18. Tsukada T, Fushida S, Harada S, Terai S, Yagi Y et al (2011) Adiponectin receptor-1 expression is associated with good prognosis in gastric cancer. J Exp Clin Cancer Res 30:107

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Petridou ET, Mitsiades N, Gialamas S, Angelopoulos M, Skalkidou A et al (2007) Circulating adiponectin levels and expression of adiponectin receptors in relation to lung cancer: two case-control studies. Oncology 73:261–269

    Article  CAS  PubMed  Google Scholar 

  20. Dalamaga M, Migdalis I, Fargnoli JL, Papadavid E, Bloom E et al (2009) Pancreatic cancer expresses adiponectin receptors and is associated with hypoleptinemia and hyperadiponectinemia: a case-control study. Cancer Causes Control 20:625–633

    Article  PubMed Central  PubMed  Google Scholar 

  21. Michalakis K, Williams CJ, Mitsiades N, Blakeman J, Balafouta-Tselenis S et al (2007) Serum adiponectin concentrations and tissue expression of adiponectin receptors are reduced in patients with prostate cancer: a case control study. Cancer Epidemiol Biomark Prev 16:308–313

    Article  CAS  Google Scholar 

  22. Yamauchi T, Nio Y, Maki T, Kobayashi M, Takazawa T et al (2007) Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med 13:332–339

    Article  CAS  PubMed  Google Scholar 

  23. Ishikawa M, Kitayama J, Kazama S, Hiramatsu T, Hatano K et al (2005) Plasma adiponectin and gastric cancer. Clin Cancer Res 11:466–472

    Article  CAS  PubMed  Google Scholar 

  24. Seker M, Bilici A, Sonmez B, Ustaalioglu BB, Gumus M et al (2010) The association of serum adiponectin levels with histopathological variables in gastric cancer patients. Med Oncol 27:1319–1323

    Article  CAS  PubMed  Google Scholar 

  25. Ishikawa M, Kitayama J, Yamauchi T, Kadowaki T, Maki T et al (2007) Adiponectin inhibits the growth and peritoneal metastasis of gastric cancer through its specific membrane receptors AdipoR1 and AdipoR2. Cancer Sci 98:1120–1127

    Article  CAS  PubMed  Google Scholar 

  26. Otani K, Kitayama J, Kamei T, Soma D, Miyato H et al (2010) Adiponectin receptors are downregulated in human gastric cancer. J Gastroenterol 45:918–927

    Article  CAS  PubMed  Google Scholar 

  27. Cui E, Deng A, Wang X, Wang B, Mao W et al (2011) The role of adiponectin (ADIPOQ) gene polymorphisms in the susceptibility and prognosis of non-small cell lung cancer. Biochem Cell Biol 89:308–313

    Article  CAS  PubMed  Google Scholar 

  28. Wang Y, Lam KS, Xu JY, Lu G, Xu LY et al (2005) Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization-dependent manner. J Biol Chem 280:18341–18347

    Article  CAS  PubMed  Google Scholar 

  29. Kim AY, Lee YS, Kim KH, Lee JH, Lee HK et al (2010) Adiponectin represses colon cancer cell proliferation via AdipoR1- and -R2-mediated AMPK activation. Mol Endocrinol 24:1441–1452

    Article  CAS  PubMed  Google Scholar 

  30. Taliaferro-Smith L, Nagalingam A, Zhong D, Zhou W, Saxena NK et al (2009) LKB1 is required for adiponectin-mediated modulation of AMPK-S6K axis and inhibition of migration and invasion of breast cancer cells. Oncogene 28:2621–2633

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Barresi V, Grosso M, Giuffre G, Tuccari G, Barresi G (2009) 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 62:705–709

    Article  CAS  PubMed  Google Scholar 

  32. Laumen H, Saningong AD, Heid IM, Hess J, Herder C et al (2009) Functional characterization of promoter variants of the adiponectin gene complemented by epidemiological data. Diabetes 58:984–991

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Ong KL, Li M, Tso AW, Xu A, Cherny SS et al (2010) Association of genetic variants in the adiponectin gene with adiponectin level and hypertension in Hong Kong Chinese. Eur J Endocrinol 163:251–257

    Article  CAS  PubMed  Google Scholar 

  34. Persson J, Lindberg K, Gustafsson TP, Eriksson P, Paulsson-Berne G et al (2010) Low plasma adiponectin concentration is associated with myocardial infarction in young individuals. J Intern Med 268:194–205

    Article  CAS  PubMed  Google Scholar 

  35. Han LY, Wu QH, Jiao ML, Hao YH, Liang LB et al (2011) Associations between single-nucleotide polymorphisms (+45T > G, +276G > T, −11377C > G, −11391G > A) of adiponectin gene and type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetologia 54:2303–2314

    Article  CAS  PubMed  Google Scholar 

  36. Yamada Y, Kato K, Oguri M, Yoshida T, Yokoi K et al (2008) Association of genetic variants with atherothrombotic cerebral infarction in Japanese individuals with metabolic syndrome. Int J Mol Med 21:801–808

    CAS  PubMed  Google Scholar 

  37. Zhong C, Zhen D, Qi Q, Genshan M (2010) A lack of association between adiponectin polymorphisms and coronary artery disease in a Chinese population. Genet Mol Biol 33:428–433

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Avery PJ, Patel SK, Ibrahim IM, Walker M, Keavney BD (2011) Common variation in the adiponectin gene has an effect on systolic blood pressure. J Hum Hypertens 25:719–724

    Article  CAS  PubMed  Google Scholar 

  39. Kaklamani VG, Wisinski KB, Sadim M, Gulden C, Do A et al (2008) Variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes and colorectal cancer risk. JAMA 300:1523–1531

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Dhillon PK, Penney KL, Schumacher F, Rider JR, Sesso HD et al (2011) Common polymorphisms in the adiponectin and its receptor genes, adiponectin levels and the risk of prostate cancer. Cancer Epidemiol Biomark Prev 20:2618–2627

    Article  CAS  Google Scholar 

  41. Sierksma A, Patel H, Ouchi N, Kihara S, Funahashi T et al (2004) Effect of moderate alcohol consumption on adiponectin, tumor necrosis factor-alpha, and insulin sensitivity. Diabetes Care 27:184–189

    Article  CAS  PubMed  Google Scholar 

  42. Englund Ogge L, Brohall G, Behre CJ, Schmidt C, Fagerberg B (2006) Alcohol consumption in relation to metabolic regulation, inflammation, and adiponectin in 64-year-old Caucasian women: a population-based study with a focus on impaired glucose regulation. Diabetes Care 29:908–913

    Article  PubMed  Google Scholar 

  43. Dal Maso L, La Vecchia C, Augustin LS, Mantzoros CS, Kendall CW et al (2007) Relationship between a wide range of alcohol consumptions, components of the insulin-like growth factor system and adiponectin. Eur J Clin Nutr 61:221–225

    Article  CAS  PubMed  Google Scholar 

  44. Kotani K, Sakane N, Saiga K, Sano Y, Kurozawa Y (2007) Lifestyle-related determinants and serum adiponectin concentrations in a general population of Japanese females. Arch Med Res 38:887–890

    Article  CAS  PubMed  Google Scholar 

  45. Imhof A, Plamper I, Maier S, Trischler G, Koenig W (2009) Effect of drinking on adiponectin in healthy men and women: a randomized intervention study of water, ethanol, red wine, and beer with or without alcohol. Diabetes Care 32:1101–1103

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Joosten MM, Witkamp RF, Hendriks HF (2011) Alterations in total and high-molecular-weight adiponectin after 3 weeks of moderate alcohol consumption in premenopausal women. Metabolism 60:1058–1063

    Article  CAS  PubMed  Google Scholar 

  47. Kawamoto R, Tabara Y, Kohara K, Miki T, Ohtsuka N et al (2010) Alcohol drinking status is associated with serum high molecular weight adiponectin in community-dwelling Japanese men. J Atheroscler Thromb 17:953–962

    Article  CAS  PubMed  Google Scholar 

  48. Nishise Y, Saito T, Makino N, Okumoto K, Ito JI et al (2010) Relationship between alcohol consumption and serum adiponectin levels: the Takahata study–a cross-sectional study of a healthy Japanese population. J Clin Endocrinol Metab 95:3828–3835

    Article  CAS  PubMed  Google Scholar 

  49. Buechler C, Schaffler A, Johann M, Neumeier M, Kohl P et al (2009) Elevated adiponectin serum levels in patients with chronic alcohol abuse rapidly decline during alcohol withdrawal. J Gastroenterol Hepatol 24:558–563

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by grants from the Ministry of Science and Technology of China (2012BAK01B00 and 2014AA020524), the National Nature Science Foundation (81125020, 81328022, 81302507 and 81302809), the Key Research Program KSZD-EW-Z-021 and KSZD-EW-Z-019 of the Chinese Academy of Sciences, the Science and Technology Commission of Shanghai Municipality (12431900500), the Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences(2012KIP308 and 2012KIP515) and the Food Safety Research Center and Key Laboratory of Food Safety Research of INS, SIBS, CAS.

Conflict of interest

None of the authors for the manuscript has declared any conflict of interest.

Author information

Authors and Affiliations

  1. Nantong Tumor Hospital, Nantong, 226000, Jiangsu, People’s Republic of China

    Xuming Wu, Jibin Liu & Fulin Qiang

  2. Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences; School of Life Science and Technology, ShanghaiTech University, Shanghai, 200031, People’s Republic of China

    Peizhan Chen, Chenglin Li & Hui Wang

  3. Key Laboratory of Food Safety Risk Assessment of Ministry of Health, China National Center for Food Safety Risk Assessment, Beijing, 100021, People’s Republic of China

    Hui Wang

  4. Medical Department, the General Hospital of Navy, Beijing, 100037, People’s Republic of China

    Yiyi Ou

Authors
  1. Xuming Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peizhan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yiyi Ou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jibin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chenglin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hui Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fulin Qiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Peizhan Chen, Hui Wang or Fulin Qiang.

Additional information

Xuming Wu, Peizhan Chen, Yiyi Ou and Jibin Liu have contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, X., Chen, P., Ou, Y. et al. Association of variants on ADIPOQ and AdipoR1 and the prognosis of gastric cancer patients after gastrectomy treatment. Mol Biol Rep 42, 355–361 (2015). https://doi.org/10.1007/s11033-014-3775-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-014-3775-4

Keywords

Search

Navigation