Impact of gene-specific germline pathogenic variants on presentation of endometrial cancer in Lynch syndrome
Impact of gene-specific germline pathogenic variants on presentation of endometrial cancer in Lynch syndrome
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DOI：
10.1136/ijgc-2019-000277
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发表时间：
2019-05-01
影响因子：
4.8
通讯作者：
Raspagliesi, Francesco
中科院分区：
文献类型：
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作者：
Bogani, Giorgio;Ricci, Maria Teresa;Raspagliesi, Francesco
目的Lynch综合征是子宫内膜癌的危险因素。我们的目的是评估基因特异性生殖系致病性变异对子宫内膜癌患者的临床特征的影响。方法对诊断为子宫内膜癌和错配修复基因中生殖系致病性变异的患者进行回顾。根据ESGO-ESGO-ESTRO（欧洲肿瘤内科学会/欧洲妇科肿瘤学会/欧洲放射治疗和肿瘤学会）指南，根据风险类别对患者进行分类。分别对三组连续参数变量和非参数变量进行单因素方差分析和Kruskal-Wallis检验。结果共纳入子宫内膜癌合并Lynch综合征患者68例。10例（14.7%）患者因缺乏Lynch综合征相关基因的信息而被排除，因此留下58例（85.3%）患者可用于最终分析。在19例（32.7%）、33例（56.9%）和6例（10.3%）患者中分别观察到MLH 1、MSH 2和MSH 6致病性变体。诊断子宫内膜癌时的平均+/- SD年龄分别为51 ± 6.4、43.5 ± 7.4和60.3 ± 8.8岁（p=0.0002）。MLH 1、MSH 2和MSH 6组的非子宫内膜样癌患病率分别为15.7%、24.2%和0%（p=0.345）。根据ESMO-ESGO-ESTRO分类，低、中、高危子宫内膜癌分别占MLH 1组的47.3%、10.5%、42.1%，MSH 2组的57.6%、3%、39.4%，50%、结论MLH 1和MSH 2基因型患者发生子宫内膜癌的风险高于MSH 6基因型患者。
Objective Lynch syndrome is a risk factor for developing endometrial carcinoma. Our aim was to evaluate the impact of gene-specific germline pathogenic variants on clinical features of patients affected by endometrial cancer.Methods Patients with a diagnosis of endometrial cancer and with a germline pathogenic variant in mismatch repair genes were reviewed. Patients were classified on the basis of classes of risk according to the ESGO-ESGO-ESTRO (European Society of Medical Oncology/European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology) guidelines. One-way analysis of variance (ANOVA) and Kruskal-Wallis test were performed to compare three groups of continuous parametric and non-parametric variables, respectively. chi(2) test was used to analyze proportions.Results Overall, 68 patients with endometrial cancer and Lynch syndrome were evaluated. Ten (14.7%) patients were excluded because of absence of information about the gene involved in Lynch syndrome, thus leaving 58 (85.3%) patients available for the final analysis. MLH1, MSH2, and MSH6 pathogenic variants were observed in 19 (32.7%), 33 (56.9%), and six (10.3%) patients, respectively. Mean +/- SD age at endometrial cancer diagnosis was 51 +/- 6.4, 43.5 +/- 7.4, and 60.3 +/- 8.8 years (p=0.0002). Prevalence of non-endometrioid endometrial cancer was 15.7%, 24.2%, and 0% in the MLH1, MSH2, and MSH6 groups, respectively (p=0.345). According to the ESMO-ESGO-ESTRO classification, low, intermediate, and high risk endometrial cancer accounted for 47.3%, 10.5%, and 42.1% of the MLH1 group, 57.6%, 3%, and 39.4% of the MSH2 group, and 50%, 50% m and 0% of the MSH6 group (p=0.009).Conclusions Patients with MLH1 and MSH2 pathogenic variants are at a higher risk of early onset of endometrial cancer than patients with MSH6 pathogenic variants.