title: Prediagnostic Obesity and Physical Inactivity Are Associated with Shorter Telomere Length in Prostate Stromal Cells.
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.
authors.affiliation: 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.
authors.forename: Corinne E
authors.initials: CE
authors.lastname: Joshu
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Peskoe
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Heaphy
authors.affiliation: Department of Urology, University of California San Francisco, San Francisco, CA.
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Kenfield
authors.affiliation: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Van Blarigan
authors.affiliation: 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.
authors.forename: Lorelei A
authors.initials: LA
authors.lastname: Mucci
authors.affiliation: 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.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Giovannucci
authors.affiliation: 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.
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: GhilSuk
authors.initials: G
authors.lastname: Yoon
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Lee
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Hicks
authors.affiliation: 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.
authors.forename: Angelo M
authors.initials: AM
authors.lastname: De Marzo
authors.affiliation: 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.
authors.forename: Alan K
authors.initials: AK
authors.lastname: Meeker
authors.affiliation: 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.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platz
mesh_terms: D000328:Adult; D000368:Aged; D005500:Follow-Up Studies; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009765:Obesity / Q000503:physiopathology*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D012307:Risk Factors; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D059505:Telomere Homeostasis / Q000235:genetics; D059506:Telomere Shortening / Q000235:genetics*; D046888:Tissue Array Analysis