據(jù)6月26日發(fā)表在《美國醫(yī)學(xué)會雜志》上的一則研究披露,，在2項(xiàng)大型的研究中，服用阿司匹林與罹患結(jié)腸直腸癌的風(fēng)險(xiǎn)之間的關(guān)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(jié)腸直腸癌風(fēng)險(xiǎn)的降低有關(guān),，但與變異型BRAF結(jié)腸直腸癌風(fēng)險(xiǎn)的降低無關(guān)；這些結(jié)果提示,，變異型BRAF結(jié)腸腫瘤細(xì)胞可能對阿司匹林的作用較不敏感,。
結(jié)腸直腸癌是全球與癌癥有關(guān)死亡的首要原因。根據(jù)文章的背景資料,，隨機(jī)對照的試驗(yàn)已經(jīng)證明服用阿司匹林可降低結(jié)腸直腸癌的風(fēng)險(xiǎn),。試驗(yàn)證據(jù)表明，與BRAF-野生型（即自然界發(fā)生的某個(gè)基因的典型形式）腫瘤細(xì)胞相比,，BRAF -變異的結(jié)腸細(xì)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(jù)BRAF的變異狀態(tài)對服用阿司匹林與結(jié)腸直腸癌風(fēng)險(xiǎn)的關(guān)系進(jìn)行了檢查。研究人員收集了在護(hù)士健康調(diào)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(guān)服用阿司匹林及跟蹤隨訪的參與者的兩年一次的問卷數(shù)據(jù),；對癌癥發(fā)病率的數(shù)據(jù)的收集一直到2006年7月,，對癌癥死亡率的數(shù)據(jù)的收集一直到2012年1月,。
在12萬7865個(gè)人中，發(fā)現(xiàn)有1226起直腸及結(jié)腸癌事件可以得到其分子生物學(xué)的數(shù)據(jù),。研究人員發(fā)現(xiàn),，常規(guī)服用阿司匹林與BRAF-野生型癌癥風(fēng)險(xiǎn)的顯著下降（27%）有關(guān)。常規(guī)服用阿司匹林與BRAF-變異型癌癥風(fēng)險(xiǎn)的降低沒有關(guān)系,。“服用阿司匹林與結(jié)腸直腸癌風(fēng)險(xiǎn)的關(guān)系會根據(jù)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(fēng)險(xiǎn)會隨著每周服用的阿司匹林片數(shù)的增加而降低；然而,，對BRAF-變異型癌而言卻沒有明顯的風(fēng)險(xiǎn)降低的趨勢,。 “每周服用阿司匹林的片數(shù)與患癌風(fēng)險(xiǎn)之間的關(guān)系隨著BRAF變異的狀態(tài)而有明顯的差異。與那些報(bào)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(fēng)險(xiǎn)有了顯著的下降,。”
此外，較長時(shí)間服用阿司匹林與BRAF野生型癌癥罹患風(fēng)險(xiǎn)的顯著下降有關(guān),，但服用阿司匹林的持續(xù)時(shí)間與BRAF變異型癌癥罹患風(fēng)險(xiǎn)沒有顯著的關(guān)系,。
“確認(rèn)可通過阿司匹林預(yù)防的特定癌癥亞型因?yàn)閿?shù)個(gè)原因而變的重要。首先,，它增進(jìn)了我們對結(jié)腸直腸腫瘤發(fā)病的分子機(jī)制以及阿司匹林可能發(fā)揮其抗腫瘤作用的機(jī)制的理解,。其次，研發(fā)對結(jié)腸直腸癌特定亞型的臨床的,、基因的或分子預(yù)測因子可能導(dǎo)致更有針對性的篩檢或可用化療進(jìn)行預(yù)防的策略的發(fā)展,。然而，鑒于不甚大的絕對風(fēng)險(xiǎn)差異,，有必要進(jìn)行進(jìn)一步的研究來評估我們的結(jié)果的臨床意義,。最后，我們的數(shù)據(jù)就服用阿司匹林與某種特定亞型的結(jié)腸直腸癌風(fēng)險(xiǎn)的降低之間存在著因果關(guān)系提供了額外的支持,。不斷累積的證據(jù)支持阿司匹林具有抗結(jié)腸直腸癌的預(yù)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.
