胃食管反流及其他因素在食管腺癌进展过程中的作用
The Role of Gastroesophageal Reflux and Other Factors during Progression to Esophageal Adenocarcinoma.
作者信息
Hazelton William D, Curtius Kit, Inadomi John M, Vaughan Thomas L, Meza Rafael, Rubenstein Joel H, Hur Chin, Luebeck E Georg
机构信息
Program in Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Department of Applied Mathematics, University of Washington, Seattle, Washington.
出版信息
Cancer Epidemiol Biomarkers Prev. 2015 Jul;24(7):1012-23. doi: 10.1158/1055-9965.EPI-15-0323-T. Epub 2015 Apr 30.
BACKGROUND
U.S. esophageal adenocarcinoma (EAC) incidence increased over 5-fold between 1975 and 2009. Symptomatic gastroesophageal reflux disease (sGERD) elevates the risk for EAC. However, a simple calculation suggests that changes in sGERD prevalence can explain at most approximately 16% of this trend. Importantly, a mechanistic understanding of the influence of sGERD and other factors (OF) on EAC is lacking.
METHODS
A multiscale model was developed to estimate temporal trends for sGERD and OF, and their mechanistic role during carcinogenesis. Model calibration was to Surveillance, Epidemiology, and End Results (SEER) incidence and age-dependent sGERD data using maximum likelihood and Markov chain Monte Carlo (MCMC) methods.
RESULTS
Among men, 77.8% [95% credibility interval (CI), 64.9%-85.6%] of the incidence trend is attributable to OF, 13.4% (95% CI, 11.4%-17.3%) to sGERD, and 8.8% (95% CI, 4.2%-13.7%) to sGERD-OF interactions. Among women, 32.6% (95% CI, 27.0%-39.9%) of the trend is attributable to OF, 13.6% (95% CI, 12.5%-15.9%) to sGERD, and 47.4% (95% CI, 30.7%-64.6%) to interactions. The predicted trends were compared with historical trends for obesity, smoking, and proton pump inhibitor use. Interestingly, predicted OF cohort trends correlated most highly with median body mass index (BMI) at age 50 (r = 0.988 for men; r = 0.998 for women).
CONCLUSIONS
sGERD and OF mechanistically increase premalignant cell promotion, which increases EAC risk exponentially with exposure duration.
IMPACT
Surveillance should target individuals with long-duration sGERD and OF exposures.
背景
1975年至2009年间，美国食管腺癌（EAC）发病率增长了5倍多。症状性胃食管反流病（sGERD）会增加患EAC的风险。然而，简单计算表明，sGERD患病率的变化最多只能解释这一趋势的约16%。重要的是，目前尚缺乏对sGERD和其他因素（OF）对EAC影响的机制理解。
方法
开发了一个多尺度模型来估计sGERD和OF的时间趋势，以及它们在致癌过程中的机制作用。使用最大似然法和马尔可夫链蒙特卡罗（MCMC）方法，将模型校准到监测、流行病学和最终结果（SEER）发病率以及年龄相关的sGERD数据。
结果
在男性中，77.8%[95%可信区间（CI），64.9%-85.6%]的发病率趋势归因于OF，13.4%（95%CI，11.4%-17.3%）归因于sGERD，8.8%（95%CI，4.2%-13.7%）归因于sGERD与OF的相互作用。在女性中，32.6%（95%CI，27.0%-39.9%）的趋势归因于OF，13.6%（95%CI，12.5%-15.9%）归因于sGERD，47.4%（95%CI，30.7%-64.6%）归因于相互作用。将预测趋势与肥胖、吸烟和质子泵抑制剂使用的历史趋势进行了比较。有趣的是，预测的OF队列趋势与50岁时的中位体重指数（BMI）相关性最高（男性r = 0.988；女性r = 0.998）。
结论
sGERD和OF在机制上会增加癌前细胞的增殖，随着暴露时间的延长，EAC风险呈指数级增加。
影响
监测应针对长期暴露于sGERD和OF的个体。
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