title: Circulating leptin, soluble leptin receptor, free leptin index, visfatin and selected leptin and leptin receptor gene polymorphisms in sporadic breast cancer.
abstract: Leptin and visfatin are implicated in breast cancer risk but studies accounting for bioavailability of leptin are sparse. Reports on the association of leptin gene (LEP) and leptin receptor gene (LEPR) polymorphisms with breast cancer are also inconsistent. Only a very few studies have examined biochemical and genetic variables concomitantly in the same cohort. A matched pairs study was carried out to ascertain whether plasma leptin, soluble leptin receptor, free leptin index (leptin/soluble leptin receptor), serum visfatin and selected LEP and LEPR polymorphisms are risk factors for sporadic breast cancer. Newly diagnosed sporadic breast cancer patients (N=80) were matched for age, body mass index (BMI) and menopausal status with healthy controls. Plasma leptin, soluble leptin receptor and serum visfatin were measured by enzyme-immunoassay. LEP -2548 A/G and LEPR K109R, LEPR Q223R polymorphisms were determined by genotyping. Leptin (p=0.0234), leptin/BMI (p=0.0468), free leptin index (p<0.0001) and visfatin (p=0.0002) were significantly higher and soluble leptin receptor (p<0.0001) was significantly lower in patients. LEPR gene K109R A/G polymorphism increased breast cancer risk (odds ratio: 4.125). Multivariate analysis confirmed that leptin, soluble leptin receptor, free leptin index and G109 (R109) allele of the LEPR gene K109R polymorphism are risk factors for breast cancer. When stratified by menopausal status free leptin index and soluble leptin receptor remained as risk factors irrespective of menopausal status while LEPR gene K109R A/G polymorphism remained as a risk factor only in the postmenopausal group.
authors.affiliation: Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo 03, 00300, Sri Lanka.
authors.forename: Chrishani
authors.initials: C
authors.lastname: Rodrigo
authors.affiliation: Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo 03, 00300, Sri Lanka.
authors.forename: Kamani Hemamala
authors.initials: KH
authors.lastname: Tennekoon
authors.affiliation: Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo 03, 00300, Sri Lanka.
authors.forename: Eric Hamilton
authors.initials: EH
authors.lastname: Karunanayake
authors.affiliation: National Cancer Institute, Maharagama 10280, Sri Lanka.
authors.forename: Kanishka
authors.initials: K
authors.lastname: De Silva
authors.affiliation: National Cancer Institute, Maharagama 10280, Sri Lanka.
authors.forename: Indrani
authors.initials: I
authors.lastname: Amarasinghe
authors.affiliation: Department of Community Medicine, Faculty of Medical Sciences, University of Sri Jayawardenapura, Nugegoda 10250, Sri Lanka.
authors.forename: Ananda
authors.initials: A
authors.lastname: Wijayasiri
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020738:Leptin / Q000097:blood* / Q000235:genetics*; D008593:Menopause / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D054409:Nicotinamide Phosphoribosyltransferase / Q000097:blood*; D020641:Polymorphism, Single Nucleotide; D054411:Receptors, Leptin / Q000097:blood* / Q000235:genetics*; D055815:Young Adult
chemical_list: D016207:Cytokines; D020738:Leptin; D054411:Receptors, Leptin; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human
keywords: Leptin; Leptin and leptin receptor gene polymorphism; Soluble leptin receptor; Sporadic breast cancer; Visfatin