Gene-Specific Variation in Colorectal Cancer Surveillance Strategies for Lynch Syndrome.
Gene-Specific Variation in Colorectal Cancer Surveillance Strategies for Lynch Syndrome.
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DOI：
10.1053/j.gastro.2021.04.010
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发表时间：
2021-08
期刊：
影响因子：
29.4
通讯作者：
中科院分区：
文献类型：
--
作者：
林奇综合征与4个错配修复(MMR)基因的致病变异有关，这些基因增加了结直肠癌(CRC)的终生风险。指南建议，对于所有Lynch综合征相关变异携带者，无论基因产物如何，从25年开始，每1-2年进行一次结肠镜检查，进行密集的CRC监测。我们构建了一个模拟模型来分析不同的结肠镜检查开始年龄和每个MMR基因的监测间隔(MLH1、MSH2、MSH6和PMS2)对结直肠癌发病率和死亡率、质量调整生命年(QALY)和成本的影响。根据已发表的文献，我们为每种MMR变异的患者开发了林奇综合征进展的马尔可夫模拟模型。该模型模拟了林奇综合征携带者的临床试验，不同的结肠镜检查开始年龄(从25-40岁递增5年)和监测间隔(1-5年)。我们评估了每个基因的最优策略，即具有最高QALY和增量成本效益比低于100,000美元支付意愿阈值(WTP)的策略。对MLH1和MSH2基因致病变异患者的最佳监测是从25岁开始的结肠镜检查，监测间隔1-2年。分别在35岁和40岁开始结肠镜检查，间隔3年，对于带有MSH6或PMS2致病变异的患者来说，成本效益高。我们开发了一个模拟模型，根据MMR变异为Lynch综合征患者选择最佳监测开始年龄和间隔。该模型支持对MLH1或MSH2中与林奇综合征相关变异的患者进行密集监测的建议。然而，对于患有MSH6或PMS2的林奇综合征相关变异的患者，可以考虑分别在35年和40年以及每隔3年开始监测。
Lynch syndrome is associated with pathogenic variants in 4 mismatch repair (MMR) genes that increase lifetime risk of colorectal cancer (CRC). Guidelines recommend intensive CRC surveillance with colonoscopy every 1–2 years starting at 25 years for all carriers of Lynch syndrome-associated variants, regardless of gene product. We constructed a simulation model to analyze the effects of different ages of colonoscopy initiation and surveillance intervals for each MMR gene (MLH1, MSH2, MSH6, and PMS2) on CRC incidence and mortality, quality-adjusted life-years (QALYs), and cost. Using published literature, we developed a Markov simulation model of Lynch syndrome progression for patients with each MMR variant. The model simulated clinical trials of Lynch syndrome carriers, varying age of colonoscopy initiation (5-year increments from 25–40 years) and surveillance intervals (1–5 years). We assessed the optimal strategy for each gene, defined as the strategy with the highest QALYs and incremental cost-effectiveness ratio below a $100,000 willingness-to-pay threshold (WTP). Optimal surveillance for patients with pathogenic variants in the MLH1 and MSH2 genes was colonoscopy starting at 25 years of age, with 1–2 year surveillance intervals. Initiating colonoscopy at age 35 and 40 years, with 3-year intervals, was cost effective for patients with pathogenic variants in MSH6 or PMS2, respectively. We developed a simulation model to select optimal surveillance starting ages and intervals for patients with Lynch syndrome based on MMR variant. The model supports recommendations for intensive surveillance of patients with Lynch syndrome-associated variants in MLH1 or MSH2. However, for patients with Lynch syndrome-associated variants of MSH6 or PMS2, later initiation of surveillance at 35 and 40 years, respectively, and at 3-year intervals, can be considered.
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影响因子：
24.5
作者：
Møller P;Seppälä TT;Bernstein I;Holinski-Feder E;Sala P;Gareth Evans D;Lindblom A;Macrae F;Blanco I;Sijmons RH;Jeffries J;Vasen HFA;Burn J;Nakken S;Hovig E;Rødland EA;Tharmaratnam K;de Vos Tot Nederveen Cappel WH;Hill J;Wijnen JT;Jenkins MA;Green K;Lalloo F;Sunde L;Mints M;Bertario L;Pineda M;Navarro M;Morak M;Renkonen-Sinisalo L;Valentin MD;Frayling IM;Plazzer JP;Pylvanainen K;Genuardi M;Mecklin JP;Moeslein G;Sampson JR;Capella G;Mallorca Group
通讯作者：
Mallorca Group
影响因子：
11.5
作者：
Malesci, Alberto;Laghi, Luigi;Santoro, Armando
通讯作者：
Santoro, Armando
影响因子：
8.8
作者：
Dominguez-Valentin, Mev;Sampson, Julian R.;Moller, Pal
通讯作者：
Moller, Pal
DOI：
10.6004/jnccn.2019.0044
发表时间：
2019-09-01
影响因子：
13.4
作者：
Gupta, Samir;Provenzale, Dawn;Ogba, Ndiya
通讯作者：
Ogba, Ndiya
影响因子：
29.4
作者：
Hampel, H;Stephens, JA;de la Chapelle, A
通讯作者：
de la Chapelle, A