Health Benefits and Cost-Effectiveness of Primary Genetic Screening for Lynch Syndrome in the General Population
Health Benefits and Cost-Effectiveness of Primary Genetic Screening for Lynch Syndrome in the General Population
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DOI：
10.1158/1940-6207.capr-10-0262
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发表时间：
2011-01-01
影响因子：
3.3
通讯作者：
Burt, Randall W.
中科院分区：
文献类型：
--
作者：
Dinh, Tuan A.;Rosner, Benjamin I.;Burt, Randall W.
在目前的临床实践中，检测Lynch综合征突变的基因检测理想地始于对受癌症影响的个体的诊断检测，然后向有风险的亲属提供预测检测。另一种值得探索的策略是通过人口统计学和家族史筛选未受影响的个体，并为携带突变的风险超过选定阈值的个体提供基因检测。这种方法是否会以相对于目前的护理标准具有成本效益的方式改善健康结果还有待证明。为此，我们开发了一个模拟框架，将结直肠癌和子宫内膜癌模型与5代家族史模型相结合，以预测20种主要筛查策略的健康和经济结果（在广泛的依从性水平下），旨在检测具有错配修复基因突变的个体及其高危亲属。这些策略的特点是（i）不同的筛查年龄开始风险评估和（ii）不同的风险阈值以上，以实施基因检测。对于每种策略，10万个模拟个体，代表美国。S.人群，从20岁开始随访，并将结果与当前实践进行比较。研究结果表明，从25岁、30岁或35岁开始进行风险评估，然后对突变风险超过5%的人进行基因检测，可使突变携带者的结直肠癌和子宫内膜癌发病率分别降低约12.4%和8.8%。对于包含392个突变携带者的100，000人的人群，该策略将质量调整生命年（QALY）增加了约135，平均成本效益比为26，000美元/QALY。错配修复基因突变筛查的成本效益与一般人群中接受的癌症筛查活动（如结直肠癌筛查、宫颈癌筛查和乳腺癌筛查）的成本效益相当。这些结果表明，对个体进行错配修复基因突变的初步筛查，从25岁至35岁之间的风险评估开始，然后对风险超过5%的人进行基因检测，是一种可以改善健康结果的策略。Cancer Prev Res; 4（1）：9-22. (C)2010年AACR。
In current clinical practice, genetic testing to detect Lynch syndrome mutations ideally begins with diagnostic testing of an individual affected with cancer before offering predictive testing to at-risk relatives. An alternative strategy that warrants exploration involves screening unaffected individuals via demographic and family histories, and offering genetic testing to those individuals whose risks for carrying a mutation exceed a selected threshold. Whether this approach would improve health outcomes in a manner that is cost-effective relative to current standards of care has yet to be demonstrated. To do so, we developed a simulation framework that integrated models of colorectal and endometrial cancers with a 5-generation family history model to predict health and economic outcomes of 20 primary screening strategies (at a wide range of compliance levels) aimed at detecting individuals with mismatch repair gene mutations and their at-risk relatives. These strategies were characterized by (i) different screening ages for starting risk assessment and (ii) different risk thresholds above which to implement genetic testing. For each strategy, 100,000 simulated individuals, representative of the U. S. population, were followed from the age of 20, and the outcomes were compared with current practice. Findings indicated that risk assessment starting at ages 25, 30, or 35, followed by genetic testing of those with mutation risks exceeding 5%, reduced colorectal and endometrial cancer incidence in mutation carriers by approximately 12.4% and 8.8%, respectively. For a population of 100,000 individuals containing 392 mutation carriers, this strategy increased quality-adjusted life-years (QALY) by approximately 135 with an average cost-effectiveness ratio of $26,000 per QALY. The cost-effectiveness of screening for mismatch repair gene mutations is comparable to that of accepted cancer screening activities in the general population such as colorectal cancer screening, cervical cancer screening, and breast cancer screening. These results suggest that primary screening of individuals for mismatch repair gene mutations, starting with risk assessment between the ages of 25 and 35, followed by genetic testing of those whose risk exceeds 5%, is a strategy that could improve health outcomes in a cost-effective manner relative to current practice. Cancer Prev Res; 4(1): 9-22. (C) 2010 AACR.