Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Cancer Prev Res (Phila). 2021 Apr;14(4):463-470. doi: 10.1158/1940-6207.CAPR-20-0250. Epub 2020 Dec 22.
In our prior studies, obesity was associated with shorter telomeres in prostate cancer-associated stromal (CAS) cells, and shorter CAS telomeres were associated with an increased risk of prostate cancer death. To determine whether 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 4',6-diamidino-2-phenylindole 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/m) 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 nonaggressive 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% confidence interval: 1.07-8.75; = 0.045) when compared with normal weight men. Telomere shortening in prostate stromal cells may be one mechanism through which lifestyle influences lethal prostate carcinogenesis. PREVENTION RELEVANCE: This study investigates a potential mechanism underlying the association between obesity and prostate cancer death. Among men with aggressive prostate cancer, obesity was associated with shorter telomeres prostate cancer associated stromal cells, and shorter CAS telomeres have been associated with an increased risk of prostate cancer death.
在我们之前的研究中，肥胖与前列腺癌相关基质（CAS）细胞的端粒较短有关，而较短的 CAS 端粒与前列腺癌死亡风险增加有关。为了确定肥胖与较短的 CAS 端粒之间的关联是否具有可重复性，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，这些男性的组织样本被排列在五个组织微阵列（TMA）集中。使用定量端粒特异性 FISH 检测测量端粒信号，并将其归一化为每个男性 351 个 CAS 细胞（平均值）的 4'，6-二脒基-2-苯基吲哚；男性被分配他们的中位数。通过问卷或病历收集的手术时的体重和身高用于计算体重指数（BMI；kg/m），并将男性分为正常（<25）、超重（25 ≤ BMI < 30）或肥胖（≥30）。分析按等级和阶段分层。男性被分为 TMA-（总体）或 TMA-和疾病侵袭性-（分层）特定分布的三分位组；短 CAS 端粒状态由底部两个三分位组定义。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，调整年龄、种族、TMA 集、病理阶段和等级。肥胖与短 CAS 端粒之间没有总体关联，也与非侵袭性疾病的男性无关。在侵袭性疾病（Gleason≥4+3 和阶段>T2）的男性中，与正常体重男性相比，肥胖男性短 CAS 端粒的几率增加了 3 倍（OR：3.06；95%置信区间：1.07-8.75；p=0.045）。前列腺基质细胞中端粒缩短可能是生活方式影响致命性前列腺癌发生的一种机制。预防相关性：本研究调查了肥胖与前列腺癌死亡之间关联的潜在机制。在侵袭性前列腺癌男性中，肥胖与前列腺癌相关基质细胞的端粒较短有关，而较短的 CAS 端粒与前列腺癌死亡风险增加有关。
