Burn John, Bishop D Timothy, Mecklin Jukka-Pekka, Macrae Finlay, Möslein Gabriela, Olschwang Sylviane, Bisgaard Marie-Luise, Ramesar Raj, Eccles Diana, Maher Eamonn R, Bertario Lucio, Jarvinen Heikki J, Lindblom Annika, Evans D Gareth, Lubinski Jan, Morrison Patrick J, Ho Judy W C, Vasen Hans F A, Side Lucy, Thomas Huw J W, Scott Rodney J, Dunlop Malcolm, Barker Gail, Elliott Faye, Jass Jeremy R, Fodde Ricardo, Lynch Henry T, Mathers John C
Institute of Human Genetics, Newcastle University, International Centre for Life, Central Pkwy., Newcastle upon Tyne NE1 3BZ, United Kingdom.
N Engl J Med. 2008 Dec 11;359(24):2567-78. doi: 10.1056/NEJMoa0801297.
Observational and epidemiologic data indicate that the use of aspirin reduces the risk of colorectal neoplasia; however, the effects of aspirin in the Lynch syndrome (hereditary nonpolyposis colon cancer) are not known. Resistant starch has been associated with an antineoplastic effect on the colon.
In a randomized, placebo-controlled trial, we used a two-by-two design to investigate the effects of aspirin, at a dose of 600 mg per day, and resistant starch (Novelose), at a dose of 30 g per day, in reducing the risk of adenoma and carcinoma among persons with the Lynch syndrome.
Among 1071 persons in 43 centers, 62 were ineligible to participate in the study, 72 did not enter the study, and 191 withdrew from the study. These three categories were equally distributed across the study groups. Over a mean period of 29 months (range, 7 to 74), colonic adenoma or carcinoma developed in 141 participants. Of 693 participants randomly assigned to receive aspirin or placebo, neoplasia developed in 66 participants receiving aspirin (18.9%), as compared with 65 receiving placebo (19.0%) (relative risk, 1.0; 95% confidence interval [CI], 0.7 to 1.4). There were no significant differences between the two groups with respect to the development of advanced neoplasia (7.4% and 9.9%, respectively; P=0.33). Among the 727 participants receiving resistant starch or placebo, neoplasia developed in 67 participants receiving starch (18.7%), as compared with 68 receiving placebo (18.4%) (relative risk, 1.0; 95% CI, 0.7 to 1.4). Advanced adenomas and colorectal cancers were evenly distributed in the two groups. The prevalence of serious adverse events was low, and the events were evenly distributed.
The use of aspirin, resistant starch, or both for up to 4 years has no effect on the incidence of colorectal adenoma or carcinoma among carriers of the Lynch syndrome. (Current Controlled Trials number, ISRCTN59521990.)
观察性研究和流行病学数据表明，使用阿司匹林可降低结直肠肿瘤的风险；然而，阿司匹林对林奇综合征（遗传性非息肉病性结直肠癌）的影响尚不清楚。抗性淀粉已被证明对结肠具有抗肿瘤作用。
在一项随机、安慰剂对照试验中，我们采用2×2设计，研究每天服用600毫克阿司匹林和每天服用30克抗性淀粉（诺维糖）对降低林奇综合征患者腺瘤和癌风险的影响。
在43个中心的1071名受试者中，62名不符合参与研究的条件，72名未进入研究，191名退出研究。这三类情况在各研究组中分布均匀。在平均29个月（范围7至74个月）的时间里，141名参与者发生了结肠腺瘤或癌。在随机分配接受阿司匹林或安慰剂的693名参与者中，66名接受阿司匹林的参与者（18.9%）发生了肿瘤，而接受安慰剂的有65名（19.0%）（相对风险，1.0；95%置信区间[CI]，0.7至1.4）。两组在进展期肿瘤的发生方面无显著差异（分别为7.4%和9.9%；P = 0.33）。在接受抗性淀粉或安慰剂的727名参与者中，67名接受淀粉的参与者（18.7%）发生了肿瘤，而接受安慰剂的有68名（18.4%）（相对风险，1.0；95%CI，0.7至1.4）。进展期腺瘤和结直肠癌在两组中分布均匀。严重不良事件的发生率较低，且事件分布均匀。
长达4年使用阿司匹林、抗性淀粉或两者联合使用，对林奇综合征携带者的结直肠腺瘤或癌发病率无影响。（当前对照试验编号，ISRCTN59521990。）
