• 在小鼠模型中,过度热量摄入/肥胖可驱动胰腺癌发生和生长,高蛋白饮食可推迟雌鼠胰腺癌发生,高脂(动物脂肪)饮食增加雄鼠胰腺癌死亡率;
  • 膳食葡萄糖可增加细胞周期检查点基因Mad2l1的表达,促进肿瘤细胞增殖,驱动胰腺癌的发生、生长和死亡率;
  • 对一项欧洲大型前瞻性队列中的46.5万人进行流行病学分析,发现膳食植物脂肪与胰腺癌风险降低相关;
  • 分析465名胰腺癌患者和5261名对照表明,膳食糖能增加MAD2L1基因突变者的胰腺癌风险。
《Cell Reports》发表的一项最新研究中,研究者结合小鼠实验和队列分析,探究了饮食与胰腺癌之间的互作关联,揭示了不同膳食成分对胰腺癌发生、生长和死亡率的复杂影响,鉴定出膳食糖与细胞周期检查点基因MAD2L1之间的互作关系在胰腺癌易感性中的作用,以及膳食植物脂肪的潜在保护性作用。这些发现或能帮助开发鉴定胰腺癌风险人群的筛查方法,并提示调节饮食或有助于胰腺癌的预防和治疗。
Cell Reports [IF:9.423]

Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer Susceptibility



2020-07-14, Article

Abstract & Authors:展开

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.

First Authors:
James Dooley

Correspondence Authors:
Inga Prokopenko,Peter Carmeliet,Adrian Liston

All Authors:
James Dooley,Vasiliki Lagou,Jermaine Goveia,Anna Ulrich,Katerina Rohlenova,Nathalie Heirman,Tobias Karakach,Yulia Lampi,Shawez Khan,Jun Wang,Tom Dresselaers,Uwe Himmelreich,Marc J Gunter,Inga Prokopenko,Peter Carmeliet,Adrian Liston