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


CONCLUSIONS
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.
Snoussi
Kaouther
K
Laboratoire d'Immuno-Oncologie Moléculaire, Faculté de Médecine de Monastir, Université de Monastir, Tunisia. naftikaouther@yahoo.fr
Strosberg
A Donny
AD
Bouaouina
Noureddine
N
Ben Ahmed
Slim
S
Helal
A Noureddine
AN
Chouchane
Lotfi
L
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020738:Leptin / Q000235:genetics*; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011110:Polymorphism, Genetic; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000235:genetics*; D054411:Receptors, Leptin; D018570:Risk Assessment; D014416:Tunisia
C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin