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Open Access Highly Accessed Research article

Leptin and leptin receptor polymorphisms are associated with increased risk and poor prognosis of breast carcinoma

Kaouther Snoussi1, A Donny Strosberg2, Noureddine Bouaouina13, Slim Ben Ahmed4, A Noureddine Helal5 and Lotfi Chouchane1*

Author Affiliations

1 Laboratoire d'Immuno-Oncologie Moléculaire, Faculté de Médecine de Monastir, Université de Monastir, Tunisia

2 Department of Infectology, Scripps-Florida, USA

3 Department of Cancérologie Radiothérapie CHU Farhat Hached, Sousse, Tunisia

4 Department of Service de Carcinologie Médicale, CHU Farhat Hached, Sousse, Tunisia

5 Unité Génome, Diagnostic Immunitaire et Valorisation, Institut Supérieur de Biotechnologie de Monastir, Université de Monastir, Tunisia

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BMC Cancer 2006, 6:38  doi:10.1186/1471-2407-6-38

Published: 20 February 2006

Abstract

Background

Leptin (LEP) has been consistently associated with angiogenesis and tumor growth. Leptin exerts its physiological action through its specific receptor (LEPR). We have investigated whether genetic variations in LEP and LEPR have implications for susceptibility to and prognosis in breast carcinoma.

Methods

We used the polymerase chain reaction and restriction enzyme digestion to characterize the variation of the LEP and LEPR genes in 308 unrelated Tunisian patients with breast carcinoma and 222 healthy control subjects. Associations of the clinicopathologic parameters and these genetic markers with the rates of the breast carcinoma-specific overall survival (OVS) and the disease free survival (DFS) were assessed using univariate and multivariate analyses.

Results

A significantly increased risk of breast carcinoma was associated with heterozygous LEP (-2548) GA (OR = 1.45; P = 0.04) and homozygous LEP (-2548) AA (OR = 3.17; P = 0.001) variants. A highly significant association was found between the heterozygous LEPR 223QR genotype (OR = 1.68; P = 0.007) or homozygous LEPR 223RR genotype (OR = 2.26; P = 0.001) and breast carcinoma.

Moreover, the presence of the LEP (-2548) A allele showed a significant association with decreased disease-free survival in breast carcinoma patients, and the presence of the LEPR 223R allele showed a significant association with decreased overall survival.

Conclusion

Our results indicated that the polymorphisms in LEP and LEPR genes are associated with increased breast cancer risk as well as disease progress, supporting our hypothesis for leptin involvement in cancer pathogenesis.