Calculation of risk of colorectal and endometrial cancer among patients with Lynch syndrome.
Calculation of risk of colorectal and endometrial cancer among patients with Lynch syndrome.
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DOI：
10.1053/j.gastro.2009.07.039
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发表时间：
2009-11
期刊：
影响因子：
29.4
通讯作者：
Gruber SB
中科院分区：
文献类型：
--
作者：
Stoffel E;Mukherjee B;Raymond VM;Tayob N;Kastrinos F;Sparr J;Wang F;Bandipalliam P;Syngal S;Gruber SB
林奇综合征是最常见的遗传性结直肠癌(CRC)综合征。先前对结直肠癌和子宫内膜癌(EC)的终生风险的估计没有对确证进行控制，并且容易倾向于高估风险。我们研究了147个有错配修复(MMR)基因突变的家庭(55个MLH1，81个MSH2和11个MSH6)，这些突变在美国两个癌症遗传学诊所被发现。使用改进的隔离分析计算结直肠癌和结直肠癌的年龄特定累积风险(外显性)和危险比(HR)估计值，并与普通人群进行比较。每个家系的可能性取决于受结直肠癌影响的先证者和一级亲属，以减少确证偏差和高估外显性。我们分析了628例结直肠癌，男性和女性的平均年龄分别为42岁和47岁。男性结直肠癌累积危险度为66.08%(95%可信区间为59.47%~76.17%)，女性为42.71%(95%可信区间为36.57%~52.83%)，总的相对危险度分别为148.4和51.1。MLH1基因突变的男性患结直肠癌的风险最高。食管癌155例，确诊年龄中位数为47.5岁。食管癌的累积危险度为39.39%(95%CI为30.78%~46.94%)，总体HR为39.0%(95%CI为30.4%~50.2%)。女性发生结直肠癌或食管癌的累积风险为73.42%(95%可信区间为63.76%~80.54%)。即使在调整确定因素后，MMR基因突变携带者的结直肠癌和食管癌的终生风险也很高。这些估计对患者和提供者来说是有价值的；专门的癌症监测是必要的。
Lynch Syndrome is the most common hereditary colorectal cancer (CRC) syndrome. Previous estimates of lifetime risk for CRC and endometrial cancer (EC) did not control for ascertainment and were susceptible to bias towards overestimated risk. We studied 147 families with mismatch repair (MMR) gene mutations (55 MLH1, 81 MSH2, and 11 MSH6) identified at 2 U.S. cancer genetics clinics. Age-specific cumulative risks (penetrance) and hazard ratio (HR) estimates of CRC and EC risks were calculated and compared to the general population using modified segregation analysis. The likelihood for each pedigree was conditioned on the proband and first-degree relatives affected with CRC to reduce ascertainment bias and overestimation of penetrance. We analyzed 628 cases of CRC, diagnosed at median ages of 42 and 47 years for men and women, respectively. Cumulative risk of CRC was 66.08% (95% confidence interval [CI 59.47%–76.17%) for men and 42.71% (95% CI 36.57%–52.83%) for women, with overall HRs of 148.4 and 51.1, respectively. CRC risk was highest for males with mutations in MLH1. There were 155 cases of EC, diagnosed at median age of 47.5 years. Cumulative risk of EC was 39.39% (95% CI 30.78%–46.94%) with overall HR of 39.0% (95% CI 30.4%–50.2%). For women, the cumulative risk of CRC or EC was 73.42% (95% CI 63.76%–80.54%). Lifetime risks of CRC and EC in MMR gene mutation carriers are high even after adjusting for ascertainment. These estimates are valuable for patients and providers; specialized cancer surveillance is necessary.
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