Joshu Corinne E, Peskoe Sarah B, Heaphy Christopher M, Kenfield Stacey A, Mucci Lorelei A, Giovannucci Edward L, Stampfer Meir J, Yoon Ghilsuk, Lee Thomas K, Hicks Jessica L, De Marzo Angelo M, Meeker Alan K, Platz Elizabeth A
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Prostate. 2018 Feb;78(3):233-238. doi: 10.1002/pros.23462. Epub 2017 Nov 22.
Current and recent smoking have been associated with a greater risk of prostate cancer recurrence and mortality, though the underlying mechanism is unknown.
To determine if telomere shortening, which has been associated with poor outcomes, may be a potential underlying mechanism, we prospectively evaluated the association between smoking status and telomere length in 567 participants in the Health Professionals Follow-up Study, who were surgically treated for prostate cancer. Using tissue microarrays (TMA), we measured telomere length in cancer and benign tissue, specifically stromal cells in the same TMA spot using a telomere-specific fluorescence in situ hybridization assay. Smoking status was collected via questionnaire 2-years before diagnosis. Adjusting for age, pathologic stage and grade, the median and standard deviation of the per-cell telomere signals were determined for each man for stromal cells and cancer cells by smoking categories. In sub-analyses, we restricted to men without major co-morbidities diagnosed before prostate cancer.
Overall, there were no associations between smoking status and telomere length or variability in stromal cells or cancer cells. However, among men without comorbidities, current smokers and former smokers who quit <10 years ago had the most variable telomere length in stromal cells (29.3% more variable than never smokers; P-trend = 0.0005) and in cancer cells (27.7% more variable than never smokers; P-trend = 0.05). Among men without comorbidities, mean telomere length did not differ by smoking status in stromal cells or cancer cells.
Telomere variability in prostate cells may be one mechanism through which smoking influences poor prostate cancer outcomes.
目前及近期吸烟与前列腺癌复发和死亡风险增加有关，但其潜在机制尚不清楚。
为了确定与不良预后相关的端粒缩短是否可能是一种潜在的潜在机制，我们前瞻性评估了健康专业人员随访研究中567名接受前列腺癌手术治疗的参与者的吸烟状况与端粒长度之间的关联。使用组织微阵列（TMA），我们通过端粒特异性荧光原位杂交测定法测量了癌组织和良性组织中的端粒长度，特别是同一TMA斑点中的基质细胞。吸烟状况通过诊断前2年的问卷收集。在调整年龄、病理分期和分级后，按吸烟类别确定每个男性基质细胞和癌细胞的每细胞端粒信号的中位数和标准差。在亚分析中，我们仅限于前列腺癌诊断前无重大合并症的男性。
总体而言，吸烟状况与基质细胞或癌细胞中的端粒长度或变异性之间没有关联。然而，在无合并症的男性中，目前吸烟者和戒烟<10年的既往吸烟者的基质细胞端粒长度变异性最大（比从不吸烟者高29.3%；P趋势=0.0005），癌细胞中的端粒长度变异性也最大（比从不吸烟者高27.7%；P趋势=0.05）。在无合并症的男性中，基质细胞或癌细胞中的平均端粒长度在吸烟状况方面没有差异。
前列腺细胞中的端粒变异性可能是吸烟影响前列腺癌不良预后的一种机制。
