2013年6月19日訊 /生物谷BIOON/--阿司匹林已知與一些癌症風險降低有關，最近一項新新的研究給出了一種解釋，由加州大學舊金山分校的科學家發現，阿司匹林能減慢癌前病變組織不正常細胞中DNA突變的積累。
阿司匹林和其他非甾體類消炎藥是常用的藥物，其成本效益。加州大學舊金山分校Carlo Maley博士說：阿司匹林預防癌症的效果可能是通過降低突變率。
這項研究公布6月13日的PLOS Genetics雜誌上，Maley與胃腸病學家和遺傳學家Brian Reid醫學博士分析了13例有巴雷特食道患者的活檢樣本，並進行6至19年的跟蹤研究。在「觀察交叉」（observational crossover）研究設計中，部分患者開始每日服用阿司匹林幾年後，然後停止服用，而其他人在首次觀察期間開始服用阿司匹林。研究人員的目標是追蹤不同時間帶你所採樣組織的突變率。
研究人員發現，服用阿司匹林的患者活檢比沒有服用阿司匹林的患者活檢組織基因突變的積累慢10倍以上。Maley說：這是第一次研究超過10年一直衡量患者惡性組織全基因組突變率，也是第一項評估阿司匹林怎麼影響那些突變率的研究。
癌症隨著時間的推移，突變累積。突變累積遠快於正常組織，在相同的腫瘤組織會出現不同的細胞群不同的突變。關鍵基因突變的獲得最終使腫瘤細胞生長失控，並導致腫瘤內的多樣性，形成耐藥性，這種現象是Maley研究的一大重點。
Maley推測阿司匹林降低突變率是由於藥物減少炎症的作用。炎症--免疫系統的應答，近年來已被確認為癌症的標誌。Maley說，較輕炎症可能會導致癌前病變組織內破壞DNA的氧化劑生成減少，並可能抑制生長刺激信號。Maley說，需要更多的研究以進一步探索非甾體類消炎藥與突變率和浸潤性癌發展之間的聯繫。（生物谷Bioon.com）
NSAIDs Modulate Clonal Evolution in Barrett's Esophagus
Rumen L. Kostadinov, Affiliations: Genomics and Computational Biology Graduate Program, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, The Wistar Institute, Philadelphia, Pennsylvania, United States of America, Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
Cancer is considered an outcome of decades-long clonal evolution fueled by acquisition of somatic genomic abnormalities (SGAs). Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce cancer risk, including risk of progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EA). However, the cancer chemopreventive mechanisms of NSAIDs are not fully understood. We hypothesized that NSAIDs modulate clonal evolution by reducing SGA acquisition rate. We evaluated thirteen individuals with BE. Eleven had not used NSAIDs for 6.2±3.5 (mean±standard deviation) years and then began using NSAIDs for 5.6±2.7 years, whereas two had used NSAIDs for 3.3±1.4 years and then discontinued use for 7.9±0.7 years. 161 BE biopsies, collected at 5–8 time points over 6.4–19 years, were analyzed using 1Million-SNP arrays to detect SGAs. Even in the earliest biopsies there were many SGAs (284±246 in 10/13 and 1442±560 in 3/13 individuals) and in most individuals the number of SGAs changed little over time, with both increases and decreases in SGAs detected. The estimated SGA rate was 7.8 per genome per year (95% support interval [SI], 7.1–8.6) off-NSAIDs and 0.6 (95% SI 0.3–1.5) on-NSAIDs. Twelve individuals did not progress to EA. In ten we detected 279±86 SGAs affecting 53±30 Mb of the genome per biopsy per time point and in two we detected 1,463±375 SGAs affecting 180±100 Mb. In one individual who progressed to EA we detected a clone having 2,291±78 SGAs affecting 588±18 Mb of the genome at three time points in the last three of 11.4 years of follow-up. NSAIDs were associated with reduced rate of acquisition of SGAs in eleven of thirteen individuals. Barrett's cells maintained relative equilibrium level of SGAs over time with occasional punctuations by expansion of clones having massive amount of SGAs.