Advertisement

Tumor Biology

, Volume 36, Issue 2, pp 585–594 | Cite as

Causal relevance of circulating adiponectin with cancer: a meta-analysis implementing Mendelian randomization

  • Yuan Pei
  • Yue Xu
  • Wenquan Niu
Research Article

Abstract

Some studies have observed a lower circulating level of adiponectin in cancer patients, but whether this observation is causal remains unresolved. We therefore undertook a meta-analysis implementing Mendelian randomization to exploit the causal relevance of circulating adiponectin with cancer by using multiple polymorphisms in adiponectin encoded gene ADIPOQ as instrumental variables. Eligible articles were identified from PubMed and Embase. Data and study quality were assessed in duplicate. Total 26 articles including 31 study groups were analyzed. Overall allelic association with cancer was significant for rs822396 (odds ratio (OR) = 0.91; P = 0.045) and rs1501299 (OR = 0.89; P = 0.051), with low or moderate heterogeneity. Carriers of rs2241766 GG genotype (weighted mean difference (WMD) = 0.86; P = 0.037) or G allele (WMD = 0.68; P = 0.047) had significantly higher circulating adiponectin than the TT genotype carriers, without heterogeneity. Using rs2241766 as an instrument in Mendelian randomization analysis, an increment of 1 mg/L in circulating adiponectin was significantly associated with a 43–50 % reduced risk for lung cancer, but with a 20–40 % increased risk of colorectal cancer, respectively. There was no observable publication bias. Genetically elevated circulating adiponectin might confer a protective effect against lung cancer, yet a risky effect for colorectal cancer. Further validation is urgently required.

Keywords

Adiponectin Cancer Polymorphism Meta-analysis Mendelian randomization 

Notes

Conflicts of interest

None

Supplementary material

13277_2014_2654_MOESM1_ESM.doc (64 kb)
ESM 1 (DOC 64 kb)

References

  1. 1.
    Dalamaga M, Diakopoulos KN, Mantzoros CS. The role of adiponectin in cancer: a review of current evidence. Endocr Rev. 2012;33:547–94.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Hebbard L, Ranscht B. Multifaceted roles of adiponectin in cancer. Best Pract Res Clin Endocrinol Metab. 2014;28:59–69.CrossRefPubMedGoogle Scholar
  3. 3.
    Smith GD, Ebrahim S. Mendelian randomization: prospects, potentials, and limitations. Int J Epidemiol. 2004;33:30–42.CrossRefPubMedGoogle Scholar
  4. 4.
    Al-Harithy RN, Al-Zahrani MH. The adiponectin gene, ADIPOQ, and genetic susceptibility to colon cancer. Oncol Lett. 2012;3:176–80.PubMedGoogle Scholar
  5. 5.
    Dastani Z, Hivert MF, Timpson N, Perry JR, Yuan X, Scott RA, et al. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. PLoS Genet. 2012;8:e1002607.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Bowden J, Tierney JF, Copas AJ, Burdett S. Quantifying, displaying and accounting for heterogeneity in the meta-analysis of RCTs using standard and generalised Q statistics. BMC Med Res Methodol. 2011;11:41.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Doecke JD, Zhao ZZ, Stark MS, Green AC, Hayward NK, Montgomery GW, et al. Single nucleotide polymorphisms in obesity-related genes and the risk of esophageal cancers. Cancer Epidemiol Biomarkers Prev. 2008;17:1007–12.CrossRefPubMedGoogle Scholar
  10. 10.
    Kaklamani VG, Sadim M, Hsi A, Offit K, Oddoux C, Ostrer H, et al. Variants of the adiponectin and adiponectin receptor 1 genes and breast cancer risk. Cancer Res. 2008;68:3178–84.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Kaklamani VG, Wisinski KB, Sadim M, Gulden C, Do A, Offit K, et al. Variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes and colorectal cancer risk. JAMA. 2008;300:1523–31.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Wong VW, Wong GL, Tsang SW, Hui AY, Chan AW, Choi PC, et al. Genetic polymorphisms of adiponectin and tumor necrosis factor-alpha and nonalcoholic fatty liver disease in Chinese people. J Gastroenterol Hepatol. 2008;23:914–21.CrossRefPubMedGoogle Scholar
  13. 13.
    Moore SC, Leitzmann MF, Albanes D, Weinstein SJ, Snyder K, Virtamo J, et al. Adipokine genes and prostate cancer risk. Int J Cancer. 2009;124:869–76.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Pechlivanis S, Bermejo JL, Pardini B, Naccarati A, Vodickova L, Novotny J, et al. Genetic variation in adipokine genes and risk of colorectal cancer. Euro J Endocrinol. 2009;160:933–40.CrossRefGoogle Scholar
  15. 15.
    Teras LR, Goodman M, Patel AV, Bouzyk M, Tang W, Diver WR, et al. No association between polymorphisms in LEP, LEPR, ADIPOQ, ADIPOR1, or ADIPOR2 and postmenopausal breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2009;18:2553–7.CrossRefPubMedGoogle Scholar
  16. 16.
    Tsilidis KK, Helzlsouer KJ, Smith MW, Grinberg V, Hoffman-Bolton J, Clipp SL, et al. Association of common polymorphisms in IL10, and in other genes related to inflammatory response and obesity with colorectal cancer. Cancer Causes Control. 2009;20:1739–51.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Wang MH, Helzlsouer KJ, Smith MW, Hoffman-Bolton JA, Clipp SL, Grinberg V, et al. Association of IL10 and other immune response- and obesity-related genes with prostate cancer in CLUE II. Prostate. 2009;69:874–85.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Beebe-Dimmer JL, Zuhlke KA, Ray AM, Lange EM, Cooney KA. Genetic variation in adiponectin (ADIPOQ) and the type 1 receptor (ADIPOR1), obesity and prostate cancer in African Americans. Prostate Cancer Prostatic Dis. 2010;13:362–8.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Partida-Perez M, de la Ayala-Madrigal LM, Peregrina-Sandoval J, Macias-Gomez N, Moreno-Ortiz J, Leal-Ugarte E, et al. Association of LEP and ADIPOQ common variants with colorectal cancer in Mexican patients. Cancer Biomark. 2010;7:117–21.CrossRefPubMedGoogle Scholar
  20. 20.
    Al Khaldi RM, Al Mulla F, Al Awadhi S, Kapila K, Mojiminiyi OA. Associations of single nucleotide polymorphisms in the adiponectin gene with adiponectin levels and cardio-metabolic risk factors in patients with cancer. Dis Markers. 2011;30:197–212.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    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;89:308–13.CrossRefPubMedGoogle Scholar
  22. 22.
    Dhillon PK, Penney KL, Schumacher F, Rider JR, Sesso HD, Pollak M, et al. Common polymorphisms in the adiponectin and its receptor genes, adiponectin levels and the risk of prostate cancer. Cancer Epidemiol Biomarkers Prev. 2011;20:2618–27.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Gornick MC, Rennert G, Moreno V, Gruber SB. Adiponectin gene and risk of colorectal cancer. Br J Cancer. 2011;105:562–4.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Kaklamani V, Yi N, Zhang K, Sadim M, Offit K, Oddoux C, et al. Polymorphisms of ADIPOQ and ADIPOR1 and prostate cancer risk. Metab Clin Exp. 2011;60:1234–43.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Tang H, Dong X, Hassan M, Abbruzzese JL, Li D. Body mass index and obesity- and diabetes-associated genotypes and risk for pancreatic cancer. Cancer Epidemiol Biomarkers Prev. 2011;20:779–92.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Keku TO, Vidal A, Oliver S, Hoyo C, Hall IJ, Omofoye O, et al. Genetic variants in IGF-I, IGF-II, IGFBP-3, and adiponectin genes and colon cancer risk in African Americans and Whites. Cancer Causes Control. 2012;23:1127–38.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Chornokur G, Amankwah EK, Davis SN, Phelan CM, Park JY, Pow-Sang J, et al. Variation in HNF1B and obesity may influence prostate cancer risk in African American men: a pilot study. Prostate Cancer. 2013;2013:384594.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Hu X, Yuan P, Yan J, Feng F, Li X, Liu W, et al. Gene polymorphisms of +45 T>G, −866 G>A, and Ala54Thr on the risk of colorectal cancer: a matched case-control study. PLoS One. 2013;8:e67275.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Kaklamani VG, Hoffmann TJ, Thornton TA, Hayes G, Chlebowski R, Van Horn L, et al. Adiponectin pathway polymorphisms and risk of breast cancer in African Americans and Hispanics in the Women’s Health Initiative. Breast Cancer Res Treat. 2013;139:461–8.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Ye L, Zhang ZY, Du WD, Schneider ME, Qiu Y, Zhou Y, et al. Genetic analysis of ADIPOQ variants and gastric cancer risk: a hospital-based case-control study in china. Med Oncol. 2013;30:658.CrossRefPubMedGoogle Scholar
  32. 32.
    Cai X, Gan Y, Fan Y, Hu J, Jin Y, Chen F, et al. The adiponectin gene single-nucleotide polymorphism rs1501299 is associated with hepatocellular carcinoma risk. Clin Translational Oncol. 2014;16:166–72.CrossRefGoogle Scholar
  33. 33.
    Llanos AA, Brasky TM, Mathew J, Makambi KH, Marian C, Dumitrescu RG, Freudenheim JL, Shields PG. Genetic variation in adipokine genes and associations with adiponectin and leptin concentrations in plasma and breast tissues. Cancer Epidemiol Biomarkers Prev. 2014;23(8):1559–68. doi: 10.1158/1055-9965.
  34. 34.
    Li Q, Ma Y, Sang W, Cui W, Li X, Liu X, et al. Five common haplotype-tagging variants of adiponectin (ADIPOQ) and cancer susceptibility: a meta-analysis. Genet Test Mol Biomarkers. 2014;18:417–24.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Zhou W, Liu Y, Zhong DW. Adiponectin (ADIPOQ) rs2241766 G/T polymorphism is associated with risk of cancer: evidence from a meta-analysis. Tumour Biol. 2013;34:493–504.CrossRefPubMedGoogle Scholar
  36. 36.
    Ye C, Wang J, Tan S, Zhang J, Li M, Sun P. Meta-analysis of adiponectin polymorphisms and colorectal cancer risk. Int J Med Sci. 2013;10:1113–20.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Yang Y, Zhang F, Ding R, Skrip L, Wang Y, Lei H, et al. ADIPOQ gene polymorphisms and cancer risk: a meta-analysis. Cytokine. 2013;61:565–71.CrossRefPubMedGoogle Scholar
  38. 38.
    Fan HJ, Wen ZF, Xu BL, Wu JJ, Jia YX, Gao M, et al. Three adiponectin rs1501299G/T, rs822395A/C, and rs822396A/G polymorphisms and risk of cancer development: a meta-analysis. Tumour Biol. 2013;34:769–78.CrossRefPubMedGoogle Scholar
  39. 39.
    Ye J, Jia J, Dong S, Zhang C, Yu S, Li L, et al. Circulating adiponectin levels and the risk of breast cancer: a meta-analysis. Eur J Cancer Prev. 2014;23:158–65.CrossRefPubMedGoogle Scholar
  40. 40.
    Macis D, Guerrieri-Gonzaga A, Gandini S. Circulating adiponectin and breast cancer risk: a systematic review and meta-analysis. Int J Epidemiol. 2014;43(4):1226–36. doi: 10.1093/ije/dyu088.
  41. 41.
    Liu LY, Wang M, Ma ZB, Yu LX, Zhang Q, Gao DZ, et al. The role of adiponectin in breast cancer: a meta-analysis. PLoS One. 2013;8:e73183.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    An W, Bai Y, Deng SX, Gao J, Ben QW, Cai QC, et al. Adiponectin levels in patients with colorectal cancer and adenoma: a meta-analysis. Eur J Cancer Prev. 2012;21:126–33.CrossRefPubMedGoogle Scholar
  43. 43.
    Xu XT, Xu Q, Tong JL, Zhu MM, Huang ML, Ran ZH, et al. Meta-analysis: circulating adiponectin levels and risk of colorectal cancer and adenoma. J Dig Dis. 2011;12:234–44.CrossRefPubMedGoogle Scholar
  44. 44.
    Vanderweele TJ, Tchetgen Tchetgen EJ, Cornelis M, Kraft P. Methodological challenges in Mendelian randomization. Epidemiology. 2014;25:427–35.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Goktas S, Yilmaz MI, Caglar K, Sonmez A, Kilic S, Bedir S. Prostate cancer and adiponectin. Urology. 2005;65:1168–72.CrossRefPubMedGoogle Scholar
  46. 46.
    Ishikawa M, Kitayama J, Kazama S, Hiramatsu T, Hatano K, Nagawa H. Plasma adiponectin and gastric cancer. Clin Cancer Res. 2005;11:466–72.CrossRefPubMedGoogle Scholar
  47. 47.
    Bianchini F, Kaaks R, Vainio H. Overweight, obesity, and cancer risk. Lancet Oncol. 2002;3:565–74.CrossRefPubMedGoogle Scholar
  48. 48.
    Chen DC, Chung YF, Yeh YT, Chaung HC, Kuo FC, Fu OY, et al. Serum adiponectin and leptin levels in Taiwanese breast cancer patients. Cancer Lett. 2006;237:109–14.CrossRefPubMedGoogle Scholar
  49. 49.
    Petridou E, Mantzoros C, Dessypris N, Koukoulomatis P, Addy C, Voulgaris Z, et al. Plasma adiponectin concentrations in relation to endometrial cancer: a case-control study in Greece. J Clin Endocrinol Metab. 2003;88:993–7.CrossRefPubMedGoogle Scholar
  50. 50.
    Cardon LR, Bell JI. Association study designs for complex diseases. Nat Rev Genet. 2001;2:91–9.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of Stomatology, Huashan HospitalFudan UniversityShanghaiChina
  2. 2.State Key Laboratory of Medical Genomics, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina

Personalised recommendations