J Gynecol Oncol.  2013 Oct;24(4):336-341. 10.3802/jgo.2013.24.4.336.

Serum leptin, adiponectin and endometrial cancer risk in Chinese women

• Ma Y
• Liu Z
• Zhang Y
• Lu B

• KMID: 2177875
• DOI: http://doi.org/10.3802/jgo.2013.24.4.336

Abstract

OBJECTIVE
To investigate the relationship between serum concentrations of leptin or adiponectin, and endometrial carcinoma in Chinese women.
METHODS
We conducted a case-control study of a total of 516 Chinese women to detect the relationships between serum concentrations of leptin or adiponectin, and endometrial carcinoma in Chinese women. The study subject constituted 206 cases of endometrial cancer and 310 normal controls.
RESULTS
Patients with endometrial carcinoma had higher serum leptin concentrations than controls (28.8+/-2.2 ug/L vs. 19.8+/-1.4 ug/L; p<0.001). The adiponectin levels in patients were lower than in controls with borderline statistical significance (2,330.7+/-180.5 ug/L vs. 2,583.9+/-147.2 ug/L; p=0.078). Logistic regression analysis confirmed the associations between leptin or adiponectin, and endometrial carcinoma after adjustment for age, body mass index, fasting insulin, serum glucose, cholesterol, triglycerides, and high-density lipoprotein cholesterol (odds ratio for the top tertile vs. the bottom tertile: leptin 2.05; 95% confidence interval [CI], 1.28 to 3.29; p<0.001; adiponectin 0.52; 95% CI, 0.32 to 0.83; p<0.001).
CONCLUSION
Increased leptin or decreased adiponectin levels are associated with endometrial carcinoma.

Keyword

Adiponectin; Endometrial carcinoma; Insulin resistance; Leptin

MeSH Terms

Adiponectin
Asian Continental Ancestry Group
Body Mass Index
Case-Control Studies
Cholesterol
Endometrial Neoplasms
Fasting
Female
Glucose
Humans
Insulin
Insulin Resistance
Leptin
Lipoproteins
Logistic Models
Triglycerides
Adiponectin
Cholesterol
Glucose
Insulin
Leptin
Lipoproteins
Triglycerides

Reference

1. Cust AE, Kaaks R, Friedenreich C, Bonnet F, Laville M, Tjonneland A, et al. Metabolic syndrome, plasma lipid, lipoprotein and glucose levels, and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Endocr Relat Cancer. 2007; 14:755–767.

2. Zhang Y, Liu Z, Yu X, Zhang X, Lu S, Chen X, et al. The association between metabolic abnormality and endometrial cancer: a large case-control study in China. Gynecol Oncol. 2010; 117:41–46.

3. Kaaks R, Lukanova A, Kurzer MS. Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiol Biomarkers Prev. 2002; 11:1531–1543.

4. Cust AE, Allen NE, Rinaldi S, Dossus L, Friedenreich C, Olsen A, et al. Serum levels of C-peptide, IGFBP-1 and IGFBP-2 and endometrial cancer risk; results from the European prospective investigation into cancer and nutrition. Int J Cancer. 2007; 120:2656–2664.

5. Zhan Y, Wang J, Ma Y, Liu Z, Xu H, Lu S, et al. Serum insulin-like, growth factor binding protein-related protein 1 (IGFBP-rP1) and endometrial cancer risk in Chinese women. Int J Cancer. 2013; 132:411–416.

6. Paz-Filho G, Lim EL, Wong ML, Licinio J. Associations between adipokines and obesity-related cancer. Front Biosci (Landmark Ed). 2011; 16:1634–1650.

7. van Kruijsdijk RC, van der Wall E, Visseren FL. Obesity and cancer: the role of dysfunctional adipose tissue. Cancer Epidemiol Biomarkers Prev. 2009; 18:2569–2578.

8. Forney JP, Milewich L, Chen GT, Garlock JL, Schwarz BE, Edman CD, et al. Aromatization of androstenedione to estrone by human adipose tissue in vitro: correlation with adipose tissue mass, age, and endometrial neoplasia. J Clin Endocrinol Metab. 1981; 53:192–199.

9. Gnacinska M, Malgorzewicz S, Stojek M, Lysiak-Szydłowska W, Sworczak K. Role of adipokines in complications related to obesity: a review. Adv Med Sci. 2009; 54:150–157.

10. Hanley AJ, Bowden D, Wagenknecht LE, Balasubramanyam A, Langfeld C, Saad MF, et al. Associations of adiponectin with body fat distribution and insulin sensitivity in nondiabetic Hispanics and African-Americans. J Clin Endocrinol Metab. 2007; 92:2665–2671.

11. Finucane FM, Luan J, Wareham NJ, Sharp SJ, O'Rahilly S, Balkau B, et al. Correlation of the leptin:adiponectin ratio with measures of insulin resistance in non-diabetic individuals. Diabetologia. 2009; 52:2345–2349.

12. Cymbaluk A, Chudecka-Głaz A, Rzepka-Gorska I. Leptin levels in serum depending on body mass index in patients with endometrial hyperplasia and cancer. Eur J Obstet Gynecol Reprod Biol. 2008; 136:74–77.

13. Yuan SS, Tsai KB, Chung YF, Chan TF, Yeh YT, Tsai LY, et al. Aberrant expression and possible involvement of the leptin receptor in endometrial cancer. Gynecol Oncol. 2004; 92:769–775.

14. Petridou E, Belechri M, Dessypris N, Koukoulomatis P, Diakomanolis E, Spanos E, et al. Leptin and body mass index in relation to endometrial cancer risk. Ann Nutr Metab. 2002; 46:147–151.

15. 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; 88:993–997.

16. 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; 89:1160–1163.

17. Rzepka-Gorska I, Bedner R, Cymbaluk-Ploska A, Chudecka-Glaz A. Serum adiponectin in relation to endometrial cancer and endometrial hyperplasia with atypia in obese women. Eur J Gynaecol Oncol. 2008; 29:594–597.

18. Cust AE, Kaaks R, Friedenreich C, Bonnet F, Laville M, Lukanova A, et al. Plasma adiponectin levels and endometrial cancer risk in pre- and postmenopausal women. J Clin Endocrinol Metab. 2007; 92:255–263.

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

20. Soliman PT, Cui X, Zhang Q, Hankinson SE, Lu KH. Circulating adiponectin levels and risk of endometrial cancer: the prospective Nurses' Health Study. Am J Obstet Gynecol. 2011; 204:167.e1–167.e5.

21. Ashizawa N, Yahata T, Quan J, Adachi S, Yoshihara K, Tanaka K. Serum leptin-adiponectin ratio and endometrial cancer risk in postmenopausal female subjects. Gynecol Oncol. 2010; 119:65–69.

22. Huang YL, Huang W, Long SK, Li L, Tang BJ, Yang B. Analysis of 1466 endometrial carcinomas in inpatients in Guangxi Zhuang Autonomous region: a 20 years' analysis. Acad J Sec Mil Med Univ. 2007; 28:681–684.

23. Dallal CM, Brinton LA, Bauer DC, Buist DS, Cauley JA, Hue TF, et al. Obesity-related hormones and endometrial cancer among postmenopausal women: a nested case-control study within the B~FIT cohort. Endocr Relat Cancer. 2013; 20:151–160.

24. Luhn P, Dallal CM, Weiss JM, Black A, Huang WY, Lacey JV Jr, et al. Circulating adipokine levels and endometrial cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev. 2013; 22:1304–1312.

25. Friedenreich CM, Langley AR, Speidel TP, Lau DC, Courneya KS, Csizmadi I, et al. Case-control study of markers of insulin resistance and endometrial cancer risk. Endocr Relat Cancer. 2012; 19:785–792.

26. Garaulet M, Perex-Llamas F, Fuente T, Zamora S, Tebar FJ. Anthropometric, computed tomography and fat cell data in an obese population: relationship with insulin, leptin, tumor necrosis factor-alpha, sex hormone-binding globulin and sex hormones. Eur J Endocrinol. 2000; 143:657–666.

27. Wu X, Yan Q, Zhang Z, Du G, Wan X. Acrp30 inhibits leptin-induced metastasis by downregulating the JAK/STAT3 pathway via AMPK activation in aggressive SPEC-2 endometrial cancer cells. Oncol Rep. 2012; 27:1488–1496.

28. Catalano S, Giordano C, Rizza P, Gu G, Barone I, Bonofiglio D, et al. Evidence that leptin through STAT and CREB signaling enhances cyclin D1 expression and promotes human endometrial cancer proliferation. J Cell Physiol. 2009; 218:490–500.

29. Sharma D, Saxena NK, Vertino PM, Anania FA. Leptin promotes the proliferative response and invasiveness in human endometrial cancer cells by activating multiple signal-transduction pathways. Endocr Relat Cancer. 2006; 13:629–640.

30. Cong L, Gasser J, Zhao J, Yang B, Li F, Zhao AZ. Human adiponectin inhibits cell growth and induces apoptosis in human endometrial carcinoma cells, HEC-1-A and RL95 2. Endocr Relat Cancer. 2007; 14:713–720.

31. Landskroner-Eiger S, Qian B, Muise ES, Nawrocki AR, Berger JP, Fine EJ, et al. Proangiogenic contribution of adiponectin toward mammary tumor growth in vivo. Clin Cancer Res. 2009; 15:3265–3276.

32. Kim KY, Baek A, Hwang JE, Choi YA, Jeong J, Lee MS, et al. Adiponectin-activated AMPK stimulates dephosphorylation of AKT through protein phosphatase 2A activation. Cancer Res. 2009; 69:4018–4026.