Case-case study of factors associated to hMLH1, hMSH2, and hMSH6 protein expression among endometrial cancer patients of the University District Hospital of San Juan, Puerto Rico.
Case-case study of factors associated to hMLH1, hMSH2, and hMSH6 protein expression among endometrial cancer patients of the University District Hospital of San Juan, Puerto Rico.
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DOI：
10.1097/igc.0b013e31825104de
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发表时间：
2012-06
期刊：
影响因子：
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通讯作者：
Cruz-Correa MR
中科院分区：
文献类型：
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作者：
González L;Ortiz AP;Suárez EL;Umpierre S;Billoch J;Marcos MJ;Joy L;Charneco E;Lacourt MY;Bernabe-Dones RD;Cruz-Correa MR
Lynch综合征(LS)是由DNA错配修复系统缺陷引起的常染色体显性遗传性疾病。受LS影响的女性有40%至60%的终生风险为子宫内膜癌(EC)。这项病例-病例研究旨在确定在波多黎各圣胡安大学区医院就诊的EC患者中hMLH1、hMSH2和hMSH6 MMR蛋白的频率以及与它们缺失相关的因素(年龄、LS相关的癌症家族史[FHC]和体重指数[BMI])。免疫组织化学检测20例MMR蛋白的表达，分为阳性(有蛋白)和阴性(无蛋白)两组。统计分析基于Logistic回归模型，采用最大似然估计(MLE)。使用贝叶斯方法确定后验概率{后验Pr[OR>；1]}。结果显示，25%的病例中至少有一种MMR蛋白缺失；15%的病例hMLH1和10%的病例hMSH2缺失。没有一例病例显示hMSH6缺失。最大似然法分析显示，在调整潜在预测因素后，50岁前确诊为EC的女性(OR：12.4；95%CI=0.5-322.7)、有与LS相关的FHC(OR：17.7；95%CI=0.6-534.6)、体重指数较低(OR：2.38；95%CI=0.39-14.28)的女性比她们的同龄人有更高的MMR蛋白缺乏率(p>；0.05)。对于每个预测因子，发生缺乏Mmr蛋白的过量风险的后验概率为≥95%。我们在拉美裔人群中的研究支持了先前的研究，即年龄较小、FHC和较低的BMI与MMR蛋白表达缺失的几率增加有关。应进行更大样本量的进一步研究。
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[OR>1]}. Results showed absence for at least one 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%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 adjusting for potential predictors (p > .05). The posterior probability that an excess risk of lacking an MMR protein occurs was ≥ 95% 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.