Department of Biostatistics and Epidemiology, Graduate School of Public Health, MSC-UPR, San Juan, Puerto Rico.
Int J Gynecol Cancer. 2012 Jun;22(5):826-9. doi: 10.1097/IGC.0b013e31825104de.
Lynch syndrome (LS) is an autosomal dominant disorder caused by DNA mismatch repair (MMR) system deficiencies. Women affected by LS present a 40% to 60% lifetime risk of endometrial cancer (EC).
This case-case study aims to determine the frequency of the hMLH1, hMSH2, and hMSH6 MMR proteins and the factors (age, family history of cancer [FHC] related to LS, and body mass index [BMI]) associated to their absence in EC patients attending the University District Hospital of San Juan, Puerto Rico.
Twenty cases were preliminary evaluated for the MMR protein expression by immunohistochemistry testing and classified as positive cases (presence of protein) or negative cases (absence of protein). The statistical analysis was based on the logistic regression model using the maximum likelihood estimation (MLE). The Bayesian approach was used to determine the posterior probability (posterior Pr[odds ratio {OR} > 1]).
Results showed absence for at least 1 MMR protein in 25% of the cases, 15% for hMLH1, and 10% for hMSH2. None of the cases showed an absence for hMSH6. The MLE demonstrated that women diagnosed with EC before the age of 50 (OR: 12.4; 95% confidence interval [CI] = 0.5-322.7), having FHC related to LS (OR: 17.7; 95% CI = 0.6-534.6), and having lower BMI (OR: 2.38; 95% CI = 0.39-14.28) present higher odds than their counterparts of lacking an MMR protein, once adjusted for potential predictors (P > 0.05). The posterior probability that an excess risk of lacking an MMR protein occurs was 95% or greater for each predictor.
Our study in this Hispanic population supports previous studies in that younger age, FHC, and lower BMI are associated with increased odds of having an absence of MMR protein expression. Further studies with larger sample sizes should be performed.
林奇综合征（LS）是一种常染色体显性遗传疾病，由 DNA 错配修复（MMR）系统缺陷引起。受 LS 影响的女性一生中罹患子宫内膜癌（EC）的风险为 40%至 60%。
本病例对照研究旨在确定波多黎各圣胡安大学区医院就诊的 EC 患者中 hMLH1、hMSH2 和 hMSH6 MMR 蛋白的缺失频率以及与这些蛋白缺失相关的因素（年龄、与 LS 相关的癌症家族史[FHC]和体重指数[BMI]）。
通过免疫组织化学检测对 20 例患者进行了 MMR 蛋白表达的初步评估，并将其分类为阳性病例（存在蛋白）或阴性病例（缺失蛋白）。统计分析基于最大似然估计（MLE）的逻辑回归模型。采用贝叶斯方法确定后验概率（后验 Pr[优势比{OR}＞1]）。
结果显示，25%的病例至少缺失 1 种 MMR 蛋白，15%的病例缺失 hMLH1，10%的病例缺失 hMSH2。没有病例缺失 hMSH6。MLE 表明，50 岁以下被诊断为 EC 的女性（OR：12.4；95%置信区间[CI]：0.5-322.7）、有 LS 相关 FHC（OR：17.7；95% CI：0.6-534.6）和 BMI 较低（OR：2.38；95% CI：0.39-14.28）的患者比他们对应的 MMR 蛋白缺失的患者更有可能出现较高的优势，在调整了潜在预测因素后（P＞0.05）。对于每个预测因素，缺乏 MMR 蛋白表达的风险增加的后验概率为 95%或更高。
在我们对西班牙裔人群的研究中，支持了之前的研究结果，即年龄较小、FHC 和较低的 BMI 与 MMR 蛋白表达缺失的几率增加相关。应该进行更多的、具有更大样本量的研究。
