Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives
Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives
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DOI：
10.1097/gim.0b013e31818fa2ff
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发表时间：
2009-01-01
影响因子：
8.8
通讯作者：
Teutsch, Steven
中科院分区：
文献类型：
--
作者：
Berg, Alfred O.;Grp, E. G. A. P. P. Working;Teutsch, Steven
建议：基因组在实践和预防中的应用评估 (EGAPP) 工作组发现了足够的证据，建议为新诊断的结直肠癌患者提供林奇综合征基因检测，以降低亲属的发病率和死亡率。我们发现没有足够的证据来推荐在几项检查中采用特定的基因检测策略。 理由：建议对新诊断的结直肠癌 (CRC) 个体进行基因检测以检测林奇综合征，作为降低其亲属的 CRC 发病率和死亡率的策略（有关林奇综合征的定义，请参阅临床注意事项部分）。 EGAPP 工作组 (EWG) 构建了一系列证据，将新诊断的 CRC 患者的林奇综合征基因检测与其亲属的健康状况改善联系起来。我们发现，通过一系列基因检测对新诊断的结直肠癌患者进行评估可能会导致林奇综合征的识别。然后可以为林奇综合征患者的亲属提供基因检测，并在有需要时进行结直肠癌和可能的子宫内膜癌监测，以期改善健康结果。专家工作组的结论是，这种测试策略一定会带来一定的人口效益。分析有效性：专家工作组找到了足够的证据来得出结论，初步测试和诊断测试的分析灵敏度和特异性很高。临床有效性：在考虑了所使用的具体技术和标记数量后，专家工作组至少找到了足够的证据来描述三项初步测试以及四项选定测试策略的临床敏感性和特异性。这些临床有效性的衡量标准因每次测试和每种策略而异（参见临床注意事项部分）。临床实用性：EWG 发现了足够的证据来测试接受率、对推荐监测活动的遵守情况、可接近的亲属数量、与额外随访相关的危害以及常规结肠镜检查的有效性。这一系列证据支持使用基因检测策略来降低林奇综合征亲属的发病率/死亡率。几种基因检测策略可能有效，但没有一个明显优越。支持或反对识别错配修复（MMR）基因突变在降低子宫内膜癌发病率或死亡率方面的有效性的证据并不充分。背景问题：CRC 是一种常见疾病，2007 年美国估计有 52,000 人死亡。在新诊断的 CRC 中，约 3% 的根本原因是 MMR 基因（林奇综合征）突变，可以通过现有的实验室测试可靠地识别出该突变。遗传该突变的亲属患结直肠癌的风险很高（70 岁时约为 45%）。有证据表明，这些亲属通常会接受检测和加强监视。
Of Recommendations: The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group found sufficient evidence to recommend offering genetic testing for Lynch syndrome to individuals with newly diagnosed colorectal cancer to reduce morbidity and mortality in relatives. We found insufficient evidence to recommend a specific genetic testing strategy among the several examined.Rationale: Genetic testing to detect Lynch syndrome in individuals with newly diagnosed colorectal cancer (CRC) is proposed as a strategy to reduce CRC morbidity and mortality in their relatives (see Clinical Considerations section for definition of Lynch syndrome). The EGAPP Working Group (EWG) constructed a chain of evidence that linked genetic testing for Lynch syndrome in patients with newly diagnosed CRC with improved health outcomes in their relatives. We found that assessing patients who have newly diagnosed CRC with a series of genetic tests could lead to the identification of Lynch syndrome. Relatives of patients with Lynch syndrome could then be offered genetic testing, and, where indicated, colorectal, and possibly endometrial, cancer surveillance, with the expectation of improved health outcome. The EWG concluded that there is moderate certainly that such a testing strategy would provide moderate population benefit. Analytic Validity: The EWG found adequate evidence to conclude that the analytic sensitivity and specificity for preliminary and diagnostic tests were high. Clinical Validity: After accounting for the specific technologies and numbers of markers used, the EWG found at least adequate evidence to describe the clinical sensitivity and specificity for three preliminary tests, and for four selected testing strategies. These measures of clinical validity varied with each test and each strategy (see Clinical Considerations section). Clinical Utility: The EWG found adequate evidence for testing uptake rates, adherence to recommended surveillance activities, number of relatives approachable, harms associated with additional follow-up, and effectiveness of routine colonoscopy. This chain of evidence supported the use of genetic testing strategies to reduce morbidity/mortality in relatives with Lynch syndrome. Several genetic testing strategies were potentially effective, but none was clearly superior. The evidence for or against effectiveness of identifying mismatch repair (MMR) gene mutations in reducing endometrial cancer morbidity or mortality was inadequate. Contextual Issues: CRC is a common disease responsible for an estimated 52,000 deaths in the United States in 2007. In about 3% of newly diagnosed CRC, the underlying cause is a mutation in a MMR gene (Lynch syndrome) that can be reliably identified with existing laboratory tests. Relatives inheriting the mutation have a high (about 45% by age 70) risk of developing CRC. Evidence suggests these relatives will often accept testing and increased surveillance.