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Abstract：
BACKGROUND: Colorectal cancer remains the second leading cause of cancer-related death in the US. As early-onset colorectal cancer (EO-CRC) becomes more prevalent in the US, research attention has shifted towards identifying at-risk populations. Previous studies have highlighted the rising rate of early-onset adenocarcinoma (ADC) and neuroendocrine tumors (NET) in the US. However, data on geographical variations of EO-CRC are scarce. Hence, our study aims to analyze time trends in EO-CRC incidence rates across various US regions and to assess these trends by sex and histopathological subtypes (ADC and NET).
METHODS: We analyze data spanning from 2001 to 2020 from the United States Cancer Statistics (USCS) database, covering nearly 98% of the US population. Using SEER*Stat software version (8.4.2, NCI), we calculated EO-CRC incidence rates among adults aged 20-54 years, adjusting for the age standard 2000 US population. The rates were categorized by sex and US geographical regions into west, midwest, northeast, and south. Time trends, reported as annual percentage change (APC) and average APC (AAPC), were generated via Joinpoint Regression software (v.5.0.2, NCI) utilizing the weighted Bayesian Information Criteria \"BIC\" method to generate the best-fit trends with a two-sided p-value cutoff at 0.05. The rates were also stratified by histopathology into ADC and NET.
RESULTS: Between 2001 and 2020, a total of 514,875 individuals were diagnosed with early-onset CRC in the US, with 54.78% being men. Incidence rates and trends varied across geographical regions. In the western region (comprising 106,685 patients, 54.85% men), incidence rates significantly increased in both women (AAPC = 1.37, p < 0.001) and men (AAPC = 1.34, p < 0.001). Similarly, in the midwestern region (with 110,380 patients, 55.46% men), there were significant increases in incidence rates among women (AAPC = 1.06, p < 0.001) and men (AAPC = 1.35, p < 0.001). The northeastern region (with 94,758 patients, 54.53% men) also witnessed significant increases in incidence rates for both women (AAPC = 0.71, p < 0.001) and men (AAPC = 0.84, p < 0.001). In contrast, the southern region (with 203,052 patients, 54.48% men) experienced slower increases in incidence rates among both women and men (AAPC = 0.25, p < 0.05 in women; AAPC = 0.66, p < 0.05 in men). When stratified by histopathology, incidence rates for adenocarcinomas (ADC) increased in all regions, most notably in the west (AAPC = 1.45, p < 0.05), and least in the south (AAPC = 0.46, p < 0.05). Conversely, for neuroendocrine tumors (NET), while incidence rates increased similarly across all regions, the pace was notably faster compared to ADC, particularly in the west (AAPC = 3.26, p < 0.05) and slower in the south (AAPC = 2.24, p < 0.05) Discussion: Our analysis of nationwide US data spanning two decades and encompassing over half a million early-onset CRC patients, representing nearly 98% of the US population, highlights significant temporal variation in incidence rates across various geographical regions. The most substantial increases in incidence rates were observed in the west, while the least pronounced changes were noted in the south, affecting both men and women. These trends persisted across the main CRC histopathological subtypes, with NET exhibiting a notably swifter pace of increase compared with ADC. These findings hold important implications for public health strategies and underscore the need for targeted interventions to address the rising burden of early-onset CRC across different regions in the US.
METHODS: We analyze data spanning from 2001 to 2020 from the United States Cancer Statistics (USCS) database, covering nearly 98% of the US population. Using SEER*Stat software version (8.4.2, NCI), we calculated EO-CRC incidence rates among adults aged 20-54 years, adjusting for the age standard 2000 US population. The rates were categorized by sex and US geographical regions into west, midwest, northeast, and south. Time trends, reported as annual percentage change (APC) and average APC (AAPC), were generated via Joinpoint Regression software (v.5.0.2, NCI) utilizing the weighted Bayesian Information Criteria \"BIC\" method to generate the best-fit trends with a two-sided p-value cutoff at 0.05. The rates were also stratified by histopathology into ADC and NET.
RESULTS: Between 2001 and 2020, a total of 514,875 individuals were diagnosed with early-onset CRC in the US, with 54.78% being men. Incidence rates and trends varied across geographical regions. In the western region (comprising 106,685 patients, 54.85% men), incidence rates significantly increased in both women (AAPC = 1.37, p < 0.001) and men (AAPC = 1.34, p < 0.001). Similarly, in the midwestern region (with 110,380 patients, 55.46% men), there were significant increases in incidence rates among women (AAPC = 1.06, p < 0.001) and men (AAPC = 1.35, p < 0.001). The northeastern region (with 94,758 patients, 54.53% men) also witnessed significant increases in incidence rates for both women (AAPC = 0.71, p < 0.001) and men (AAPC = 0.84, p < 0.001). In contrast, the southern region (with 203,052 patients, 54.48% men) experienced slower increases in incidence rates among both women and men (AAPC = 0.25, p < 0.05 in women; AAPC = 0.66, p < 0.05 in men). When stratified by histopathology, incidence rates for adenocarcinomas (ADC) increased in all regions, most notably in the west (AAPC = 1.45, p < 0.05), and least in the south (AAPC = 0.46, p < 0.05). Conversely, for neuroendocrine tumors (NET), while incidence rates increased similarly across all regions, the pace was notably faster compared to ADC, particularly in the west (AAPC = 3.26, p < 0.05) and slower in the south (AAPC = 2.24, p < 0.05) Discussion: Our analysis of nationwide US data spanning two decades and encompassing over half a million early-onset CRC patients, representing nearly 98% of the US population, highlights significant temporal variation in incidence rates across various geographical regions. The most substantial increases in incidence rates were observed in the west, while the least pronounced changes were noted in the south, affecting both men and women. These trends persisted across the main CRC histopathological subtypes, with NET exhibiting a notably swifter pace of increase compared with ADC. These findings hold important implications for public health strategies and underscore the need for targeted interventions to address the rising burden of early-onset CRC across different regions in the US.
摘要：
背景：结直肠癌仍然是美国癌症相关死亡的第二大原因。随着早发性结直肠癌（EO-CRC）在美国变得越来越普遍，研究的注意力已经转向识别高危人群。先前的研究强调了美国早发性腺癌（ADC）和神经内分泌肿瘤（NET）的发病率上升。然而,关于EO-CRC地理差异的数据很少。因此，我们的研究旨在分析美国各地区EO-CRC发病率的时间趋势,并按性别和组织病理学亚型(ADC和NET)评估这些趋势.
方法：我们分析了美国癌症统计（USCS）数据库中2001年至2020年的数据，覆盖了近98%的美国人口。使用SEER*Stat软件版本(8.4.2,NCI),我们计算了20-54岁成年人的EO-CRC发病率，根据2000年美国人口的年龄标准进行调整。这些比率按性别和美国地理区域分为西部，中西部,东北,和南方。时间趋势,报告为年度百分比变化(APC)和平均APC(AAPC)，通过Joinpoint回归软件（v.5.0.2，NCI）利用加权贝叶斯信息标准“BIC”方法生成最佳拟合趋势，双侧p值截止值为0.05。这些比率还通过组织病理学分层为ADC和NET。
结果：在2001年至2020年期间，美国共有514,875人被诊断为早发性CRC，54.78%是男性。发病率和趋势因地理区域而异。在西部地区（包括106,685名患者，54.85%男性)，女性(AAPC=1.37,p<0.001)和男性(AAPC=1.34,p<0.001)的发病率均显著增加.同样，在中西部地区(110,380名患者，55.46%男性)，女性(AAPC=1.06,p<0.001)和男性(AAPC=1.35,p<0.001)的发病率显著增加.东北地区（有94,758名患者，54.53％的男性）也见证了女性（AAPC=0.71，p<0.001）和男性（AAPC=0.84，p<0.001）的发病率显着增加。相比之下,南部地区（有203,052名患者，54.48％的男性）在女性和男性中的发病率均缓慢增加（女性AAPC=0.25，p<0.05；男性AAPC=0.66，p<0.05）。当通过组织病理学分层时，腺癌（ADC）的发病率在所有地区都有所增加，最值得注意的是在西部(AAPC=1.45，p<0.05)，和最小的南部（AAPC=0.46，p<0.05）。相反，神经内分泌肿瘤（NET），虽然所有地区的发病率都有类似的增长，与ADC相比，速度明显更快，特别是在西部（AAPC=3.26，p<0.05）和南部较慢（AAPC=2.24，p<0.05）讨论：我们对美国全国数据的分析跨越二十年，涵盖超过50万早发性CRC患者，占美国人口的近98%，突出了不同地理区域发病率的显著时间变化。发病率大幅度上升的是西部地区,虽然南方的变化最不明显，影响男人和女人。这些趋势在主要的CRC组织病理学亚型中持续存在，与ADC相比，NET表现出明显更快的增长速度。这些发现对公共卫生策略具有重要意义，并强调需要有针对性的干预措施，以解决美国不同地区早发CRC负担的上升。
方法：我们分析了美国癌症统计（USCS）数据库中2001年至2020年的数据，覆盖了近98%的美国人口。使用SEER*Stat软件版本(8.4.2,NCI),我们计算了20-54岁成年人的EO-CRC发病率，根据2000年美国人口的年龄标准进行调整。这些比率按性别和美国地理区域分为西部，中西部,东北,和南方。时间趋势,报告为年度百分比变化(APC)和平均APC(AAPC)，通过Joinpoint回归软件（v.5.0.2，NCI）利用加权贝叶斯信息标准“BIC”方法生成最佳拟合趋势，双侧p值截止值为0.05。这些比率还通过组织病理学分层为ADC和NET。
结果：在2001年至2020年期间，美国共有514,875人被诊断为早发性CRC，54.78%是男性。发病率和趋势因地理区域而异。在西部地区（包括106,685名患者，54.85%男性)，女性(AAPC=1.37,p<0.001)和男性(AAPC=1.34,p<0.001)的发病率均显著增加.同样，在中西部地区(110,380名患者，55.46%男性)，女性(AAPC=1.06,p<0.001)和男性(AAPC=1.35,p<0.001)的发病率显著增加.东北地区（有94,758名患者，54.53％的男性）也见证了女性（AAPC=0.71，p<0.001）和男性（AAPC=0.84，p<0.001）的发病率显着增加。相比之下,南部地区（有203,052名患者，54.48％的男性）在女性和男性中的发病率均缓慢增加（女性AAPC=0.25，p<0.05；男性AAPC=0.66，p<0.05）。当通过组织病理学分层时，腺癌（ADC）的发病率在所有地区都有所增加，最值得注意的是在西部(AAPC=1.45，p<0.05)，和最小的南部（AAPC=0.46，p<0.05）。相反，神经内分泌肿瘤（NET），虽然所有地区的发病率都有类似的增长，与ADC相比，速度明显更快，特别是在西部（AAPC=3.26，p<0.05）和南部较慢（AAPC=2.24，p<0.05）讨论：我们对美国全国数据的分析跨越二十年，涵盖超过50万早发性CRC患者，占美国人口的近98%，突出了不同地理区域发病率的显著时间变化。发病率大幅度上升的是西部地区,虽然南方的变化最不明显，影响男人和女人。这些趋势在主要的CRC组织病理学亚型中持续存在，与ADC相比，NET表现出明显更快的增长速度。这些发现对公共卫生策略具有重要意义，并强调需要有针对性的干预措施，以解决美国不同地区早发CRC负担的上升。
