Ong Kai Ren, Sims Andrew H, Harvie Michelle, Chapman Mary, Dunn Warwick B, Broadhurst David, Goodacre Royston, Wilson Mary, Thomas Nicola, Clarke Robert B, Howell Anthony
Breast Biology Group, School of Cancer and Imaging Sciences, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester M20 4BX, United Kingdom.
Cancer Prev Res (Phila). 2009 Aug;2(8):720-31. doi: 10.1158/1940-6207.CAPR-09-0008.
Dietary energy restriction (DER) reduces risk of spontaneous mammary cancer in rodents. In humans, DER in premenopausal years seems to reduce risk of postmenopausal breast cancer. Markers of DER are required to develop acceptable DER regimens for breast cancer prevention. We therefore examined markers of DER in the breast, adipose tissue, and serum. Nineteen overweight or obese women at moderately increased risk of breast cancer (lifetime risk, 1 in 6 to 1 in 3) ages between 35 and 45 were randomly allocated to DER [liquid diet, 3,656 kJ/d (864 kcal/d); n = 10] or asked to continue their normal eating patterns (n = 9) for one menstrual cycle. Biopsies of the breast and abdominal fat were taken before and after the intervention. RNA was extracted from whole tissues and breast epithelium (by laser capture microdissection) and hybridized to Affymetrix GeneChips. Longitudinal plasma and urine samples were collected before and after intervention, and metabolic profiles were generated using gas chromatography-mass spectrometry. DER was associated with significant reductions in weight [-7.0 (+/-2.3) kg] and in alterations of serum biomarkers of breast cancer risk (insulin, leptin, total and low-density lipoprotein cholesterol, and triglycerides). In both abdominal and breast tissues, as well as isolated breast epithelial cells, genes involved in glycolytic and lipid synthesis pathways (including stearoyl-CoA desaturase, fatty acid desaturase, and aldolase C) were significantly down-regulated. We conclude that reduced expressions of genes in the lipid metabolism and glycolytic pathways are detectable in breast tissue following DER, and these may represent targets for DER mimetics as effective chemoprophylactic agents.
饮食能量限制（DER）可降低啮齿动物自发性乳腺癌的风险。在人类中，绝经前进行饮食能量限制似乎可降低绝经后乳腺癌的风险。需要确定饮食能量限制的标志物，以制定可接受的预防乳腺癌的饮食能量限制方案。因此，我们检测了乳腺、脂肪组织和血清中饮食能量限制的标志物。19名年龄在35至45岁之间、患乳腺癌风险中度增加（终生风险为六分之一至三分之一）的超重或肥胖女性被随机分为两组，一组进行饮食能量限制（流食，3656千焦/天（864千卡/天）；n = 10），另一组被要求在一个月经周期内保持正常饮食模式（n = 9）。在干预前后对乳腺和腹部脂肪进行活检。从整个组织和乳腺上皮（通过激光捕获显微切割）中提取RNA，并与Affymetrix基因芯片杂交。在干预前后收集纵向血浆和尿液样本，并使用气相色谱-质谱法生成代谢谱。饮食能量限制与体重显著降低[-7.0（±2.3）千克]以及乳腺癌风险血清生物标志物（胰岛素、瘦素、总胆固醇和低密度脂蛋白胆固醇以及甘油三酯）的改变有关。在腹部和乳腺组织以及分离的乳腺上皮细胞中，参与糖酵解和脂质合成途径的基因（包括硬脂酰辅酶A去饱和酶、脂肪酸去饱和酶和醛缩酶C）均显著下调。我们得出结论，饮食能量限制后，乳腺组织中脂质代谢和糖酵解途径的基因表达降低，这些可能代表饮食能量限制模拟物作为有效的化学预防剂的靶点。
