Mason Caitlin, Wang Lei, Duggan Catherine, Imayama Ikuyo, Thomas Sushma S, Wang Ching-Yun, Korde Larissa A, McTiernan Anne
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA USA.
Department of Biostatistics, University of Washington, Seattle, WA USA.
NPJ Breast Cancer. 2017 Apr 21;3:15. doi: 10.1038/s41523-017-0019-5. eCollection 2017.
Adipose tissue is involved in the etiology of postmenopausal breast cancer, possibly through increased sex steroid hormone production, inflammation, and altered adipokines. Vitamin D may affect these pathways but its effect on gene expression in different tissues has not been examined. Within a double-blind, 12-month placebo-controlled randomized trial, we compared 2000 IU/day oral vitamin D supplementation ( = 39) vs. placebo ( = 40) on the expression of 5 genes in breast and adipose tissue in overweight/obese postmenopausal women (50-75 years). All participants had serum 25-hydroxyvitamin D (25(OH)D) levels ≥ 10-<32 ng/mL ("insufficient") and concurrently completed a behavioral weight loss program. Random periareolar fine needle aspiration (RPFNA) and abdominal subcutaneous adipose tissue biopsies were performed at baseline and 12 months. Changes in expression of aromatase (), peroxisome proliferator-activated receptor gamma (), adiponectin (), monocyte-chemoattractant protein 1 (), and vitamin D receptor () were analyzed by qRT-PCR. Compared to placebo, 2000 IU vitamin D did not show significant effects on gene expression in breast or adipose tissue. Replete women (i.e., 25(OH)D ≥ 32 ng/mL; = 17) showed a small decrease in expression compared to an increase among women who remained 'insufficient' despite supplementation ( = 12) (Replete:-1.6% vs. Non-replete: 61.2%, = 0.015) in breast, but not adipose tissue. No statistically significant differences in gene expression were detected according to degree of weight loss. Vitamin D repletion during weight loss may have different effects on gene expression in breast and adipose tissue. Further research on the localized effects of vitamin D is needed to determine its effect on breast cancer risk.
脂肪组织参与绝经后乳腺癌的病因学，可能是通过增加性类固醇激素的产生、炎症反应以及改变脂肪因子来实现的。维生素D可能会影响这些途径，但其对不同组织中基因表达的影响尚未得到研究。在一项为期12个月的双盲、安慰剂对照随机试验中，我们比较了超重/肥胖绝经后妇女（50 - 75岁）每天口服2000国际单位维生素D补充剂（n = 39）与安慰剂（n = 40）对乳腺和脂肪组织中5种基因表达的影响。所有参与者的血清25 - 羟维生素D（25(OH)D）水平≥10 - <32 ng/mL（“不足”），并同时完成了一项行为减肥计划。在基线和12个月时进行随机乳晕周围细针穿刺（RPFNA）和腹部皮下脂肪组织活检。通过qRT - PCR分析芳香化酶（）、过氧化物酶体增殖物激活受体γ（）、脂联素（）、单核细胞趋化蛋白1（）和维生素D受体（）的表达变化。与安慰剂相比，2000国际单位维生素D对乳腺或脂肪组织中的基因表达没有显著影响。维生素D充足的女性（即25(OH)D≥32 ng/mL；n = 17）与补充后仍“不足”的女性（n = 12）相比，乳腺中 表达略有下降（充足组：-1.6% vs. 不充足组：61.2%，P = 0.015），但脂肪组织中没有。根据体重减轻程度未检测到基因表达的统计学显著差异。减肥期间补充维生素D可能对乳腺和脂肪组织中的基因表达有不同影响。需要进一步研究维生素D的局部作用，以确定其对乳腺癌风险的影响。
