{"title":"IA02:结直肠癌","authors":"J. Carethers","doi":"10.1158/1538-7755.DISP17-IA02","DOIUrl":null,"url":null,"abstract":"Colorectal cancer (CRC) is the third most prevalent and second deadliest cancer in the U.S. with 135,430 cases and 50,260 deaths in 2017. Its pathogenesis stems from genetic susceptibility coupled with environmental interactions in the colon and rectum that synergize ideal conditions for neoplastic growth, initially from benign adenomatous polyps that might progress to carcinoma over several years. However, there is a disparity in morbidity and mortality among races, with African Americans demonstrating the highest incidence and mortality rates and a distribution of cancer that favors metastatic disease at presentation. The causes are likely multifactorial and include environmental factors that directly or indirectly influence the colonic epithelium and stem cells to be primed to commence the neoplastic process; societal factors such as socioeconomic class and access to health insurance; biologic factors such as earlier age development of adenomas and more proximal colon distribution of cancers or the gut microbiome; genetic factors such as higher frequency of somatic KRAS mutations that increase the aggressiveness of CRCs and shifts of the type of microsatellite instability that affect outcome; and immunologic factors such as less granzyme B-expressing T cells within CRCs. Most of these observations have just come in the past 10 years of research. Further biologic studies on environmental and genetic influences would be enhanced with adequate biorepository sources for CRC specimens from a variety of racial backgrounds, as most published data are not obtained from diverse specimens. CRC is preventable, and there is evidence that enhanced screening rates among African Americans can reduce or abolish the observed disparity. The 2017 U.S. Multi-Society Task Force on Colorectal Cancer for the first time included race as a factor in their screening recommendations, moving African Americans from age 50 years to age 45 years to commence CRC screening. Other opportunities to reduce the disparity include improved provider and patient education for screening and patient navigation for screening. Including a diverse population for trials of CRC screening, genome-wide association and other genetic studies, and treatment trials would further identify unique issues for higher-risk populations. Citation Format: John M. Carethers. Colorectal cancer [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. 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However, there is a disparity in morbidity and mortality among races, with African Americans demonstrating the highest incidence and mortality rates and a distribution of cancer that favors metastatic disease at presentation. The causes are likely multifactorial and include environmental factors that directly or indirectly influence the colonic epithelium and stem cells to be primed to commence the neoplastic process; societal factors such as socioeconomic class and access to health insurance; biologic factors such as earlier age development of adenomas and more proximal colon distribution of cancers or the gut microbiome; genetic factors such as higher frequency of somatic KRAS mutations that increase the aggressiveness of CRCs and shifts of the type of microsatellite instability that affect outcome; and immunologic factors such as less granzyme B-expressing T cells within CRCs. Most of these observations have just come in the past 10 years of research. 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引用次数: 0

摘要

结直肠癌(CRC)是美国第三大流行和第二致命的癌症,2017年有135,430例病例和50,260例死亡。其发病机制源于遗传易感性加上结肠和直肠的环境相互作用,这些环境相互作用协同了肿瘤生长的理想条件,最初是良性腺瘤性息肉,可能在几年内发展为癌。然而,不同种族的发病率和死亡率存在差异,非洲裔美国人的发病率和死亡率最高,癌症的分布倾向于转移性疾病。原因可能是多因素的,包括直接或间接影响结肠上皮细胞和干细胞启动肿瘤过程的环境因素;社会因素,如社会经济阶层和获得医疗保险的机会;生物因素,如腺瘤的早期发展和癌症或肠道微生物群的更近端结肠分布;遗传因素,如增加crc侵袭性的体细胞KRAS突变频率较高和影响预后的微卫星不稳定性类型的转移;和免疫因素,如红细胞中表达颗粒酶b的T细胞较少。这些观察结果大多是在过去10年的研究中得出的。由于大多数已发表的数据并非来自不同的标本,因此,如果有来自不同种族背景的结直肠癌标本的充足生物信息库来源,将加强对环境和遗传影响的进一步生物学研究。CRC是可以预防的,有证据表明,提高非裔美国人的筛查率可以减少或消除观察到的差异。2017年美国结直肠癌多社会工作组首次将种族作为筛查建议的一个因素,将非裔美国人从50岁提高到45岁,开始进行结直肠癌筛查。减少差距的其他机会包括改善提供者和患者对筛查的教育以及患者对筛查的指导。包括不同人群的CRC筛查试验,全基因组关联和其他基因研究,以及治疗试验将进一步确定高风险人群的独特问题。引文格式:John M. Carethers。结直肠癌[摘要]。见:第十届AACR会议论文集:种族/少数民族和医疗服务不足人群的癌症健康差异科学;2017年9月25-28日;亚特兰大,乔治亚州。费城(PA): AACR;癌症流行病学杂志,2018;27(7增刊):摘要nr - i02。
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Abstract IA02: Colorectal cancer
Colorectal cancer (CRC) is the third most prevalent and second deadliest cancer in the U.S. with 135,430 cases and 50,260 deaths in 2017. Its pathogenesis stems from genetic susceptibility coupled with environmental interactions in the colon and rectum that synergize ideal conditions for neoplastic growth, initially from benign adenomatous polyps that might progress to carcinoma over several years. However, there is a disparity in morbidity and mortality among races, with African Americans demonstrating the highest incidence and mortality rates and a distribution of cancer that favors metastatic disease at presentation. The causes are likely multifactorial and include environmental factors that directly or indirectly influence the colonic epithelium and stem cells to be primed to commence the neoplastic process; societal factors such as socioeconomic class and access to health insurance; biologic factors such as earlier age development of adenomas and more proximal colon distribution of cancers or the gut microbiome; genetic factors such as higher frequency of somatic KRAS mutations that increase the aggressiveness of CRCs and shifts of the type of microsatellite instability that affect outcome; and immunologic factors such as less granzyme B-expressing T cells within CRCs. Most of these observations have just come in the past 10 years of research. Further biologic studies on environmental and genetic influences would be enhanced with adequate biorepository sources for CRC specimens from a variety of racial backgrounds, as most published data are not obtained from diverse specimens. CRC is preventable, and there is evidence that enhanced screening rates among African Americans can reduce or abolish the observed disparity. The 2017 U.S. Multi-Society Task Force on Colorectal Cancer for the first time included race as a factor in their screening recommendations, moving African Americans from age 50 years to age 45 years to commence CRC screening. Other opportunities to reduce the disparity include improved provider and patient education for screening and patient navigation for screening. Including a diverse population for trials of CRC screening, genome-wide association and other genetic studies, and treatment trials would further identify unique issues for higher-risk populations. Citation Format: John M. Carethers. Colorectal cancer [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr IA02.
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