Llanos Adana A M, Brasky Theodore M, Mathew Jeena, Makambi Kepher H, Marian Catalin, Dumitrescu Ramona G, Freudenheim Jo L, Shields Peter G
The Ohio State University Comprehensive Cancer Center; RBHS-School of Public Health and the Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, New Jersey;
The Ohio State University Comprehensive Cancer Center; Division of Cancer Prevention and Control, College of Medicine, The Ohio State University, Columbus, Ohio;
Cancer Epidemiol Biomarkers Prev. 2014 Aug;23(8):1559-68. doi: 10.1158/1055-9965.EPI-14-0173. Epub 2014 May 13.
Circulating adipokines may be associated with breast cancer risk. Genetic variants governing adipokines and adipokine receptors may also predict risk, but their effect on breast adipokine concentrations is unknown.
We conducted a cross-sectional analysis of functional SNPs in 5 adipokine genes [adiponectin, leptin (LEP), and their receptors] among 85 cancer-free women who were undergoing reduction mammoplasty.
In multivariable-adjusted regression models, compared with the common GG genotype, the AA genotype of the LEP A19G SNP was associated with 27% lower plasma adiponectin [ratio, 0.73; 95% confidence interval (CI), 0.54-0.98] and leptin (ratio, 0.73; 95% CI, 0.55-0.96). Women with the AG genotype of LEP A19G had 39% lower breast leptin (ratio, 0.61; 95% CI, 0.39-0.97) compared with those with the GG genotype. No associations were observed for SNPs in the remaining genes.
Genetic variation in LEP may alter endogenous adipokine concentrations in circulation and in breast tissues.
These preliminary findings may support the hypothesis that genetic variation in adipokine genes modifies circulating adipokine concentrations and possibly leptin concentrations in local breast tissues, which may be associated with breast cancer risk.
循环中的脂肪因子可能与乳腺癌风险相关。调控脂肪因子及脂肪因子受体的基因变异也可能预测风险，但其对乳腺脂肪因子浓度的影响尚不清楚。
我们对85名接受缩乳术的无癌女性的5个脂肪因子基因（脂联素、瘦素及其受体）中的功能性单核苷酸多态性进行了横断面分析。
在多变量调整回归模型中，与常见的GG基因型相比，瘦素A19G单核苷酸多态性的AA基因型与血浆脂联素降低27%相关[比值，0.73；95%置信区间（CI），0.54 - 0.98]，与瘦素降低相关（比值，0.73；95% CI，0.55 - 0.96）。与GG基因型女性相比，瘦素A19G的AG基因型女性的乳腺瘦素降低39%（比值，0.61；95% CI，0.39 - 0.97）。其余基因的单核苷酸多态性未观察到相关性。
瘦素基因变异可能改变循环及乳腺组织中的内源性脂肪因子浓度。
这些初步发现可能支持以下假设，即脂肪因子基因变异可改变循环中的脂肪因子浓度，并可能改变局部乳腺组织中的瘦素浓度，这可能与乳腺癌风险相关。
