Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2008

Open Access 01-12-2008 | Research article

Leptin receptor Gln223Arg polymorphism and breast cancer risk in Nigerian women: A case control study

Authors: Michael N Okobia, Clareann H Bunker, Seymour J Garte, Joseph M Zmuda, Emmanuel R Ezeome, Stanley N Anyanwu, Emmanuel E Uche, Lewis H Kuller, Robert E Ferrell, Emanuela Taioli

Published in: BMC Cancer | Issue 1/2008

Login to get access

Abstract

Background

Leptin, a 16 kDa polypeptide hormone, implicated in various physiological processes, exerts its action through the leptin receptor, a member of the class I cytokine receptor family. Both leptin and leptin receptor have recently been implicated in processes leading to breast cancer initiation and progression in animal models and humans. An A to G transition mutation in codon 223 in exon 6 of the leptin receptor gene, resulting in glutamine to arginine substitution (Gln223Arg), lies within the first of two putative leptin-binding regions and may be associated with impaired signaling capacity of the leptin receptor. This study was designed to assess the role of this polymorphism in breast cancer susceptibility in Nigerian women.

Methods

We utilized a polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay to evaluate the association between the Gln223Arg polymorphism of the leptin receptor gene and breast risk in Nigeria in a case control study involving 209 women with breast cancer and 209 controls without the disease. Study participants were recruited from surgical outpatient clinics and surgical wards of four University Teaching Hospitals located in Midwestern and southeastern Nigeria between September 2002 and April 2004.

Results

Premenopausal women carrying at least one LEPR 223Arg allele were at a modestly increased risk of breast cancer after adjusting for confounders (OR = 1.8, 95% confidence interval [CI] 1.0–3.2, p = 0.07). There was no association with postmenopausal breast cancer risk (OR = 0.9, 95% CI 0.4–1.8, p = 0.68).

Conclusion

Our results suggest that the LEPR Gln223Arg polymorphism in the extracellular domain of the LEPR receptor gene is associated with a modestly increased risk of premenopausal breast cancer in Nigerian women.
Literature
1.
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM: Positional cloning of the mouse obese gene and its human homologue. Nature. 1994, 372: 425-432. 10.1038/372425a0.CrossRefPubMed
2.
Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P: Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science. 1995, 269: 546-549. 10.1126/science.7624778.CrossRefPubMed
3.
Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, et al: Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 1995, 269: 543-546. 10.1126/science.7624777.CrossRefPubMed
4.
Bennett BD, Solar GP, Yuan JQ, Mathias J, Thomas GR, Matthews W: A role for leptin and its cognate receptor in hematopoiesis. Curr Biol. 1996, 6: 1170-1180. 10.1016/S0960-9822(02)70684-2.CrossRefPubMed
5.
Bouloumie A, Drexler HC, Lafontan M, Busse R: Leptin, the product of Ob gene, promotes angiogenesis. Circ Res. 1998, 83: 1059-1066.CrossRefPubMed
6.
Loffreda S, Yang SQ, Lin HZ, Karp CL, Brengman ML, Wang DJ, et al: Leptin regulates proinflammatory immune responses. FASEB J. 1998, 12: 57-65.PubMed
7.
Lee GH, Proenca R, Montez JM, Carroll KM, Darvishzadeh JG, Lee JI, et al: Abnormal splicing of the leptin receptor in diabetic mice. Nature. 1996, 379: 632-635. 10.1038/379632a0.CrossRefPubMed
8.
9.
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: 1704-1711.CrossRefPubMed
10.
Dieudonne MN, Machinal-Quelin F, Serazin-Leroy V, Leneveu MC, Pecquery R, Giudicelli Y: Leptin mediates a proliferative response in human MCF7 breast cancer cells. Biochem Biophys Res Commun. 2002, 293: 622-628. 10.1016/S0006-291X(02)00205-X.CrossRefPubMed
11.
Laud K, Gourdou I, Pessemesse L, Peyrat JP, Djiane J: Identification of leptin receptors in human breast cancer: functional activity in the T47-D breast cancer cell line. Mol Cell Endocrinol. 2002, 188: 219-226. 10.1016/S0303-7207(01)00678-5.CrossRefPubMed
12.
Okumura M, Yamamoto M, Sakuma H, Kojima T, Maruyama T, Jamali M, et al: Leptin and high glucose stimulate cell proliferation in MCF-7 human breast cancer cells: reciprocal involvement of PKC-alpha and PPAR expression. Biochim Biophys Acta. 2002, 1592: 107-116.CrossRefPubMed
13.
Chung WK, Power-Kehoe L, Chua M, Chu F, Aronne L, Huma Z, et al: Exonic and intronic sequence variation in the human leptin receptor gene (LEPR). Diabetes. 1997, 46: 1509-1511.CrossRefPubMed
14.
Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, et al: Identification and expression cloning of a leptin receptor, OB-R. Cell. 1995, 83: 1263-1271. 10.1016/0092-8674(95)90151-5.CrossRefPubMed
15.
Phillips MS, Liu Q, Hammond HA, Dugan V, Hey PJ, Caskey CJ, et al: Leptin receptor missense mutation in the fatty Zucker rat. Nat Genet. 1996, 13: 18-19. 10.1038/ng0596-18.CrossRefPubMed
16.
Quinton ND, Lee AJ, Ross RJ, Eastell R, Blakemore AI: A single nucleotide polymorphism (SNP) in the leptin receptor is associated with BMI, fat mass and leptin levels in postmenopausal Caucasian women. Hum Genet. 2001, 108: 233-236. 10.1007/s004390100468.CrossRefPubMed
17.
Tessitore L, Vizio B, Pesola D, Cecchini F, Mussa A, Argiles JM, et al: Adipocyte expression and circulating levels of leptin increase in both gynaecological and breast cancer patients. Int J Oncol. 2004, 24: 1529-1535.PubMed
18.
Han C, Zhang HT, Du L, Liu X, Jing J, Zhao X, et al: Serum levels of leptin, insulin, and lipids in relation to breast cancer in china. Endocrine. 2005, 26: 19-24. 10.1385/ENDO:26:1:019.CrossRefPubMed
19.
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: 383-388. 10.1023/A:1008903727238.CrossRefPubMed
20.
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: 523-526. 10.1002/(SICI)1097-0215(19990209)80:4<523::AID-IJC7>3.0.CO;2-C.CrossRefPubMed
21.
Yiannakouris N, Yannakoulia M, Melistas L, Chan JL, Klimis-Zacas D, Mantzoros CS: The Q223R polymorphism of the leptin receptor gene is significantly associated with obesity and predicts a small percentage of body weight and body composition variability. J Clin Endocrinol Metab. 2001, 86: 4434-4439. 10.1210/jc.86.9.4434.CrossRefPubMed
22.
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: 38-10.1186/1471-2407-6-38.CrossRefPubMedPubMedCentral
23.
Woo HY, Park H, Ki CS, Park YL, Bae WG: Relationships among serum leptin, leptin receptor gene polymorphisms, and breast cancer in Korea. Cancer Lett. 2006, 237: 137-142. 10.1016/j.canlet.2005.05.041.CrossRefPubMed
24.
Okobia M, Bunker C, Zmuda J, Kammerer C, Vogel V, Uche E, et al: Cytochrome P4501A1 genetic polymorphisms and breast cancer risk in Nigerian women. Breast Cancer Res Treat. 2005, 94: 285-293. 10.1007/s10549-005-9022-x.CrossRefPubMed
25.
Okobia MN, Bunker CH, Zmuda JM, Ezeome ER, Anyanwu SN, Uche EE, et al: Simple tandem repeat (TTTA)n polymorphism in CYP19 (aromatase) gene and breast cancer risk in Nigerian women. J Carcinog. 2006, 5: 12-10.1186/1477-3163-5-12.CrossRefPubMedPubMedCentral
26.
Okobia M, Bunker C, Zmuda J, Kammerer C, Vogel V, Uche E, et al: Case-control study of risk factors for breast cancer in Nigerian women. Int J Cancer. 2006, 119: 2179-2185. 10.1002/ijc.22102.CrossRefPubMed
27.
Okobia MN, Bunker CH, Zmuda JM, Osime U, Ezeome ER, Anyanwu SN, et al: Anthropometry and breast cancer risk in nigerian women. Breast J. 2006, 12: 462-466. 10.1111/j.1075-122X.2006.00304.x.CrossRefPubMed
28.
Paracchini V, Pedotti P, Taioli E: Genetics of leptin and obesity: a HuGE review. Am J Epidemiol. 2005, 162: 101-114. 10.1093/aje/kwi174.CrossRefPubMed
29.
30.
Chehab FF, Lim ME, Lu R: Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet. 1996, 12: 318-320. 10.1038/ng0396-318.CrossRefPubMed
31.
Barash IA, Cheung CC, Weigle DS, Ren H, Kabigting EB, Kuijper JL, et al: Leptin is a metabolic signal to the reproductive system. Endocrinology. 1996, 137: 3144-3147. 10.1210/en.137.7.3144.PubMed
32.
Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, et al: Role of leptin in the neuroendocrine response to fasting. Nature. 1996, 382: 250-252. 10.1038/382250a0.CrossRefPubMed
33.
Mantzoros CS, Flier JS, Rogol AD: A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. V. Rising leptin levels may signal the onset of puberty. J Clin Endocrinol Metab. 1997, 82: 1066-1070. 10.1210/jc.82.4.1066.PubMed
34.
Mantzoros CS, Moschos SJ: Leptin: in search of role(s) in human physiology and pathophysiology. Clin Endocrinol (Oxf). 1998, 49: 551-567. 10.1046/j.1365-2265.1998.00571.x.CrossRef
35.
Licinio J, Negrao AB, Mantzoros C, Kaklamani V, Wong ML, Bongiorno PB, et al: Synchronicity of frequently sampled, 24-h concentrations of circulating leptin, luteinizing hormone, and estradiol in healthy women. Proc Natl Acad Sci USA. 1998, 95: 2541-2546. 10.1073/pnas.95.5.2541.CrossRefPubMedPubMedCentral
36.
Carro E, Senaris R, Considine RV, Casanueva FF, Dieguez C: Regulation of in vivo growth hormone secretion by leptin. Endocrinology. 1997, 138: 2203-2206. 10.1210/en.138.5.2203.CrossRefPubMed
37.
Paolisso G, Ammendola S, Del Buono A, Gambardella A, Riondino M, Tagliamonte MR, et al: Serum levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in healthy centenarians: relationship with plasma leptin and lipid concentrations, insulin action, and cognitive function. J Clin Endocrinol Metab. 1997, 82: 2204-2209. 10.1210/jc.82.7.2204.CrossRefPubMed
38.
Bruning PF, Van Doorn J, Bonfrer JM, Van Noord PA, Korse CM, Linders TC, et al: Insulin-like growth-factor-binding protein 3 is decreased in early-stage operable pre-menopausal breast cancer. Int J Cancer. 1995, 62: 266-270. 10.1002/ijc.2910620306.CrossRefPubMed
39.
Bohlke K, Cramer DW, Trichopoulos D, Mantzoros CS: Insulin-like growth factor-I in relation to premenopausal ductal carcinoma in situ of the breast. Epidemiology. 1998, 9: 570-573. 10.1097/00001648-199809000-00018.CrossRefPubMed
40.
Sierra-Honigmann MR, Nath AK, Murakami C, Garcia-Cardena G, Papapetropoulos A, Sessa WC, et al: Biological action of leptin as an angiogenic factor. Science. 1998, 281: 1683-1686. 10.1126/science.281.5383.1683.CrossRefPubMed
41.
Ribatti D, Nico B, Belloni AS, Vacca A, Roncali L, Nussdorfer GG: Angiogenic activity of leptin in the chick embryo chorioallantoic membrane is in part mediated by endogenous fibroblast growth factor-2. Int J Mol Med. 2001, 8: 265-268.PubMed
42.
Chagnon YC, Chung WK, Perusse L, Chagnon M, Leibel RL, Bouchard C: Linkages and associations between the leptin receptor (LEPR) gene and human body composition in the Quebec Family Study. Int J Obes Relat Metab Disord. 1999, 23: 278-286. 10.1038/sj.ijo.0800809.CrossRefPubMed
43.
Chagnon YC, Wilmore JH, Borecki IB, Gagnon J, Perusse L, Chagnon M, et al: Associations between the leptin receptor gene and adiposity in middle-aged Caucasian males from the HERITAGE family study. J Clin Endocrinol Metab. 2000, 85: 29-34. 10.1210/jc.85.1.29.PubMed
44.
Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 2005, 55: 74-108.CrossRefPubMed
Metadata
Title
Leptin receptor Gln223Arg polymorphism and breast cancer risk in Nigerian women: A case control study
Authors
Michael N Okobia
Clareann H Bunker
Seymour J Garte
Joseph M Zmuda
Emmanuel R Ezeome
Stanley N Anyanwu
Emmanuel E Uche
Lewis H Kuller
Robert E Ferrell
Emanuela Taioli
Publication date
01-12-2008
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2008
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-8-338

Other articles of this Issue 1/2008

BMC Cancer 1/2008 Go to the issue

Research article

Characterization of cells recovered from the xenotransplanted NG97 human-derived glioma cell line subcultured in a long-term in vitro

Research article

Endothelin receptor B antagonists decrease glioma cell viability independently of their cognate receptor

Research article

Validation of putative reference genes for gene expression studies in human hepatocellular carcinoma using real-time quantitative RT-PCR

Research article

Sequencing chemotherapy and radiotherapy in locoregional advanced breast cancer patients after mastectomy – a retrospective analysis

Research article

Association of the germline TP53R337H mutation with breast cancer in southern Brazil

Research article

High-resolution array CGH clarifies events occurring on 8p in carcinogenesis
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
Image Credits