Ritskes-Hoitinga J, Meijers M, Timmer W G, Wiersma A, Meijer G W, Weststrate J A
Department of Diet and Health Research, Unilever Research Laboratorium, Vlaardingen, The Netherlands.
Nutr Cancer. 1996;25(2):161-72. doi: 10.1080/01635589609514438.
The relationship between dietary fat intake (level and type) and the development of breast cancer in humans is a matter of concern in Western society. A high fat intake is associated with a greater mammary cancer risk in humans and in animal models. Higher intake of polyunsaturated fatty acids in humans shows little or no association with mammary tumor development in epidemiologic surveys. From literature data, it appears that a higher intake of polyunsaturated fatty acids (linoleic acid) is related to an increase in mammary tumorigenesis in animal studies in which chemical carcinogens like dimethylbenz[a]anthracene are used as tumor initiator. Mostly the latency period of these chemically induced models in rather short. In this study, the Bald/c-MMTV (mouse mammary tumor virus) mouse strain was chosen as an animal model: MMTV leads to tumor initiation, and dietary factors influence tumor promotion over a relatively long latency period. The mice were fed diets with two fat concentrations: a high [36% of energy (en%)] or low (16 en%) fat level; fat was isocalorically replaced by carbohydrates (cornstarch). At both dietary fat levels, linoleic acid was given at four levels: 2, 3, 6, and 10 en%. Linoleic acid-rich fat was isocalorically replaced by oleic acid-rich fat. The diets were consumed ad libitum over a lifetime. Animals were euthanized as soon as mammary tumor diameter was > or = 1 cm or when the animals were in a poor clinical condition. The incidence of mammary tumors at 18 months was significantly higher in one group only: 36 en% fat and 2 en% linoleic acid. This group also showed the shortest mean latency period for mammary tumor development. Mean mammary tumor incidence was higher and mean onset time shorter in the four high-fat groups than in the low-fat groups. No (linear) dose-response relationship between dietary linoleic acid concentration and mammary tumor incidence and latency period was observed. This indicates that a higher dietary linoleic acid intake does not increase the incidence or shorten the latency period of breast cancer in the Balb/c-MMTV mouse strain at two different dietary fat levels.
在西方社会，膳食脂肪摄入量（水平和类型）与人类乳腺癌发生之间的关系备受关注。高脂肪摄入与人类和动物模型中更高的乳腺癌风险相关。在流行病学调查中，人类较高的多不饱和脂肪酸摄入量与乳腺肿瘤发生几乎没有关联或没有关联。从文献数据来看，在使用二甲基苯并[a]蒽等化学致癌物作为肿瘤引发剂的动物研究中，较高的多不饱和脂肪酸（亚油酸）摄入量与乳腺肿瘤发生增加有关。这些化学诱导模型的潜伏期大多较短。在本研究中，选择Bald/c-MMTV（小鼠乳腺肿瘤病毒）小鼠品系作为动物模型：MMTV导致肿瘤起始，膳食因素在相对较长的潜伏期内影响肿瘤促进。给小鼠喂食两种脂肪浓度的饮食：高脂肪[能量的36%（en%）]或低脂肪（16 en%）水平；脂肪等热量地被碳水化合物（玉米淀粉）替代。在两种膳食脂肪水平下，亚油酸均以四个水平给予：2、3、6和10 en%。富含亚油酸的脂肪等热量地被富含油酸的脂肪替代。这些饮食在动物的一生中可随意食用。一旦乳腺肿瘤直径≥1 cm或动物处于临床状况不佳时，就对动物实施安乐死。仅在一组中，18个月时乳腺肿瘤的发生率显著更高：36 en%脂肪和2 en%亚油酸。该组还显示出乳腺肿瘤发生的平均潜伏期最短。四个高脂肪组的平均乳腺肿瘤发生率高于低脂肪组，且平均发病时间更短。未观察到膳食亚油酸浓度与乳腺肿瘤发生率和潜伏期之间的（线性）剂量反应关系。这表明在两种不同的膳食脂肪水平下，较高的膳食亚油酸摄入量不会增加Balb/c-MMTV小鼠品系中乳腺癌的发生率或缩短其潜伏期。
