Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK; VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, Belgium.
VIB Center for Brain and Disease Research, VIB, Leuven 3000, Belgium; Department of Microbiology and Immunology, KU Leuven-University of Leuven, Leuven 3000, Belgium.
Cell Rep. 2020 Jul 14;32(2):107880. doi: 10.1016/j.celrep.2020.107880.
Pancreatic cancer is a rare but fatal form of cancer, the fourth highest in absolute mortality. Known risk factors include obesity, diet, and type 2 diabetes; however, the low incidence rate and interconnection of these factors confound the isolation of individual effects. Here, we use epidemiological analysis of prospective human cohorts and parallel tracking of pancreatic cancer in mice to dissect the effects of obesity, diet, and diabetes on pancreatic cancer. Through longitudinal monitoring and multi-omics analysis in mice, we found distinct effects of protein, sugar, and fat dietary components, with dietary sugars increasing Mad2l1 expression and tumor proliferation. Using epidemiological approaches in humans, we find that dietary sugars give a MAD2L1 genotype-dependent increased susceptibility to pancreatic cancer. The translation of these results to a clinical setting could aid in the identification of the at-risk population for screening and potentially harness dietary modification as a therapeutic measure.
胰腺癌是一种罕见但致命的癌症，死亡率居第四位。已知的危险因素包括肥胖、饮食和 2 型糖尿病；然而，低发病率和这些因素的相互关联使得单独隔离个体效应变得复杂。在这里，我们使用前瞻性人类队列的流行病学分析和小鼠胰腺癌的平行追踪，来剖析肥胖、饮食和糖尿病对胰腺癌的影响。通过对小鼠进行纵向监测和多组学分析，我们发现了蛋白质、糖和脂肪膳食成分的不同影响，其中膳食糖会增加 Mad2l1 的表达和肿瘤增殖。通过对人类的流行病学方法，我们发现膳食糖使 Mad2l1 基因型依赖性增加了对胰腺癌的易感性。将这些结果转化到临床环境中，可以帮助确定高危人群进行筛查，并有可能利用饮食改变作为一种治疗措施。
