阿司匹林或可降低肥胖个体的患癌风险

  发表于国际杂志Journal of Clinical Oncology上的一篇研究论文中，来自英国纽卡斯尔大学等处的研究人员通过研究发现，常规剂量的阿司匹林可以有效降低有家族史疾病的过重个体的长期患癌风险。该研究指出，过重会使得林奇综合征（Lynch Syndrome）患者患肠癌的风险加倍，林奇综合征是一种遗传性障碍，该疾病会影响机体中负责检测并且修复DNA损伤的基因的表达，大约一半患病个体都会患癌，主要为肠癌和子宫癌。
  研究者John Burn教授指出，通过近10年的研究我们发现常规剂量的阿司匹林或可降低家族史疾病个体的患癌风险，这对于林奇综合征患者尤为重要，同时过重个体或许也将因服用阿司匹林而获益。文章中研究者将炎性过程的增加同机体患癌风险增加关联了起来，肥胖会增加机体炎性反应，而研究者的一种解释为，阿司匹林或许可以抑制机体炎性，来为研究癌症发病起因提供思路。
  这项随机试验是CAPP2研究项目的一部分，CAPP2研究是来自全球16个国家的43个中心的科学家对将近1000名患林奇综合征的患者进行长达10年的研究项目；试验中研究者让937名参与者每天服用2粒阿司匹林（600mg）持续服用长达2年，同时设安慰剂组作为对照，当患者服用10年后，仅有55名患者发展为肠癌，而且其中肥胖个体患癌风险是正常体重个体的2.75倍。
  John Mathers博士说道，对于林奇综合征患者而言我们发现，在健康范围内BMI指数每增加一单位都会增加个体患肠癌风险7%；让我们非常好奇的是甚至在癌症遗传易感性个体中，肥胖依然是驱动个体患癌的风险，的确，相比一般个体而言，肥胖引发林奇综合征患者患癌的风险是前者的2倍。
  本文研究则阐明，每日常规剂量（600mg）阿司匹林的服用可以有效降低BMI指数较高个体的患癌风险，然而研究者还需要后期更多的深入研究来证实阿司匹林对机体患癌的降低影响。研究者表示，阿司匹林降低个体患癌风险的机制还需要进一步研究论证，实际上在个体机体开始出现肿瘤之前阿司匹林服用就已经产生了益处，而且这种效应会改变细胞在以后时间里患癌的风险。
  研究者也希望在人类研究中揭示阿司匹林发挥作用的机制，即阿司匹林可以对干细胞进行遗传性的损伤来使得癌细胞经历程序性细胞死亡进而抑制癌症恶化。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

Obesity, Aspirin, and Risk of Colorectal Cancer in Carriers of Hereditary Colorectal Cancer: A Prospective Investigation in the CAPP2 Study
JCO    doi: 10.1200/JCO.2014.58.9952
Mohammad Movahedi, D. Timothy Bishop, Finlay Macrae, Jukka-Pekka Mecklin, Gabriela Moeslein, Sylviane Olschwang, Diana Eccles, D. Gareth Evans, Eamonn R. Maher, Lucio Bertario, Marie-Luise Bisgaard, Malcolm G. Dunlop, Judy W.C. Ho, Shirley V. Hodgson, Annika Lindblom, Jan Lubinski, Patrick J. Morrison, Victoria Murday, Raj S. Ramesar, Lucy Side, Rodney J. Scott, Huw J.W. Thomas, Hans F. Vasen, John Burn and John C. Mathers⇑
Purpose In the general population, increased adiposity is a significant risk factor for colorectal cancer (CRC), but whether obesity has similar effects in those with hereditary CRC is uncertain. This prospective study investigated the association between body mass index and cancer risk in patients with Lynch syndrome (LS).

Patients and Methods Participants with LS were recruited to the CAPP2 study, in which they were randomly assigned to receive aspirin 600 mg per day or aspirin placebo, plus resistant starch 30 g per day or starch placebo (2 × 2 factorial design). Mean intervention period was 25.0 months, and mean follow-up was 55.7 months.

Results During follow-up, 55 of 937 participants developed CRC. For obese participants, CRC risk was 2.41× (95% CI, 1.22 to 4.85) greater than for underweight and normal-weight participants (reference group), and CRC risk increased by 7% for each 1-kg/m2 increase in body mass index. The risk of all LS-related cancers in obese people was 1.77× (95% CI, 1.06 to 2.96; P = .03) greater than for the reference group. In subgroup analysis, obesity was associated with 3.72× (95% CI, 1.41 to 9.81) greater CRC risk in patients with LS with MLH1 mutation, but no excess risk was observed in those with MSH2 or MSH6 mutation (P = .5). The obesity-related excess CRC risk was confined to those randomly assigned to the aspirin placebo group (adjusted hazard ratio, 2.75; 95% CI, 1.12 to 6.79; P = .03).

Conclusion Obesity is associated with substantially increased CRC risk in patients with LS, but this risk is abrogated in those taking aspirin. Such patients are likely to benefit from obesity prevention and/or regular aspirin.