Top

Published in:

01-09-2010 | Original paper

B-cell chronic lymphocytic leukemia risk in association with serum leptin and adiponectin: a case–control study in Greece

Authors: Maria Dalamaga, Bradley H. Crotty, Jessica Fargnoli, Evangelia Papadavid, Antigoni Lekka, Maria Triantafilli, Konstantinos Karmaniolas, Ilias Migdalis, Amalia Dionyssiou-Asteriou, Christos S. Mantzoros

Published in: Cancer Causes & Control | Issue 9/2010

Abstract

Aim

Leptin and adiponectin are two well-studied adipokines in relation to malignancies. In this study, we examined the association between leptin/adiponectin and risk of B-cell chronic lymphocytic leukemia (B-CLL), as well as the relationships between adipokines and several established prognostic factors of B-CLL.

Methods

Ninety-five patients with incident B-CLL and 95 hospital controls matched on age and gender were studied between 2001 and 2007, and blood samples were collected. Leptin, total and high molecular weight adiponectin, and prognostic markers of B-CLL were determined.

Results

Cases had a higher body mass index (BMI) than controls (p = 0.01) and lower levels of leptin (p < 0.01). Significantly more cases than controls presented a family history of lymphohematopoietic cancer (LHC) (p = 0.01). Higher serum leptin levels were associated with lower risk of B-CLL adjusting for age, gender, family history of LHC, BMI and serum adiponectin; the multivariate odds ratio comparing highest to lowest tertile was 0.05 (95% CI 0.01–0.29, p trend < 0.001); Adiponectin was not significantly different between cases and controls.

Conclusion

Leptin was found to be inversely associated with risk of CLL but in contrast to prior studies of CLL and hematologic malignancies, this study found no significant association between CLL and adiponectin.

Redaelli A, Laskin BL, Stephens JM, Botteman MF, Pashos CL (2004) The clinical and epidemiological burden of chronic lymphocytic leukaemia. Eur J Cancer Care 13:279–287CrossRef

Houlston RS, Sellick G, Yuille M, Matutes E, Catovsky D (2003) Causation of chronic lymphocytic leukemia–insights from familial disease. Leuk Res 27:871–876CrossRefPubMed

Andritsos L, Khoury H (2002) Chronic lymphocytic leukemia. Curr Treat Opin Oncol 3:225–231CrossRef

Cerhan JR, Janney CA, Vachon CM et al (2004) Anthropometric characteristics, physical activity, and risk of non-Hodgkin’s lymphoma subtypes and B-cell chronic lymphocytic leukemia: a prospective study. Am J Epidemiol 156:527–535CrossRef

Barb D, Williams CJ, Neuwirth AK, Mantzoros CS (2007) Adiponectin in relation to malignancies: a review of existing basic research and clinical evidence. Am J Clin Nutr 86:s858–s866PubMed

Larsson SC, Wolk A (2007) Obesity and risk of non-Hodgkin’s lymphoma: a meta-analysis. Int J Cancer 121:1564–1570CrossRefPubMed

Larsson SC, Wolk A (2008) Overweight and obesity and incidence of leukemia: a meta-analysis of cohort studies. Int J Cancer 122:1418–1421CrossRefPubMed

Barb D, Pazaitou-Panayiotou K, Mantzoros CS (2006) Adiponectin: a link between obesity and cancer. Expert Opin Investig Drugs 5:917–931CrossRef

Petridou E, Mantzoros CS, Dessypris N, Dikalioti SK, Trichopoulos D (2006) Adiponectin in relation to childhood myeloblastic leukaemia. Br J Cancer 94:156–160CrossRefPubMed

10.

Kelesidis I, Kelesidis T, Mantzoros CS (2006) Adiponectin and cancer: a systematic review. Br J Cancer 94:1221–1225CrossRefPubMed

11.

Bennett BD, Solar GP, Yuan JQ, Mathias J, Thomas GR, Matthews W (1996) A role for leptin and its cognate receptor in hematopoiesis. Curr Biol 6:1170–1180CrossRefPubMed

12.

Wex H, Ponelis E, Wex T, Dressendorfer R, Mittler U, Vorwerk P (2002) Plasma leptin and leptin receptor expression in childhood acute lymphoblastic leukemia. Int J Hematol 76:446–452CrossRefPubMed

13.

Hino M, Nakao T, Yamane T, Ohta K, Takubo T, Tatsumi N (2000) Leptin receptor and leukemia. Leuk Lymphoma 36:457–461CrossRefPubMed

14.

Pamuk GE, Demir M, Harmandar F, Yesil Y, Turgut B, Vural O (2006) Leptin and resistin levels in serum of patients with hematologic malignancies: correlation with clinical characteristics. Exp Oncol 8:241–244

15.

Nakao T, Hino M, Yamane T, Nishizawa Y, Morii H, Tatsumi N (1998) Expression of the leptin receptor in human leukaemic blast cells. Br J Haematol 102:740–745CrossRefPubMed

16.

Yamauchi T, Kamon J, Waki H et al (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 7:941–946CrossRefPubMed

17.

Wang Y, Lam KS, Xu A (2007) Adiponectin as a negative regulator in obesity-related mammary carcinogenesis. Cell Res 17:280–282CrossRefPubMed

18.

Brakenhielm E, Veitonmaki N, Cao R et al (2004) Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci 101:2476–2481CrossRefPubMed

19.

Kadowaki T, Yamauchi T (2005) Adiponectin and adiponectin receptors. Endocr Rev 26:439–451CrossRefPubMed

20.

Waki H, Yamauchi T, Kamon J et al (2005) Generation of globular fragment of adiponectin by leukocyte elastase secreted by monocytic cell line THP-1. Endocrinology 146:790–796CrossRefPubMed

21.

Waki H, Yamauchi T, Kamon J et al (2003) Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. J Biol Chem 278:40352–40363CrossRefPubMed

22.

Tsuchida A, Yamauchi T, Ito Y et al (2004) Insulin/Foxo1 pathway regulates expression levels of adiponectin receptors and adiponectin sensitivity. J Biol Chem 279:30817–30822CrossRefPubMed

23.

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

24.

Korner A, Pazaitou-Panayiotou K, Kelesidis T et al (2007) Total and high-molecular-weight adiponectin in breast cancer: in vitro and in vivo studies. J Clin Endocrinol Metab 92:1041–1048CrossRefPubMed

25.

Dalamaga M, Karmaniolas K, Nikolaidou A et al (2008) Adiponectin and resistin are associated with risk for myelodysplastic syndrome, independently from the insulin-like growth factor-I (IGF-I) system. Eur J Cancer 44:1744–1753CrossRefPubMed

26.

Dalamaga M, Nikolaidou A, Karmaniolas K et al (2007) Circulating adiponectin and leptin in relation to myelodysplastic syndrome: a case-control study. Oncology 73:26–32CrossRefPubMed

27.

Dalamaga M, Karmaniolas K, Panagiotou A et al (2009) Low circulating adiponectin and resistin, but not leptin, levels are associated with multiple myeloma risk: a case-control study. Cancer Causes Control 20:193–199CrossRefPubMed

28.

Avcu F, Ural AU, Yilmaz MI, Bingol N, Nevruz O, Caglar K (2006) Association of plasma adiponectin concentrations with chronic lymphocytic leukemia and myeloproliferative diseases. Int J Hematol 83:254–258CrossRefPubMed

29.

Pamuk GE, Turgut B, Demir M, Vural O (2006) Increased adiponectin level in non-Hodgkin lymphoma and its relationship with interleukin-10. Correlation with clinical features and outcome. J Exp Clin Cancer Res 25:537–541PubMed

30.

Cheson BD, Bennett JM, Grever M et al (1996) National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 87:4990–4997PubMed

31.

Harris NL, Jaffe ES, Diebold J et al (1999) The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November, 1997. Ann Oncol 10:1419–1432CrossRefPubMed

32.

Binet JL, Auquier A, Dighiero G et al (1981) A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer 48:198–206CrossRefPubMed

33.

Oscier DG, Matutes E, Copplestone A et al (1997) Atypical lymphocyte morphology: an adverse prognostic factor for disease progression in stage A CLL independent of trisomy 12. Br J Hematol 98:934–939CrossRef

34.

Wolk A, Gridley G, Svensson M et al (2001) A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control 12:13–21CrossRefPubMed

35.

Yokota T, Oritani K, Takahashi I et al (2000) Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 96:1723–1732PubMed

36.

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

37.

Arditi JD, Venihaki M, Karalis KP, Chrousos GP (2007) Antiproliferative effect of adiponectin on MCF7 breast cancer cells: a potential hormonal link between obesity and cancer. Hormone and metabolic research Hormon- und Stoffwechselforschung 39:9–13CrossRef

38.

Wang Y, Lam JB, Lam KS et al (2006) Adiponectin modulates the glycogen synthase kinase-3beta/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice. Cancer Res 66:11462–11470CrossRefPubMed

39.

DiMascio L, Voermans C, Uqoezwa M et al (2007) Identification of adiponectin as a novel hemopoietic stem cell growth factor. J Immunol 178:3511–35120PubMed

40.

Iversen PO, Wiig H (2005) Tumor necrosis factor alpha and adiponectin in bone marrow interstitial fluid from patients with acute myeloid leukemia inhibit normal hematopoiesis. Clin Cancer Res 11:6793–6799CrossRefPubMed

41.

Yokota T, Meka CS, Kouro T et al (2003) Adiponectin, a fat cell product, influences the earliest lymphocyte precursors in bone marrow cultures by activation of the cyclooxygenase-prostaglandin pathway in stromal cells. J Immunol 171:5091–5099PubMed

42.

Konturek PC, Burnat G, Rau T, Hahn EG, Konturek S (2008) Effect of adiponectin and ghrelin on apoptosis of Barrett adenocarcinoma cell line. Dig Dis Sci 53:597–605CrossRefPubMed

43.

Molica S, Vitelli G, Cutrona G et al (2008) Prognostic relevance of serum levels and cellular expression of adiponectin in B-cell chronic lymphocytic leukemia. Int J Hematol 88:374–380CrossRefPubMed

44.

Bruserud Ø, Huang TS, Glenjen N, Gjertsen BT, Foss B (2002) Leptin in human acute myelogenous leukemia: studies of in vivo levels and in vitro effects on native functional leukemia blasts. Haematologica 87:584–595PubMed

45.

Hamed NA, Sharaki OA, Zeidan MM (2003) Leptin in acute leukaemias: relationship to interleukin-6 and vascular endothelial growth factor. Egypt J Immunol 10:57–66PubMed

46.

Considine R, Sinha M, Heiman M (1996) Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334:292–295CrossRefPubMed

47.

Zhang Y, Scarpace P (2006) The role of leptin in leptin resistance and obesity. Physiol Behav 88:249–256CrossRefPubMed

48.

Boden G, Chen X, Mozzoli M, Ryan I (1996) Effect of fasting on serum leptin in normal human subjects. J Clin Endocrinol Metab 81:3419–3423CrossRefPubMed

49.

Chan J, Heist K, DePaoli A, Veldhuis J (2003) The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men. J Clin Invest 11:1409–1421

50.

Gainsford T, Willson TA, Metcalf D et al (1996) Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells. Proc Natl Acad Sci USA 93:14564–14568CrossRefPubMed

51.

Fantuzzi G, Faggioni R (2000) Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol 68:437–446PubMed

52.

Konopleva M, Mikhail A, Estrov Z et al (1999) Expression and function of leptin receptor isoforms in myeloid leukemia and myelodysplastic syndromes: proliferative and anti-apoptotic activities. Blood 93:1668–1676PubMed

53.

Berner HS, Lyngstadaas SP, Spahr A et al (2004) Adiponectin and its receptors are expressed in bone-forming cells. Bone 35:842–849CrossRefPubMed

Title: B-cell chronic lymphocytic leukemia risk in association with serum leptin and adiponectin: a case–control study in Greece
Authors: Maria Dalamaga
Bradley H. Crotty
Jessica Fargnoli
Evangelia Papadavid
Antigoni Lekka
Maria Triantafilli
Konstantinos Karmaniolas
Ilias Migdalis
Amalia Dionyssiou-Asteriou
Christos S. Mantzoros
Publication date: 01-09-2010
Publisher: Springer Netherlands
Published in: Cancer Causes & Control / Issue 9/2010
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI: https://doi.org/10.1007/s10552-010-9573-y

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Aim

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 9/2010

Non-steroidal anti-inflammatory drug (NSAID) use and breast cancer risk in the Western New York Exposures and Breast Cancer (WEB) Study

Tobacco and alcohol use increases the risk of both HPV-associated and HPV-independent head and neck cancers

Tea consumption and risk of ovarian cancer

Pickled meat consumption and colorectal cancer (CRC): a case–control study in Newfoundland and Labrador, Canada

Meat, poultry and fish and risk of colorectal cancer: pooled analysis of data from the UK dietary cohort consortium

Impact of PSA testing and prostatic biopsy on cancer incidence and mortality: comparative study between the Republic of Ireland and Northern Ireland

Keynote webinar | Spotlight on antibody–drug conjugates in cancer