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Cancer Prev Res (Phila). 2015 Aug;8(8):737-42. doi: 10.1158/1940-6207.CAPR-15-0097. Epub 2015 May 19.

Prediagnostic Obesity and Physical Inactivity Are Associated with Shorter Telomere Length in Prostate Stromal Cells.

Author information

1
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. cjoshu1@jhu.edu.
2
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
3
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
4
Department of Urology, University of California San Francisco, San Francisco, CA.
5
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
6
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
7
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts.
8
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
9
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
10
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.

Abstract

Obesity and inactivity have been associated with advanced-stage prostate cancer, and poor prostate cancer outcomes, though the underlying mechanism(s) is unknown. To determine whether telomere shortening, which has been associated with lethal prostate cancer, may be a potential underlying mechanism, we prospectively evaluated the association between measures of adiposity, physical activity, and telomere length in 596 participants in the Health Professionals Follow-up Study, who were surgically treated for prostate cancer. Using tissue microarrays, we measured telomere length in cancer and benign cells using a telomere-specific FISH assay. Adiposity and activity were assessed via questionnaire within 2 years of diagnosis. Adjusting for age, pathologic stage, and grade, the median and SD of the per cell telomere signals were determined for each man for stromal cells and cancer cells by adiposity and activity categories. Overweight/obese men (54%) were similar to normal weight men on most factors, but had higher Gleason sum and lower activity levels. Overweight/obese men had 7.4% shorter telomeres in stromal cells than normal weight men (P = 0.06). The least active men had shorter telomeres in stromal cells than more active men (Ptrend = 0.002). Men who were overweight/obese and the least active had the shortest telomeres in stromal cells (20.7% shorter; P = 0.0005) compared with normal weight men who were the most active. Cancer cell telomere length and telomere length variability did not differ by measures of adiposity or activity. Telomere shortening in prostate cells may be one mechanism through which lifestyle influences prostate cancer risk and outcomes.

PMID:
25990087
PMCID:
PMC4526348
DOI:
10.1158/1940-6207.CAPR-15-0097
[Indexed for MEDLINE]
Free PMC Article

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