Further, we performed a sensitivity analysis by excluding studies in sequence and evaluating the pooled results to investigate the influence of the corresponding study. The variations regarding heterogeneity and direction of the effect were too minor among residual studies to change our results, which, therefore, indicated that the results of our meta-analysis were stable and robust.
In order to investigate the source of heterogeneity, firstly we performed a sensitivity analysis by omitting each study in sequence to investigate the underlying causes. The results showed a minor variation in the test effect, and the excluded studies did not affect the statistical result, indicating the stability of our meta-analysis. Therefore, we identified several characteristics such as ethnicity, menopausal status, study quality, assay methods, ethnicity, and metastasis status to carry out subgroup meta-analysis.
. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015;65:5–29.
. Althuis MD, Dozier JM, Anderson WF, et al. Global trends in breast cancer
incidence and mortality 1973–1997. Int J Epidemiol 2005;34:405–12.
. Keramatinia A, Mousavi-Jarrahi SH, Hiteh M, et al. Trends in incidence of breast cancer
among women under 40 in Asia. Asian Pac J Cancer Prev 2014;15:1387–90.
. Leclère B, Molinié F, Trétarre B, et al. Trends in incidence of breast cancer
among women under 40 in seven European countries: a GRELL cooperative study. Cancer Epidemiol 2013;37:544–9.
. Engin A. Obesity-associated breast cancer
: analysis of risk factors. Adv Exp Med Biol 2017;960:571–606.
. Grossmann ME, Ray A, Nkhata KJ, et al. Obesity and breast cancer
: status of leptin and adiponectin
in pathological processes. Cancer Metastasis Rev 2010;29:641–53.
. Jardé T, Perrier S, Vasson MP, et al. Molecular mechanisms of leptin and adiponectin
in breast cancer
. Eur J Cancer 2011;47:33–43.
. Alokail MS, Al-Daghri N, Abdulkareem A, et al. Metabolic syndrome biomarkers and early breast cancer
in Saudi women: evidence for the presence of a systemic stress response and/or a pre-existing metabolic syndrome-related neoplasia risk? BMC Cancer 2013;13:54.
. Bianchini F, Kaaks R, Vainio H. Overweight, obesity, and cancer risk. Lancet Oncol 2002;3:565–74.
. Housa D, Housová J, Vernerová Z, et al. Adipocytokines and cancer. Physiol Res 2006;55:233–44.
. Kelesidis I, Kelesidis T, Mantzoros CS. Adiponectin
and cancer: a systematic review. Br J Cancer 2006;94:1221–5.
. Miyoshi Y, Funahashi T, Kihara S, et al. Association of serum adiponectin
levels with breast cancer
risk. Clin Cancer Res 2003;9:5699–704.
. Mantzoros C, Petridou E, Dessypris N, et al. Adiponectin
and breast cancer
risk. J Clin Endocrinol Metab 2004;89:1102–7.
. Chen DC, Chung YF, Yeh YT, et al. Serum adiponectin
and leptin levels in Taiwanese breast cancer
patients. Cancer Lett 2006;237:109–14.
. Gulcelik MA, Colakoglu K, Dincer H, et al. Associations between adiponectin
and two different cancers: breast and colon. Asian Pac J Cancer Prev 2012;13:395–8.
. Hou WK, Xu YX, Yu T, et al. Adipocytokines and breast cancer
risk. Chin Med J (Engl) 2007;120:1592–6.
. Liu LY, Wang M, Ma ZB, et al. The role of adiponectin
in breast cancer
: a meta-analysis
. PLoS One 2013;8:e73183.
. Ye J, Jia J, Dong S, et al. Circulating adiponectin
levels and the risk of breast cancer
: a meta-analysis
. Eur J Cancer Prev 2014;23:158–65.
. Macis D, Guerrieri-Gonzaga A, Gandini S. Circulating adiponectin
and breast cancer
risk: a systematic review and meta-analysis
. Int J Epidemiol 2014;43:1226–36.
. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994;50:1088–101.
. Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis
detected by a simple, graphical test. BMJ 1997;315:629–34.
. Jeong YJ, Bong JG, Park SH, et al. Expression of leptin, leptin receptor, adiponectin
, and adiponectin
receptor in ductal carcinoma in situ and invasive breast cancer
. J Breast Cancer
. Karaduman M, Bilici A, Ozet A, et al. Tissue levels of adiponectin
in breast cancer
patients. Med Oncol 2007;24:361–6.
. Lim HY, Im KS, Kim NH, et al. Obesity, expression of adipocytokines, and macrophage infiltration in canine mammary tumors. Vet J 2015;203:326–31.
. Llanos AA, Dumitrescu RG, Marian C, et al. Adipokines in plasma and breast tissues: associations with breast cancer
risk factors. Cancer Epidemiol Biomarkers Prev 2012;21:1745–55.
. Al-Delaimy WK, Flatt SW, Natarajan L, et al. IGF1 and risk of additional breast cancer
in the WHEL study. Endocr Relat Cancer 2011;18:235–44.
. Lee SA, Sung H, Han W, et al. Serum adiponectin
but not leptin at diagnosis as a predictor of breast cancer
survival. Asian Pac J Cancer Prev 2014;15:6137–43.
. George SM, Neuhouser ML, Mayne ST, et al. Postdiagnosis diet quality is inversely related to a biomarker
of inflammation among breast cancer
survivors. Cancer Epidemiol Biomarkers Prev 2010;19:2220–8.
. Beg MS, Saleem S, Turer A, et al. A prospective analysis of plasma adiponectin
and risk of incident cancer: the Dallas Heart Study. J Natl Compr Canc Netw 2015;13:873–8.
. Gaudet MM, Falk RT, Gierach GL, et al. Do adipokines underlie the association between known risk factors and breast cancer
among a cohort of United States women? Cancer Epidemiol 2010;34:580–6.
. Tian YF, Chu CH, Wu MH, et al. Anthropometric measures, plasma adiponectin
, and breast cancer
risk. Endocr Relat Cancer 2007;14:669–77.
. Sonmez B, Seker M, Bilici A, et al. Is there any correlation among adiponectin
levels in serum, tumor tissue and normal tissue of the same patients with breast cancer
? J BUON 2011;16:227–32.
. Ahmed SD, Khanam A, Sultan N, et al. Serum adiponectin
level association with breast cancer
risk: evidence from a case-control study. Asian Pac J Cancer Prev 2015;16:4945–8.
. Al Awadhi SA, Al Khaldi RM, Al Rammah T, et al. Associations of adipokines & insulin resistance with sex steroids in patients with breast cancer
. Indian J Med Res 2012;135:500–5.
. Al Khaldi RM, Al Mulla F, Al Awadhi S, et al. 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.
. Assiri AM, Kamel HF, Hassanien MF. Resistin, visfatin, adiponectin
, and leptin: risk of breast cancer
in pre- and postmenopausal Saudi females and their possible diagnostic and predictive implications as novel biomarkers. Dis Markers 2015;2015:253519.
. Cust AE, Stocks T, Lukanova A, et al. The influence of overweight and insulin resistance on breast cancer
risk and tumour stage at diagnosis: a prospective study. Breast Cancer
Res Treat 2009;113:567–76.
. Dalamaga M, Karmaniolas K, Papadavid E, et al. Elevated serum visfatin/nicotinamide phosphoribosyl-transferase levels are associated with risk of postmenopausal breast cancer
independently from adiponectin
, leptin, and anthropometric and metabolic parameters. Menopause 2011;18:1198–204.
. Georgiou GP, Provatopoulou X, Kalogera E, et al. Serum resistin is inversely related to breast cancer
risk in premenopausal women. Breast 2016;29:163–9.
. Gross AL, Newschaffer CJ, Hoffman-Bolton J, et al. Adipocytokines, inflammation, and breast cancer
risk in postmenopausal women: a prospective study. Cancer Epidemiol Biomarkers Prev 2013;22:1319–24.
. Gunter MJ, Wang T, Cushman M, et al. Circulating adipokines and inflammatory markers and postmenopausal breast cancer
risk. J Natl Cancer Inst 2015;107:djv169.
. Guo MM, Duan XN, Cui SD, et al. Circulating high-molecular-weight (HMW) adiponectin
level is related with breast cancer
risk better than total adiponectin
: a case-control study. PLoS One 2015;10:e0129246.
. Hancke K, Grubeck D, Hauser N, et al. Adipocyte fatty acid-binding protein as a novel prognostic factor in obese breast cancer
patients. Breast Cancer
Res Treat 2010;119:367–.
. Kang JH, Yu BY, Youn DS. Relationship of serum adiponectin
and resistin levels with breast cancer
risk. J Korean Med Sci 2007;22:117–21.
. Körner A, Pazaitou-Panayiotou K, Kelesidis T, et al. Total and high-molecular-weight adiponectin
in breast cancer
: in vitro and in vivo studies. J Clin Endocrinol Metab 2007;92:1041–8.
. Minatoya M, Kutomi G, Shima H, et al. Relation of serum adiponectin
levels and obesity with breast cancer
: a Japanese case-control study. Asian Pac J Cancer Prev 2014;15:8325–30.
. Ollberding NJ, Kim Y, Shvetsov YB, et al. Prediagnostic leptin, adiponectin
, C-reactive protein, and the risk of postmenopausal breast cancer
. Cancer Prev Res 2013;6:188–95.
. Ozmen HK, Erdemci B, Askin S, et al. Carnitine and adiponectin
levels in breast cancer
after radiotherapy. Open Med (Wars) 2017;12:189–94.
. Santillán-Benítez JG, Mendieta-Zerón H, Gómez-Oliván LM, et al. The tetrad BMI, leptin, leptin/adiponectin
(L/A) ratio and CA 15-3 are reliable biomarkers of breast cancer
. J Clin Lab Anal 2013;27:12–20.
. Shahar S, Salleh RM, Ghazali AR, et al. Roles of adiposity, lifetime physical activity and serum adiponectin
in occurrence of breast cancer
among Malaysian women in Klang Valley. Asian Pac J Cancer Prev 2010;11:61–6.
. Touvier M, Fezeu L, Ahluwalia N, et al. Association between prediagnostic biomarkers of inflammation and endothelial function and cancer risk: a nested case-control study. Am J Epidemiol 2013;177:3–13.
. Tworoger SS, Eliassen AH, Kelesidis T, et al. Plasma adiponectin
concentrations and risk of incident breast cancer
. J Clin Endocrinol Metab 2007;92:1510–6.
. Minatoya M, Kutomi G, Asakura S, et al. Relationship of serum isoflavone, insulin and adiponectin
levels with breast cancer
risk. Breast Cancer
. Crisóstomo J, Matafome P, Santos-Silva D, et al. Hyperresistinemia and metabolic dysregulation: a risky crosstalk in obese breast cancer
. Endocrine 2016;53:433–42.
. Azim HA Jr, Partridge AH. Biology of breast cancer
in young women. Breast Cancer
. Fletcher SJ, Sacca PA, Pistone-Creydt M, et al. Human breast adipose tissue: characterization of factors that change during tumor progression in human breast cancer
. J Exp Clin Cancer Res 2017;36:26.
. Nagaraju GP, Rajitha B, Aliya S, et al. The role of adiponectin
in obesity-associated female-specific carcinogenesis. Cytokine Growth Factor Rev 2016;31:37–48.
. Renehan AG, Tyson M, Egger M, et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis
of prospective observational studies. Lancet 2008;371:569–78.
. Loi S, Milne RL, Friedlander ML, et al. Obesity and outcomes in premenopausal and postmenopausal breast cancer
. Cancer Epidemiol Biomarkers Prev 2005;14:1686–91.
. Dalamaga M, Diakopoulos KN, Mantzoros CS. The role of adiponectin
in cancer: a review of current evidence. Endocr Rev 2012;33:547–94.
. Chandran M, Phillips SA, Ciaraldi T, et al. Adiponectin
: more than just another fat cell hormone? Diabetes Care 2003;26:2442–50.
. Barb D, Williams CJ, Neuwirth AK, et al. Adiponectin
in relation to malignancies: a review of existing basic research and clinical evidence. Am J Clin Nutr 2007;86:s858–66.
. Berg AH, Combs TP, Scherer PE. ACRP30/adiponectin
: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab 2002;13:84–9.
. Ziemke F, Mantzoros CS. Adiponectin
in insulin resistance: lessons from translational research. Am J Clin Nutr 2010;91:258S–61S.
. McTiernan A. Associations between energy balance and body mass index and risk of breast carcinoma in women from diverse racial and ethnic backgrounds in the U.S. Cancer 2000;88(Suppl):1248–55.
. Han DF, Zhou X, Hu MB, et al. Polymorphisms of estrogen-metabolizing genes and breast cancer
risk: a multigenic study. Chin Med J (Engl) 2005;118:1507–16.
. Tessitore L, Vizio B, Pesola D, et al. Adipocyte expression and circulating levels of leptin increase in both gynaecological and breast cancer
patients. Int J Oncol 2004;24:1529–35.
. Wolf I, Sadetzki S, Kanety H, et al. Adiponectin
, ghrelin, and leptin in cancer cachexia in breast and colon cancer patients. Cancer 2006;106:966–73.
. Jardé T, Caldefie-Chézet F, Goncalves-Mendes N, et al. Involvement of adiponectin
and leptin in breast cancer
: clinical and in vitro studies. Endocr Relat Cancer 2009;16:1197–210.
. Jardé T, Caldefie-Chézet F, Damez M, et al. Adiponectin
and leptin expression in primary ductal breast cancer
and in adjacent healthy epithelial and myoepithelial tissue. Histopathology 2008;53:484–7.
. Dieudonne MN, Bussiere M, Dos Santos E, et al. Adiponectin
mediates antiproliferative and apoptotic responses in human MCF7 breast cancer
cells. Biochem Biophys Res Commun 2006;345:271–9.
. Dos Santos E, Benaitreau D, Dieudonne MN, et al. Adiponectin
mediates an antiproliferative response in human MDA-MB 231 breast cancer
cells. Oncol Rep 2008;20:971–7.
. Falk Libby E, Liu J, Li YI, et al. Globular adiponectin
enhances invasion in human breast cancer
cells. Oncol Lett 2016;11:633–41.