據6月26日發(fā)表在《美國醫(yī)學會雜志》上的一則研究披露,，在2項大型的研究中,，服用阿司匹林與罹患結腸直腸癌的風險之間的關系受到了BRAF基因突變的影響，常規(guī)服用阿司匹林與野生型BRAF結腸直腸癌風險的降低有關,，但與變異型BRAF結腸直腸癌風險的降低無關,；這些結果提示，變異型BRAF結腸腫瘤細胞可能對阿司匹林的作用較不敏感,。
結腸直腸癌是全球與癌癥有關死亡的首要原因,。根據文章的背景資料，隨機對照的試驗已經證明服用阿司匹林可降低結腸直腸癌的風險,。試驗證據表明,，與BRAF-野生型（即自然界發(fā)生的某個基因的典型形式）腫瘤細胞相比，BRAF -變異的結腸細胞可能對阿司匹林的抗腫瘤作用較不敏感,。
波士頓Dana-Farber癌癥研究所的Reiko Nishihara, Ph.D.及其同事根據BRAF的變異狀態(tài)對服用阿司匹林與結腸直腸癌風險的關系進行了檢查,。研究人員收集了在護士健康調查（從1980年開始）及衛(wèi)生專業(yè)人員隨訪研究（從1986年開始）中的有關服用阿司匹林及跟蹤隨訪的參與者的兩年一次的問卷數據,；對癌癥發(fā)病率的數據的收集一直到2006年7月，對癌癥死亡率的數據的收集一直到2012年1月,。
在12萬7865個人中,，發(fā)現有1226起直腸及結腸癌事件可以得到其分子生物學的數據。研究人員發(fā)現,，常規(guī)服用阿司匹林與BRAF-野生型癌癥風險的顯著下降（27%）有關,。常規(guī)服用阿司匹林與BRAF-變異型癌癥風險的降低沒有關系。“服用阿司匹林與結腸直腸癌風險的關系會根據BRAF的變異狀態(tài)而有明顯的差異,。”
文章的作者還觀察到BRAF-野生型癌癥的罹患風險會隨著每周服用的阿司匹林片數的增加而降低,；然而，對BRAF-變異型癌而言卻沒有明顯的風險降低的趨勢,。 “每周服用阿司匹林的片數與患癌風險之間的關系隨著BRAF變異的狀態(tài)而有明顯的差異,。與那些報告沒有服用阿司匹林者相比，在那些每周服用6-14片阿司匹林的人中及在那些每周服用超過14片阿司匹林的人中觀察到的罹患BRAF野生型癌癥風險有了顯著的下降,。”
此外,，較長時間服用阿司匹林與BRAF野生型癌癥罹患風險的顯著下降有關，但服用阿司匹林的持續(xù)時間與BRAF變異型癌癥罹患風險沒有顯著的關系,。
“確認可通過阿司匹林預防的特定癌癥亞型因為數個原因而變的重要,。首先，它增進了我們對結腸直腸腫瘤發(fā)病的分子機制以及阿司匹林可能發(fā)揮其抗腫瘤作用的機制的理解,。其次,，研發(fā)對結腸直腸癌特定亞型的臨床的、基因的或分子預測因子可能導致更有針對性的篩檢或可用化療進行預防的策略的發(fā)展,。然而,，鑒于不甚大的絕對風險差異，有必要進行進一步的研究來評估我們的結果的臨床意義,。最后,，我們的數據就服用阿司匹林與某種特定亞型的結腸直腸癌風險的降低之間存在著因果關系提供了額外的支持。不斷累積的證據支持阿司匹林具有抗結腸直腸癌的預防作用,。”（生物谷Bioon.com）
生物谷推薦英文摘要
JAMA doi:10.1001/jama.2013.6599.
Aspirin Use and Risk of Colorectal Cancer According to BRAF Mutation Status
Importance Aspirin use reduces the risk of colorectal carcinoma. Experimental evidence implicates a role of RAF kinases in up-regulation of prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase 2), suggesting that BRAF-mutant colonic cells might be less sensitive to the antitumor effects of aspirin than BRAF–wild-type neoplastic cells.
Objective To examine whether the association of aspirin intake with colorectal cancer risk differs according to status of tumor BRAF oncogene mutation.
Design and Setting We collected biennial questionnaire data on aspirin use and followed up participants in the Nurses' Health Study (from 1980) and the Health Professionals Follow-up Study (from 1986) until July 1, 2006, for cancer incidence and until January 1, 2012, for cancer mortality. Duplication-method Cox proportional cause-specific hazards regression for competing risks data was used to compute hazard ratios (HRs) for colorectal carcinoma incidence according to BRAF mutation status.
Main Outcomes and Measures Incidence of colorectal cancer cases according to tumor BRAF mutation status.
Results Among 127 865 individuals, with 3 165 985 person-years of follow-up, we identified 1226 incident rectal and colon cancers with available molecular data. Compared with nonuse, regular aspirin use was associated with lower BRAF–wild-type cancer risk (multivariable HR, 0.73; 95% CI, 0.64 to 0.83; age-adjusted incidence rate difference [RD], ?9.7; 95% CI, ?12.6 to ?6.7 per 100 000 person-years). This association was observed irrespective of status of tumor PTGS2 expression or PIK3CA or KRAS mutation. In contrast, regular aspirin use was not associated with a lower risk of BRAF-mutated cancer (multivariable HR, 1.03; 95% CI, 0.76 to 1.38; age-adjusted, incidence RD, 0.7; 95% CI, ?0.3 to 1.7 per 100 000 person-years: P for heterogeneity = .037, between BRAF–wild-type vs BRAF-mutated cancer risks). Compared with no aspirin use, aspirin use of more than 14 tablets per week was associated with a lower risk of BRAF–wild-type cancer (multivariable HR, 0.43; 95% CI, 0.25 to 0.75; age-adjusted incidence RD, ?19.8; 95% CI, ?26.3 to ?13.3 per 100 000 person-years). The relationship between the number of aspirin tablets per week and colorectal cancer risk differed significantly by BRAF mutation status (P for heterogeneity = .005).
Conclusions and Relevance Regular aspirin use was associated with lower risk of BRAF–wild-type colorectal cancer but not with BRAF-mutated cancer risk. These findings suggest that BRAF-mutant colon tumor cells may be less sensitive to the effect of aspirin. Given the modest absolute risk difference, further investigations are necessary to determine clinical implications of our findings.
