Impact of Family History of Colon Cancer on Adenomas in 40-49 Year Olds

描述(由申请人提供)： 背景：结直肠癌筛查的目的是通过在结肠镜检查中识别和切除晚期癌前息肉(即定义为腺瘤10 mm的晚期腺瘤、绒毛状腺瘤、伴有高度不典型增生的腺瘤)来预防癌症。学术团体和退伍军人管理局的最新指南对40-49岁有一级亲属(FDR)结直肠癌家族史的人进行结肠镜检查的必要性提出了不同的建议。我们假设，与年龄匹配的对照组相比，有结直肠癌家族史的40-49岁个体患晚期腺瘤的风险将增加。目的：(A)评估40-49岁有结直肠癌家族史的人中晚期腺瘤的绝对患病率，并将其与40-49岁有少量便血、腹部不适或肠道习惯改变(如便秘或腹泻)的“中等风险”个体的晚期腺瘤的绝对患病率进行比较；(B)使用多元Logistic回归分析确定40-49岁有结直肠癌家族史的人中与晚期腺瘤或腺瘤(任何大小)相关的危险因素。方法：这是一项多中心的前瞻性队列研究，在四个地点(安娜堡VAHS、达勒姆VAHS、密歇根卫生系统大学和马里兰州贝塞斯达的国家海军医学中心)进行。纳入标准：40-49岁因结直肠癌家族史而接受结肠镜检查的患者和40-49岁无结直肠癌家族史或结肠息肉家族史的患者接受结肠镜检查以评估少量便血、腹部不适或肠道习惯改变。[注：虽然结肠镜检查是评估这些症状的“标准护理”，但这些症状的出现与40-49岁人群中晚期腺瘤风险的增加无关。因此，在这些患者中结肠镜检查是合理的，并且这些患者代表了晚期腺瘤的“平均风险”人群。]在获得研究患者的知情同意后，我们将从结肠镜报告表格和息肉病理报告中收集息肉的大小、形态和位置的数据。研究患者还将完成腺瘤风险因素调查，该调查改编自美国国家癌症研究所的调查。患者对结直肠癌家族史的自我报告将被使用，因为已发表的文献显示该家族史自我报告的敏感性为86-93%，特异性为92-100%。这项研究的样本量被设定为1940名患者，如果晚期腺瘤的绝对患病率至少为4.0%，这将足以量化40-49岁有结直肠癌家族史的个体中晚期腺瘤的相对风险2.0。已获得试点资金，并已在两个地点开始招募患者。2009年8月31日，已有160名患者入选，招募人数增加到每周7-8名患者。 公共卫生相关性： 790万退伍军人在退伍军人管理局接受医疗保健。大约10%或790,000人与结直肠癌有一级亲属(FDR)。由于晚期腺瘤患病率增加，这些患者中是否应该在40岁时接受结肠镜检查？在40-49岁有这种家族史的人中，没有足够的前瞻性数据来回答这个问题。指南提供了关于这些患者在40岁或50岁时进行结肠镜检查的相互矛盾的建议，但指南强调，需要前瞻性数据来澄清建议。2007年退伍军人事务部CRC指令规定，60岁的FDR患者在40岁时必须接受结肠镜检查，但患有CRC&>60的FDR患者可能在40岁时接受结肠镜检查。VA内窥镜检查资源有限。这项研究将确定数十万退伍军人是否应该从40岁或50岁开始接受结肠镜检查。

DESCRIPTION (provided by applicant): IMPACT OF FAMILY HISTORY OF CRC ON ADENOMAS IN 40-49 YEAR OLDS BACKGROUND: The goal of CRC screening is to prevent cancer by identifying and removing advanced pre- cancerous polyps (i.e., advanced adenomas defined as adenomas > 10 mm, villous adenomas, adenomas with high-grade dysplasia) during colonoscopy. Current guidelines from academic societies and VA Directives provide different recommendations about the need to perform colonoscopy in 40-49 year olds with a family history of CRC in a first-degree relative (FDR). We hypothesize that 40-49 year old individuals with a family history of CRC will have an increased risk of advanced adenoma compared to age-matched controls. OBJECTIVES: (A) To estimate the absolute prevalence of advanced adenomas among 40-49 year old individuals with a family history of CRC and to compare this absolute prevalence versus the absolute prevalence of advanced adenomas in 40-49 year old "average-risk" individuals with scant hematochezia, abdominal discomfort, or altered bowel habits (i.e., constipation or diarrhea) as their indication for colonoscopy; (B) Identify risk factors associated with advanced adenomas or adenomas (any size) among 40-49 year old individuals with a family history of CRC using multiple logistic regression analysis. METHODS: This is a multi-center, prospective cohort study conducted at four sites (Ann Arbor VAHS, Durham VAHS, U. of Michigan Health System, and the National Naval Medical Center, Bethesda, MD). Inclusion criteria: 40-49 year old asymptomatic individuals referred for colonoscopy due to a family history of CRC AND 40-49 year old individuals without a family history of CRC or colon polyps who are referred for colonoscopy to evaluate scant hematochezia, abdominal discomfort or altered bowel habits. [Note: Although performance of colonoscopy is the "standard of care" to evaluate these symptoms, the presence of these symptoms is NOT associated with an increased risk of advanced adenomas in 40-49 year olds. Therefore, colonoscopy can be justified in these patients AND these patients represent an "average-risk" population for advanced adenomas.] After obtaining informed consent from study patients, we will gather data on the size, morphology, and location of polyps from colonoscopy report forms and polyp pathology reports. Study patients will also complete a risk factor survey for adenomas which has been adapted from a National Cancer Institute survey. Patient self-report of family history of CRC will be used since published literature demonstrates 86-93% sensitivity and 92-100% specificity for self-report of this family history. Sample size for this study has been set at 1940 patients which will be sufficient to quantify a relative risk of 2.0 for advanced adenomas in 40-49 year old individuals with a family history of CRC if the absolute prevalence of advanced adenomas is at least 4.0%. Pilot funding has been obtained, and patient recruitment has already been initiated at two sites. On August 31, 2009, 160 patients had been enrolled and recruitment has increased to 7-8 patients per week. PUBLIC HEALTH RELEVANCE: 7.9 million Veterans receive health care in the VA. Approximately 10% or 790,000 have a first-degree relative (FDR) with colorectal cancer (CRC). Should any of these patients undergo colonoscopy at age 40 due to an increased prevalence of advanced adenomas? There is not adequate prospective data in 40-49 year olds with this family history to answer this question. Guidelines provide conflicting recommendations about performing colonoscopy at age 40 or 50 in these patients, but guidelines emphasize that prospective data are needed to clarify recommendations. The 2007 VA CRC Directive states that individuals with a FDR with CRC <60 years old are to get colonoscopy at age 40, but individuals with a FDR with CRC > 60 may get colonoscopy at age 40. VA endoscopic resources are limited. This study will determine if hundreds of thousands of Veterans should get colonoscopy starting at age 40 or age 50.