Colorectal Cancer Incidence Trends in the United States and United Kingdom: Evidence of Right- to Left-Sided Biological Gradients with Implications for Screening
Colorectal Cancer Incidence Trends in the United States and United Kingdom: Evidence of Right- to Left-Sided Biological Gradients with Implications for Screening
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DOI：
10.1158/0008-5472.can-09-4417
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发表时间：
2010-07-01
期刊：
影响因子：
11.2
通讯作者：
Luebeck, E. Georg
中科院分区：
文献类型：
--
作者：
Meza, Rafael;Jeon, Jihyoun;Luebeck, E. Georg
一些证据支持结肠镜筛查降低结直肠癌（CRC）发病率的前提，但对右侧和左侧肿瘤可能有不同的益处。为了更好地理解这种差异效应的生物学基础，我们推导了美国和英国人群中CRC发病率趋势的生物数学模型，分别代表了相对高患病率和低患病率的筛查。利用监测流行病学和最终结果（SEER）和国家统计局（ONS）登记处（1973-2006），我们推导了右侧（近端结肠）和左侧（远端结肠和直肠）肿瘤的随机多期克隆扩张（MSCE）模型。MSCE概念基于癌变的起始-促进-进展范式，并提供了从腺瘤起始（通过双等位基因肿瘤抑制基因失活）到CRC临床检测的自然肿瘤发展的定量描述。从1,228,036例（SEER: 340,582例；ONS: 887,454例）病例中，根据日历年和出生队列效应调整模型的参数估计显示，右侧肿瘤的腺瘤起始率更高，然而，矛盾的是，左侧肿瘤的腺瘤生长率更高。净效应是，只有70岁以后，右结肠患癌症的风险才会更高。与这一发现一致，腺瘤发展的模拟预测，随着年龄的增长，右侧和左侧肿瘤的相对患病率增加，这种差异在女性中最为显著。使用两个具有全国代表性的登记处对结直肠癌发展的现实生物数学描述，我们显示了右侧和左侧结直肠肿瘤的年龄和性别依赖的生物梯度。这些发现支持以年龄、性别和部位为导向的CRC筛查方法。癌症Res;70 (13);5419 - 29。(c) 2010年aacr。
Several lines of evidence support the premise that screening colonoscopy reduces colorectal cancer (CRC) incidence, but there may be differential benefits for right-and left-sided tumors. To better understand the biological basis of this differential effect, we derived biomathematical models of CRC incidence trends in U.S. and U.K. populations, representing relatively high-and low-prevalence screening, respectively. Using the Surveillance Epidemiology and End Results (SEER) and the Office for National Statistics (ONS) registries (both 1973-2006), we derived stochastic multistage clonal expansion (MSCE) models for right-sided (proximal colon) and left-sided (distal colon and rectal) tumors. The MSCE concept is based on the initiation-promotion-progression paradigm of carcinogenesis and provides a quantitative description of natural tumor development from the initiation of an adenoma (via biallelic tumor suppressor gene inactivation) to the clinical detection of CRC. From 1,228,036 (SEER: 340,582; ONS: 887,454) cases, parameter estimates for models adjusted for calendar-year and birth-cohort effects showed that adenoma initiation rates were higher for right-sided tumors, whereas, paradoxically, adenoma growth rates were higher for left-sided tumors. The net effect was a higher cancer risk in the right colon only after age 70 years. Consistent with this finding, simulations of adenoma development predicted that the relative prevalence for right-versus left-sided tumors increases with increasing age, a differential effect most striking in women. Using a realistic biomathematical description of CRC development for two nationally representative registries, we show age-and sex-dependent biological gradients for right-and left-sided colorectal tumors. These findings argue for an age-, sex-, and site-directed approach to CRC screening. Cancer Res; 70(13); 5419-29. (C) 2010 AACR.