Regular Aspirin Use Associates With Lower Risk of Colorectal Cancers With Low Numbers of Tumor-Infiltrating Lymphocytes.
Regular Aspirin Use Associates With Lower Risk of Colorectal Cancers With Low Numbers of Tumor-Infiltrating Lymphocytes.
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DOI：
10.1053/j.gastro.2016.07.030
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发表时间：
2016-11
期刊：
影响因子：
29.4
通讯作者：
Ogino S
中科院分区：
文献类型：
--
作者：
Cao Y;Nishihara R;Qian ZR;Song M;Mima K;Inamura K;Nowak JA;Drew DA;Lochhead P;Nosho K;Morikawa T;Zhang X;Wu K;Wang M;Garrett WS;Giovannucci EL;Fuchs CS;Chan AT;Ogino S
服用阿司匹林可降低结直肠癌风险。阿司匹林是一种非甾体抗炎药，可抑制PTGS 2（环氧合酶-2）; PTGS 2可促进炎症并抑制T细胞介导的适应性免疫。我们研究了阿司匹林使用与结直肠癌风险的负相关性是否在淋巴细胞浸润程度较低的肿瘤中比在淋巴细胞浸润程度较高的肿瘤中更强。我们每两年从护士健康研究和健康专业人员随访研究的参与者中收集阿司匹林使用数据。参与者被问及他们是否在大多数星期服用阿司匹林，每周服用的药片数量以及阿司匹林使用的年份。我们从美国的病理学实验室收集了可用的肿瘤标本（n=1458）。病理学家确认了结直肠腺癌（不包括肛门鳞状细胞癌）的诊断，并评价了组织病理学特征，包括肿瘤区域内和周围淋巴细胞浸润的模式和程度。随访人-年从问卷返回之日起累积，直至结直肠癌诊断、死亡或随访结束（2010年6月）。重复方法考克斯比例风险回归被用来评估阿司匹林与结直肠癌发病率的关系，根据肿瘤浸润淋巴细胞（TILs），肿瘤内腺周反应，肿瘤周围反应或克罗恩样反应的程度进行亚组划分。我们记录了1458例直肠癌和结肠癌。定期使用阿司匹林与结直肠癌风险之间的负相关性因TIL浓度而显着不同（P异质性=0.007）。与不定期使用相比，定期使用阿司匹林与低水平TLR的肿瘤风险较低相关（相对风险，0.72; 95%CI，0.63-0.81）;这种关联的强度取决于阿司匹林剂量和持续时间（均P趋势<0.001）。相比之下，阿司匹林的使用与具有中等或高水平TIL的肿瘤的风险无关。无论肿瘤微卫星不稳定性、BRAF突变或PTGS 2表达的状态如何，这种差异相关性都是一致的。定期使用阿司匹林与低水平的CD 3 + T细胞、CD 8 + T细胞或CD 45 RO（PTPRC）+ T细胞（通过免疫组织化学和计算机辅助图像分析测量）的肿瘤风险较低相关。根据前瞻性队列研究的数据，定期使用阿司匹林与低浓度TIL的结直肠癌风险降低相关。这些发现表明，肿瘤微环境中的免疫反应可能参与阿司匹林的化学预防作用。
Aspirin use reduces colorectal cancer risk. Aspirin, a nonsteroidal anti-inflammatory drug, inhibits PTGS2 (cyclooxygenase-2); PTGS2 promotes inflammation and suppresses T cell-mediated adaptive immunity. We investigated whether the inverse association of aspirin use with colorectal carcinoma risk was stronger for tumors with lower degrees of lymphocytic infiltrates than for tumors with higher degrees of lymphocytic infiltrates. We collected aspirin use data biennially from participants in the Nurses’ Health Study and Health Professionals Follow-up Study. Participants were asked whether they took aspirin in most weeks, the number of tablets taken per week, and years of aspirin use. We collected available tumor specimens (n=1458) from pathology laboratories in the US. A pathologist confirmed the diagnosis of colorectal adenocarcinoma (excluding anal squamous cell carcinoma), and evaluated histopathology features, including patterns and degrees of lymphocytic infiltrates within and around tumor areas. Person-years of follow-up were accrued from the date of return of questionnaires until dates of colorectal cancer diagnosis, death, or the end of follow-up (June 2010). Duplication-method Cox proportional hazards regression was used to assess the association of aspirin with incidence of colorectal carcinoma subgroups according to the degree of tumor-infiltrating lymphocytes (TILs), intratumoral periglandular reaction, peritumoral reaction, or Crohn’s-like reaction. We documented 1458 rectal and colon cancers. The inverse association between regular aspirin use and colorectal cancer risk significantly differed by concentrations of TILs (Pheterogeneity =0.007). Compared with nonregular use, regular aspirin use was associated with a lower risk of tumors that had low levels of TILs (relative risk, 0.72; 95% CI, 0.63–0.81); strength of the association depended on aspirin dose and duration (both Ptrend <0.001). In contrast, aspirin use was not associated with a risk of tumors having intermediate or high levels TILs. This differential association was consistent regardless of status of tumor microsatellite instability, mutations in BRAF, or expression of PTGS2. Regular aspirin use was associated with a lower risk of tumors that contained low levels of CD3+ T cells, CD8+ T cells, or CD45RO (PTPRC)+ T cells (measured by immunohistochemistry and computer-assisted image analysis). Based on data from the prospective cohort studies, regular use of aspirin is associated with a lower risk of colorectal carcinomas with low concentrations of TILs. These findings indicate that the immune response in the tumor microenvironment could be involved in the chemopreventive effects of aspirin.
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功能表达克隆将COX-2鉴定为抗原特异性癌症免疫的抑制剂。
影响因子：
9
作者：
Göbel C;Breitenbuecher F;Kalkavan H;Hähnel PS;Kasper S;Hoffarth S;Merches K;Schild H;Lang KS;Schuler M
通讯作者：
Schuler M
诊断后使用阿司匹林而不是诊断前使用阿司匹林可以改善已确定的结直肠癌生存率：一项荟萃分析。
影响因子：
24.5
作者：
Li, Peiwei;Wu, Han;Wu, Yihua
通讯作者：
Wu, Yihua
影响因子：
28.2
作者：
Llosa, Nicolas J.;Cruise, Michael;Housseau, Franck
通讯作者：
Housseau, Franck
结直肠癌的免疫基因组分层：对靶向免疫疗法发展的影响。
影响因子：
7.2
作者：
Lal N;Beggs AD;Willcox BE;Middleton GW
通讯作者：
Middleton GW
DOI：
10.1158/1940-6207.capr-13-0036
发表时间：
2013-08
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Marzbani E;Inatsuka C;Lu H;Disis ML
通讯作者：
Disis ML