University of Leipzig, Leipzig, Germany.
J Clin Oncol. 2012 Dec 10;30(35):4409-15. doi: 10.1200/JCO.2012.43.2278. Epub 2012 Oct 22.
Patients 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.
Data 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.
The 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.
The 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.
林奇综合征患者患结肠和子宫内膜癌的风险较高，但患其他罕见癌症的风险也有所增加。本回顾性队列研究的目的是为经证实携带错配修复（MMR）基因 MLH1、MSH2 和 MSH6 致病性突变的患者提供这些罕见癌症的风险估计。
数据来自德国和荷兰国家林奇综合征登记处。分析了七种不同的癌症类型：胃、小肠、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 法计算年龄、性别和 MMR 基因特异性累积风险（CR）。通过计算标准化发病比（SIR）比较特定性别发病率与一般人群发病率。使用多变量 Cox 回归分析估计性别和突变基因对癌症风险的影响。
该队列包括 2118 名 MMR 基因突变携带者（MLH1，n=806；MSH2，n=1004；MSH6，n=308）。所有癌症的发生率均明显高于一般人群。男性小肠癌的风险最高（SIR，251；95%CI，177 至 346；70 岁时的 CR，12.0；95%CI，5.7 至 18.2）。乳腺癌的 SIR 为 1.9（95%CI，1.4 至 2.4），CR 为 14.4（95%CI，9.5 至 19.3）。与 MLH1 或 MSH6 携带者相比，MSH2 突变携带者发生尿路上皮癌的风险显著增加。
在林奇综合征患者的癌症监测和预防计划中，应考虑罕见癌症风险的性别和基因特异性差异。
