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Obesity is associated with shorter telomere length in prostate stromal cells in men with aggressive prostate cancer
Cancer Prevention Research ( IF 3.3 ) Pub Date : 2020-12-22 , DOI: 10.1158/1940-6207.capr-20-0250
Corinne E Joshu 1, 2, 3 , Christopher M Heaphy 4 , John R Barber 1 , Jiayun Lu 1 , Reza Zarinshenas 5 , Christine Davis 5 , Misop Han 6 , Tamara L Lotan 3, 5, 6 , Karen S Sfanos 3, 5, 6 , Angelo M De Marzo 2, 3, 5, 6 , Alan K Meeker 2, 3, 5, 6 , Elizabeth A Platz 1, 3, 5, 6
Affiliation  

In our prior studies, obesity was associated with shorter telomeres in prostate cancer associated stromal cells (CAS), and shorter CAS telomeres were associated with an increased risk of prostate cancer death. To determine if the association between obesity and shorter CAS telomeres is replicable, we conducted a pooled analysis of 790 men who were surgically treated for prostate cancer, whose tissue samples were arrayed on five tissue microarray (TMA) sets. Telomere signal was measured using a quantitative telomere-specific FISH assay and normalized to DAPI for 351 CAS cells (mean) per man; men were assigned their median value. Weight and height at surgery, collected via questionnaire or medical record, were used to calculate body mass index (BMI; kg/m2) and categorize men as normal (<25), overweight (25<=BMI<30), or obese (>=30). Analyses were stratified by grade and stage. Men were divided into tertiles of TMA- (overall) or TMA- and disease aggressiveness- (stratified) specific distributions; short CAS telomere status was defined by the bottom two tertiles. We used generalized linear mixed models to estimate the association between obesity and short CAS telomeres, adjusting for age, race, TMA set, pathologic stage and grade. Obesity was not associated with short CAS telomeres overall, or among men with non-aggressive disease. Among men with aggressive disease (Gleason>=4+3 and stage>T2), obese men had a 3-fold increased odds of short CAS telomeres (OR: 3.06, 95%CI: 1.07-8.75; P-trend=0.045) when compared to normal weight men. Telomere shortening in prostate stromal cells may be one mechanism through which lifestyle influences lethal prostate carcinogenesis.

中文翻译:

肥胖与侵袭性前列腺癌男性前列腺基质细胞端粒长度缩短有关

在我们之前的研究中,肥胖与前列腺癌相关基质细胞 (CAS) 中较短的端粒相关,而较短的 CAS 端粒与前列腺癌死亡风险增加有关。为了确定肥胖和较短的 CAS 端粒之间的关联是否可复制,我们对 790 名接受前列腺癌手术治疗的男性进行了汇总分析,他们的组织样本排列在五个组织微阵列 (TMA) 组上。使用定量端粒特异性 FISH 测定法测量端粒信号,并将每人 351 个 CAS 细胞(平均值)标准化为 DAPI;男性被分配了他们的中值。通过问卷或医疗记录收集的手术体重和身高用于计算体重指数(BMI;kg/m2)并将男性分为正常(<25)、超重(25<=BMI<30)或肥胖( >=30)。分析按等级和阶段进行分层。男性被分为 TMA-(整体)或 TMA- 和疾病侵袭性-(分层)特定分布的三分位数;短 CAS 端粒状态由底部的两个三分位数定义。我们使用广义线性混合模型来估计肥胖与短 CAS 端粒之间的关联,并调整年龄、种族、TMA 组、病理阶段和等级。总体而言,肥胖与 CAS 端粒短或患有非侵袭性疾病的男性无关。在患有侵袭性疾病(Gleason>=4+3 和阶段>T2)的男性中,肥胖男性的 CAS 端粒较短的几率增加了 3 倍(OR:3.06,95%CI:1.07-8.75;P 趋势=0.045)与正常体重的男性相比。前列腺基质细胞中的端粒缩短可能是生活方式影响致命前列腺癌发生的一种机制。
更新日期:2020-12-22
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