Martin Christopher, Connelly Alexandra, Keku Temitope O, Mountcastle Sally B, Galanko Joseph, Woosley John T, Schliebe Barbara, Lund P Kay, Sandler Robert S
Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, 27599, USA.
Gastroenterology. 2002 Dec;123(6):1770-7. doi: 10.1053/gast.2002.37053.
BACKGROUND & AIMS: Observational studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of colorectal neoplasia. The mechanism of this effect could be via modification of apoptotic activity in colonic mucosa. We examined grossly normal rectal mucosa in patients with adenomas and adenoma-free controls to assess the associations between NSAID use, adenomatous polyps, and apoptosis.
Study participants were drawn from consecutive patients who underwent colonoscopy between August, 1998, and February, 2000. Biopsy specimens were taken from normal-appearing rectal mucosa 10 cm from the anal verge. Apoptosis was scored from coded, H&E-stained sections using morphologic methods. Proliferation was scored using whole crypt mitotic counts. Univariate and multivariate regression analyses were conducted to estimate crude and adjusted odds ratios (ORs).
There were 226 patients with adenomas and 493 adenoma-free controls. After adjusting for sex, age, race, and body mass index (BMI), individuals in the highest tertile of regular NSAID use were substantially less likely to have adenomas (OR 0.4; 95% CI: 0.2-0.7) compared with occasional or nonusers. Similarly, compared with the lowest tertile, persons in the highest tertile of rectal mucosal apoptotic activity were much less likely to have adenomas (OR 0.12; 95% CI: 0.07-0.20). NSAID use and apoptotic activity were not correlated (r = 0.10). Mucosal proliferation was not related to adenomas or NSAID use.
Our observations suggest that NSAID use and higher levels of mucosal apoptosis are independently associated with a lower prevalence of adenomas. The study shows a strong field effect for apoptosis.
观察性研究表明，非甾体抗炎药（NSAIDs）可降低结直肠肿瘤的风险。这种效应的机制可能是通过改变结肠黏膜中的凋亡活性。我们检查了腺瘤患者和无腺瘤对照者的大体正常直肠黏膜，以评估NSAIDs使用、腺瘤性息肉和凋亡之间的关联。
研究参与者来自1998年8月至2000年2月期间连续接受结肠镜检查的患者。从距肛门边缘10 cm处外观正常的直肠黏膜取活检标本。使用形态学方法从编码的苏木精-伊红（H&E）染色切片中对凋亡进行评分。使用全隐窝有丝分裂计数对增殖进行评分。进行单变量和多变量回归分析以估计粗比值比（OR）和调整后的比值比。
有226例腺瘤患者和493例无腺瘤对照者。在调整性别、年龄、种族和体重指数（BMI）后，与偶尔使用者或非使用者相比，经常使用NSAIDs处于最高三分位数的个体患腺瘤的可能性显著降低（OR 0.4；95%可信区间：0.2 - 0.7）。同样，与最低三分位数相比，直肠黏膜凋亡活性处于最高三分位数的人患腺瘤的可能性要低得多（OR 0.12；95%可信区间：0.07 - 0.20）。NSAIDs使用与凋亡活性无相关性（r = 0.10）。黏膜增殖与腺瘤或NSAIDs使用无关。
我们的观察结果表明，NSAIDs使用和较高水平的黏膜凋亡与腺瘤患病率较低独立相关。该研究显示了凋亡的强大场效应。
