Risks of Less Common Cancers in Proven Mutation Carriers With Lynch Syndrome
Risks of Less Common Cancers in Proven Mutation Carriers With Lynch Syndrome
复制标题
DOI：
10.1200/jco.2012.43.2278
复制
发表时间：
2012-12-10
影响因子：
45.3
通讯作者：
Vasen, Hans F. A.
中科院分区：
文献类型：
--
作者：
Engel, Christoph;Loeffler, Markus;Vasen, Hans F. A.
目的林奇综合征患者患结肠癌和子宫内膜癌的风险较高，但患其他较少见癌症的风险也较高。这项回顾性队列研究的目的是在错配修复(MMR)基因MLH1、MSH2和MSH6的致病突变已证实的携带者中提供这些不太常见的癌症的风险估计。患者和方法数据来自德国和荷兰国家林奇综合征登记中心。分析了七种不同的癌症类型：胃癌、小肠癌、膀胱癌、其他尿路上皮癌、乳腺癌、卵巢癌和前列腺癌。使用Kaplan-Meier方法计算年龄、性别和MMR基因特异性累积风险(CRS)。通过计算标准化发病率比(SIRS)，将特定性别的发病率与总体人群发病率进行比较。结果2118例MMR基因突变携带者中，MLH1为806例，MSH2为1004例，MSH6为308例。所有癌症的发病率都明显高于普通人群。男性患小肠癌的风险最高(SIR，251；95%CI，177至346；CR70岁，12.0；95%CI，5.7至18.2)。乳腺癌的SIR为1.9(95%CI，1.4~2.4)，CR为14.4(95%CI，9.5~19.3)。MSH2突变携带者发生尿路上皮癌的风险明显高于MLH1或MSH6携带者。结论在Lynch综合征患者的癌症监测和预防方案中，应考虑不同性别和不同基因的癌症风险差异。J Clin Oncol30：4409-4415。(C)2012年美国临床肿瘤学会
PurposePatients with Lynch syndrome are at high risk for colon and endometrial cancer, but also at an elevated risk for other less common cancers. The purpose of this retrospective cohort study was to provide risk estimates for these less common cancers in proven carriers of pathogenic mutations in the mismatch repair (MMR) genes MLH1, MSH2, and MSH6.Patients and MethodsData were pooled from the German and Dutch national Lynch syndrome registries. Seven different cancer types were analyzed: stomach, small bowel, urinary bladder, other urothelial, breast, ovarian, and prostate cancer. Age-, sex-and MMR gene-specific cumulative risks (CRs) were calculated using the Kaplan-Meier method. Sex-specific incidence rates were compared with general population incidence rates by calculating standardized incidence ratios (SIRs). Multivariate Cox regression analysis was used to estimate the impact of sex and mutated gene on cancer risk.ResultsThe cohort comprised 2,118 MMR gene mutation carriers (MLH1, n = 806; MSH2, n = 1,004; MSH6, n = 308). All cancers were significantly more frequent than in the general population. The highest risks were found for male small bowel cancer (SIR, 251; 95% CI, 177 to 346; CR at 70 years, 12.0; 95% CI, 5.7 to 18.2). Breast cancer showed an SIR of 1.9 (95% CI, 1.4 to 2.4) and a CR of 14.4 (95% CI, 9.5 to 19.3). MSH2 mutation carriers had a considerably higher risk of developing urothelial cancer than MLH1 or MSH6 carriers.ConclusionThe sex-and gene-specific differences of less common cancer risks should be taken into account in cancer surveillance and prevention programs for patients with Lynch syndrome. J Clin Oncol 30: 4409-4415. (C) 2012 by American Society of Clinical Oncology