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Systematic review/Meta-analysis

Association between circulating leptin concentration and G-2548A gene polymorphism in patients with breast cancer: a meta-analysis

Ji-Qing Hao, Qian-Kun Zhang, Yi-Xin Zhou, Li-Hao Chen, Peng-Fei Wu

Arch Med Sci
Online publish date: 2018/05/15
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The aim of this meta-analysis was to summarize the evidence on the serum/plasma leptin concentrations in breast cancer (BC) patients, as well as the associations between leptin G-2548A gene polymorphisms and susceptibility to BC.

Material and methods
Potentially relevant studies about serum/plasma leptin levels and leptin G-2548A gene polymorphism were selected using the electronic databases PubMed, EMBASE and The Cochrane Library (from January 1 1995 to Jun 30 2017, no language restrictions). The potential sources of heterogeneity were assessed by the Q statistic and quantified using I2; publication bias was qualitatively assessed by funnel plot and quantitatively assessed by Egger’s linear regression test.

A total of 1141 articles were retrieved after database searches, and 27 studies with 9516 subjects (4542 BC patients/4974 controls) were finally included. The results indicated that BC patients had significantly higher leptin levels compared with healthy controls (SMD = 1.65, 95% CI: 1.21–2.09, p < 0.001), but there was no association between leptin G-2548A polymorphism and BC (OR = 1.05, 95% CI: 0.80–1.39, p = 0.722). Subgroup analyses demonstrated increased leptin levels in BC patients of different region, race, body mass index and waist circumference.

Our results revealed a significantly higher leptin level in BC patients than in healthy controls, but no association between leptin G-2548A polymorphism and BC susceptibility was found.


breast cancer, leptin, gene polymorphism, meta-analysis

Pignatelli M, Cocca C, Santos A, Perez-Castillo A. Enhancement of BRCA1 gene expression by the peroxisome proliferator-activated receptor gamma in the MCF-7 breast cancer cell line. Oncogene 2003; 22: 5446-50.
Housa D, Housova J, Vernerova Z, Haluzik M. Adipocytokines and cancer. Physiol Res 2006; 55: 233-44.
Carrasco E, Garrido JM, Alvarez PJ, et al. Meroxest improves the prognosis of immunocompetent C57BL/6 mice with allografts of E0771 mouse breast tumor cells. Arch Med Sci 2016; 12: 919-27.
Nowikiewicz T, Wnuk P, Malkowski B, Kurylcio A, Kowalewski J, Zegarski W. Application of artificial neural networks for predicting presence of non-sentinel lymph node metastases in breast cancer patients with positive sentinel lymph node biopsies. Arch Med Sci 2017; 13: 1399-407.
Wang XJ, Yuan SL, Lu Q, et al. Potential involvement of leptin in carcinogenesis of hepatocellular carcinoma. World J Gastroenterol 2004; 10: 2478-81.
Russo VC, Metaxas S, Kobayashi K, Harris M, Werther GA. Antiapoptotic effects of leptin in human neuroblastoma cells. Endocrinology 2004; 145: 4103-12.
O’Brien SN, Welter BH, Price TM. Presence of leptin in breast cell lines and breast tumors. Biochem Biophys Res Commun 1999; 259: 695-8.
Ishikawa M, Kitayama J, Nagawa H. Enhanced expression of leptin and leptin receptor (OB-R) in human breast cancer. Clin Cancer Res 2004; 10: 4325-31.
Hu X, Juneja SC, Maihle NJ, Cleary MP. Leptin: a growth factor in normal and malignant breast cells and for normal mammary gland development. J Natl Cancer Inst 2002; 94: 1704-11.
Yin N, Wang D, Zhang H, et al. Molecular mechanisms involved in the growth stimulation of breast cancer cells by leptin. Cancer Res 2004; 64: 5870-5.
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.
Chen DC, Chung YF, Yeh YT, et al. Serum adiponectin and leptin levels in Taiwanese breast cancer patients. Cancer Lett 2006; 237: 109-14.
Mantzoros CS, Bolhke K, Moschos S, Cramer DW. Leptin in relation to carcinoma in situ of the breast: a study of pre-menopausal cases and controls. Int J Cancer 1999; 80: 523-6.
Stattin P, Soderberg S, Biessy C, et al. Plasma leptin and breast cancer risk: a prospective study in northern Sweden. Breast Cancer Res Treat 2004; 86: 191-6.
Snoussi K, Strosberg AD, Bouaouina N, Ben Ahmed S, Helal AN, Chouchane L. Leptin and leptin receptor polymorphisms are associated with increased risk and poor prognosis of breast carcinoma. BMC Cancer 2006; 6: 38.
Rostami S, Kohan L, Mohammadianpanah M. The LEP G-2548A gene polymorphism is associated with age at menarche and breast cancer susceptibility. Gene 2015; 557: 154-7.
Rodrigo C, Tennekoon KH, Karunanayake EH, De Silva K, Amarasinghe I, Wijayasiri A. Circulating leptin, soluble leptin receptor, free leptin index, visfatin and selected leptin and leptin receptor gene polymorphisms in sporadic breast cancer. Endocr J 2017; 64: 393-401.
Mahmoudi R, Noori Alavicheh B, Nazer Mozaffari MA, Fararouei M, Nikseresht M. Polymorphisms of leptin (-2548 G/A) and leptin receptor (Q223R) genes in Iranian women with breast cancer. Int J Genomics 2015; 2015: 132720.
Karakus N, Kara N, Ulusoy AN, Ozaslan C, Tural S, Okan I. Evaluation of CYP17A1 and LEP gene polymorphisms in breast cancer. Oncol Res Treat 2015; 38: 418-22.
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557-60.
Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539-58.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-34.
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.
Dalamaga M, Karmaniolas K, Papadavid E, Pelekanos N, Sotiropoulos G, Lekka A. Hyperresistinemia is associated with postmenopausal breast cancer. Menopause 2013; 20: 845-51.
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.
Ollberding NJ, Kim Y, Shvetsov YB, et al. Prediagnostic leptin, adiponectin, C-reactive protein, and the risk of postmenopausal breast cancer. Cancer Prev Res (Phila) 2013; 6: 188-95.
Romero-Figueroa Mdel S, Garduno-Garcia Jde J, Duarte-Mote J, Matute-Gonzalez G, Gomez-Villanueva A, De la Cruz-Vargas J. Insulin and leptin levels in obese patients with and without breast cancer. Clin Breast Cancer 2013; 13: 482-5.
Al Awadhi SA, Al Khaldi RM, Al Rammah T, Kapila K, Mojiminiyi OA. Associations of adipokines and insulin resistance with sex steroids in patients with breast cancer. Indian J Med Res 2012; 135: 500-5.
Aliustaoglu M, Bilici A, Gumus M, et al. Preoperative serum leptin levels in patients with breast cancer. Med Oncol 2010; 27: 388-91.
Maccio A, Madeddu C, Gramignano G, et al. Correlation of body mass index and leptin with tumor size and stage of disease in hormone-dependent postmenopausal breast cancer: preliminary results and therapeutic implications. J Mol Med (Berl) 2010; 88: 677-86.
Wu MH, Chou YC, Chou WY, et al. Circulating levels of leptin, adiposity and breast cancer risk. Br J Cancer 2009; 100: 578-82.
Hancke K, Grubeck D, Hauser N, Kreienberg R, Weiss JM. Adipocyte fatty acid-binding protein as a novel prognostic factor in obese breast cancer patients. Breast Cancer Res Treat 2009; 119: 367-77.
Han CZ, Du LL, Jing JX, et al. Associations among lipids, leptin, and leptin receptor gene Gin223Arg polymorphisms and breast cancer in China. Biol Trace Elem Res 2008; 126: 38-48.
Liu CL, Chang YC, Cheng SP, et al. The roles of serum leptin concentration and polymorphism in leptin receptor gene at codon 109 in breast cancer. Oncology 2007; 72: 75-81.
Hou WK, Xu YX, Yu T, et al. Adipocytokines and breast cancer risk. Chin Med J (Engl) 2007; 120: 1592-6.
Han C, Zhang HT, Du L, et al. Serum levels of leptin, insulin, and lipids in relation to breast cancer in China. Endocrine 2005; 26: 19-24.
Ozet A, Arpaci F, Yilmaz MI, et al. Effects of tamoxifen on the serum leptin level in patients with breast cancer. Jpn J Clin Oncol 2001; 31: 424-7.
Tessitore L, Vizio B, Jenkins O, et al. Leptin expression in colorectal and breast cancer patients. Int J Mol Med 2000; 5: 421-6.
Petridou E, Papadiamantis Y, Markopoulos C, Spanos E, Dessypris N, Trichopoulos D. Leptin and insulin growth factor I in relation to breast cancer (Greece). Cancer Causes Control 2000; 11: 383-8.
Mohammadzadeh G, Ghaffari MA, Bafandeh A, Hosseini SM, Ahmadi B. The relationship between -2548 G/A leptin gene polymorphism and risk of breast cancer and serum leptin levels in Ahvazian women. Iran J Cancer Prev 2015; 8: 100-8.
Cleveland RJ, Gammon MD, Long CM, et al. Common genetic variations in the LEP and LEPR genes, obesity and breast cancer incidence and survival. Breast Cancer Res Treat 2010; 120: 745-52.
Biesiada LA, Glowacka E, Krekora M, Sobantka S, Krokocka A, Krasomski G. The impact of excessive maternal weight on the nutritional status of the fetus – the role of leptin. Arch Med Sci 2016; 12: 394-401.
Begenik H, Aslan M, Dulger AC, et al. Serum leptin levels in gastric cancer patients and the relationship with insulin resistance. Arch Med Sci 2015; 11: 346-52.
Motawi T, Salman T, Shaker O, Abdelhamid A. Association of polymorphism in adiponectin (+45 T/G) and leptin (-2548 G/A) genes with type 2 diabetes mellitus in male Egyptians. Arch Med Sci 2015; 11: 937-44.
van den Brandt PA, Spiegelman D, Yaun SS, et al. Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol 2000; 152: 514-27.
Calle EE, Thun MJ. Obesity and cancer. Oncogene 2004; 23: 6365-78.
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