根据BRAF突变状态,阿司匹林的使用和结直肠癌的风险
Reiko Nishihara1, Paul Lochhead, Aya Kuchiba
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
JAMA
|June 27, 2013
概括
定期使用阿司匹林可以降低患有BRAF野生型瘤但没有BRAF突变瘤的患者的结肠直肠癌风险. 这表明BRAF突变结肠细胞可能对阿司匹林敏感性较低,因此需要进一步调查临床影响.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 预防医学 预防医学
背景情况:
- 阿司匹林使用与降低结肠直肠癌风险有关.
- RAF类激酶可能会影响前列腺素-内氧化合成酶2 (PTGS2) 的表达.
- BRAF突变结直肠癌细胞可能对阿司匹林的作用敏感性降低.
研究的目的:
- 调查阿司匹林与结直肠癌风险的关联是否根据瘤BRAF瘤基因突变状态而有所不同.
- 为了比较阿司匹林在预防BRAF突变型与BRAF野生型瘤中的结直肠癌疗效.
主要方法:
- 使用来自护士健康研究和卫生专业人员随访研究数据的前性队列研究.
- 两年一次的调查问卷评估了阿司匹林的使用情况;参与者对癌症发病率和死亡率进行了跟踪.
- 考克斯比例危险回归模型被用来计算结直肠癌发病率的危险比,按BRAF突变状态分层.
主要成果:
- 定期使用阿司匹林与BRAF野生型结直肠癌的风险明显降低 (HR,0.73).
- 定期使用阿司匹林与BRAF突变结直肠癌的风险之间没有发现显著的关联 (HR,1.03;P异质性 = .037).
- 较高的阿司匹林摄入量 (>14片/周) 显示对BRAF野生型癌症具有更强的保护作用,风险因BRAF突变状态显著不同 (异质性的P = .005).
结论:
- 定期服用阿司匹林与BRAF野生型瘤患者的结直肠癌风险降低有关.
- 阿司匹林对结直肠癌的保护作用似乎在具有BRAF突变的瘤中减弱.
- 这些发现表明,基于BRAF突变状态,结肠瘤细胞对阿司匹林的潜在差异敏感性,这对个性化癌症预防策略有影响.
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