title: Plasma leptin levels, LEPR Q223R polymorphism and mammographic breast density: a cross-sectional study.
abstract: Obesity is associated with breast cancer in post-menopausal women, and breast density is a marker of breast cancer risk. Leptin is produced by the adipose tissue, acts through receptors that are polymorphic in nature, and is considered a cancer growth factor. The relationship between body mass index, leptin, leptin receptors and breast density is not well studied. A cross-sectional analysis in 392 post-menopausal healthy women was conducted; participants provided permission to obtain copies of their most recent screening mammogram. Non-fasting plasma leptin levels were determined using a commercially available leptin ELISA kit. Analysis of the Q223R genotypes of the LEPR gene were performed by PCR followed by restriction fragment length polymorphism analysis using DNA extracted from buffy coat samples. A statistically significant positive relationship was observed between leptin levels and body mass index (p<0.0001); leptin was significantly positively associated with mammography total breast area and non-dense breast area (p<0.0001), while it was inversely associated with percent breast density (p<0.0001). Leptin levels varied across the LEPR Q223R polymorphism, and were higher in women homozygous for the AA variant. Percent breast density decreased across the LEPR Q223R genotype, with lower percent density in women with the AA genotype. When dense area was considered according to quartiles of leptin and stratified by LEPR Q223R, a significant inverse trend between leptin levels and dense breast area was observed only among women with the G/G genotype (p-trend<0.001). After adjustment for possible confounders, leptin levels were significantly inversely associated with percent breast density (p=0.01). A significant interaction between body mass index and leptin levels on percent breast density was observed (p=0.03). These findings suggest that the association between leptin and breast density may vary by LEPR Q223R genotype, and that body mass index and leptin may act in an interactive way in determining breast density.
authors.affiliation: University of Pittsburgh, Department of Epidemiology, Graduate School of Public Health, Pittsburgh, PA, USA.
authors.forename: Cher
authors.initials: C
authors.lastname: Dallal
authors.forename: Seymour
authors.initials: S
authors.lastname: Garte
authors.forename: Camille
authors.initials: C
authors.lastname: Ragin
authors.forename: Jiangying
authors.initials: J
authors.lastname: Chen
authors.forename: Stacy
authors.initials: S
authors.lastname: Lloyd
authors.forename: Francesmary
authors.initials: F
authors.lastname: Modugno
authors.forename: Joel
authors.initials: J
authors.lastname: Weissfeld
authors.forename: Emanuela
authors.initials: E
authors.lastname: Taioli
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D000071060:Breast Density; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D003430:Cross-Sectional Studies; D055088:Early Detection of Cancer; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020738:Leptin / Q000097:blood* / Q000235:genetics; D042361:Mammary Glands, Human / Q000002:abnormalities*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054411:Receptors, Leptin / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C515448:LEPR protein, human; D020738:Leptin; D054411:Receptors, Leptin
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