University of Pittsburgh, Department of Epidemiology, Graduate School of Public Health, Pittsburgh, PA, USA.
Int J Biol Markers. 2013 Jun 28;28(2):161-7. doi: 10.5301/jbm.5000016.
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.
肥胖与绝经后妇女的乳腺癌有关，而乳腺密度是乳腺癌风险的一个标志物。瘦素由脂肪组织产生，通过自然多态性的受体发挥作用，被认为是一种癌症生长因子。体重指数、瘦素、瘦素受体与乳腺密度之间的关系尚未得到很好的研究。对 392 名绝经后健康女性进行了横断面分析；参与者同意获得其最近的乳房 X 光筛查的复印件。使用市售的瘦素 ELISA 试剂盒测定非禁食状态下的血浆瘦素水平。使用从白细胞样本中提取的 DNA 通过 PCR 分析 LEPR 基因的 Q223R 基因型，然后进行限制片段长度多态性分析。观察到瘦素水平与体重指数之间存在显著的正相关关系（p<0.0001）；瘦素与乳房 X 光摄影总乳腺面积和非致密乳腺面积显著正相关（p<0.0001），而与乳腺密度百分比呈负相关（p<0.0001）。瘦素水平在 LEPR Q223R 多态性中有所不同，在 AA 变异纯合子女性中更高。乳腺密度百分比随 LEPR Q223R 基因型而变化，AA 基因型女性的乳腺密度百分比较低。当根据瘦素的四分位数考虑致密区，并按 LEPR Q223R 分层时，仅在 G/G 基因型女性中观察到瘦素水平与致密乳腺区之间存在显著的负趋势（p 趋势<0.001）。在调整了可能的混杂因素后，瘦素水平与乳腺密度百分比呈显著负相关（p=0.01）。还观察到体重指数和瘦素水平对乳腺密度百分比的显著交互作用（p=0.03）。这些发现表明，瘦素与乳腺密度之间的关联可能因 LEPR Q223R 基因型而异，并且体重指数和瘦素可能以相互作用的方式作用于确定乳腺密度。
