Population Health Department, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, Australia.
School of Public Health, University of Queensland, Brisbane, Australia.
J Gynecol Oncol. 2018 May;29(3):e39. doi: 10.3802/jgo.2018.29.e39. Epub 2018 Feb 23.
The risk of developing endometrial cancer (EC) and/or survival following a diagnosis of EC might differ by tumor DNA mismatch repair (MMR) status. We assessed the association between tumor MMR status (classified as MMR-proficient, somatic MMR-deficient, germline MMR-deficient) and the risk of developing EC and survival following a diagnosis of EC.
We analyzed data from women who participated in the Australian National Endometrial Cancer Study (ANECS) conducted between 2005 and 2007. Risk analyses (698 cases/691 population controls) utilized sociodemographic and lifestyle information obtained from telephone interviews at recruitment. For survival analyses (728 cases), patients' clinical data was abstracted from medical records, and survival data were obtained via linkage with the Australian National Death Index. We used logistic regression analysis to evaluate the associations between tumor MMR status and EC risk, and proportional hazards models to perform survival analyses with adjustment of known prognostic factors.
Established risk factors for EC did not differ significantly by tumor MMR status. In analyses including all EC subtypes, overall and EC-specific survival did not differ by tumor MMR status. Among women with the most common endometrioid subtype, EC-specific survival was worse for women with somatic MMR-deficient EC compared to women with MMR-proficient EC (hazard ratio [HR]=2.18; 95% confidence interval [CI]=1.19-4.01).
The risk of EC is not associated with MMR status. Accurate separation of germline from somatic causes of MMR deficiency suggests that patients with endometrioid subtype somatic MMR-deficient tumors have poorer EC-specific survival than those with MMR-proficient tumors, after accounting for other prognostic factors.
肿瘤错配修复（MMR）状态不同，子宫内膜癌（EC）的发病风险和/或生存可能存在差异。本研究评估了肿瘤 MMR 状态（分为 MMR 功能正常、体细胞 MMR 缺陷、种系 MMR 缺陷）与 EC 发病风险和 EC 诊断后的生存之间的关系。
我们分析了参加 2005 年至 2007 年澳大利亚国家子宫内膜癌研究（ANECS）的女性的数据。风险分析（698 例病例/691 例人群对照）利用招募时电话访谈获得的社会人口统计学和生活方式信息。对于生存分析（728 例病例），从病历中提取患者的临床数据，并通过与澳大利亚国家死亡索引链接获得生存数据。我们使用逻辑回归分析评估肿瘤 MMR 状态与 EC 风险之间的关系，并使用比例风险模型调整已知的预后因素进行生存分析。
EC 的既定风险因素与肿瘤 MMR 状态无显著差异。在包括所有 EC 亚型的分析中，总体和 EC 特异性生存与肿瘤 MMR 状态无关。在最常见的子宫内膜样亚型女性中，与 MMR 功能正常的 EC 相比，体细胞 MMR 缺陷的 EC 患者的 EC 特异性生存更差（风险比[HR]=2.18；95%置信区间[CI]=1.19-4.01）。
EC 的发病风险与 MMR 状态无关。准确区分 MMR 缺陷的种系和体细胞原因表明，在考虑其他预后因素后，具有子宫内膜样亚型体细胞 MMR 缺陷肿瘤的患者比 MMR 功能正常的肿瘤患者的 EC 特异性生存更差。
