Abstract PR06: Prediagnostic obesity and inactivity are associated with shorter telomere length in prostate cancer-associated stromal cells

Abstract

Abstract Background: Meta-analyses and some cohort studies support that obese men are more likely to develop high-grade and advanced stage prostate cancer, recur after treatment, and die of this cancer. Physical activity, independent of body mass index, has been inversely associated with the development of advanced prostate cancer in some prospective studies. Mechanisms underlying these observations remain unknown. Previously, we showed that shorter telomere length in prostate-cancer associated stromal cells, especially in combination with greater variability in telomere length in cancer cells, was associated with a significantly increased risk of prostate cancer death after prostatectomy. Given this finding and because telomeres shorten with each round of replication, we hypothesized that obesity-associated growth factors influence telomere length, and might explain the more aggressive prostate cancer phenotype in obese men. Methods: We conducted a cross-sectional study of 596 men surgically treated for prostate cancer who participated in the Health Professionals Follow-up Study. Tissue microarrays containing areas of adenocarcinoma and benign tissue were stained using a telomere-specific FISH probe and using DAPI for total nuclear DNA. Image analysis was used to quantify telomeric signals in individual cancer and benign cells. Body mass index (BMI) and total physical activity were collected via questionnaire 2-years before the diagnosis. BMI was categorized into normal (≥25 kg/m2) and overweight/obese (>25 kg/m2). Total physical activity was categorized into tertiles. Adjusting for pathologic stage, grade and other factors, median and standard deviation of the telomere signal normalized to DAPI were determined for each man for cancer cells and cancer-associated stromal cells by categories of BMI and physical activity. Results: Overweight/obese men (54%) were similar to normal weight men on demographics and pathologic stage, but had higher Gleason sum and were less active than normal weight men. Overweight/obese men had shorter mean telomere length in cancer-associated stromal cells (7.5% shorter) than normal weight men (p=0.055). The least active men also had shorter mean telomere length in cancer-associated stromal cells than more active men (p-trend=0.004). Men who were overweight/obese and the least active had the shortest mean telomere length in cancer-associated stromal cells (20.7% shorter) compared to normal weight men who were the most active, who had the longest mean telomere length (p=0.0005). Cancer cell telomere length variability did not differ by BMI or activity level. Conclusions: Increased weight and decreased activity were associated with shorter mean telomere length in cancer-associated stromal cells. Telomere shortening in prostate cells may be one mechanism through which lifestyle influences prostate cancer risk and outcomes. Funding: Prostate Cancer Foundation, DOD, NIH/NCI, Seraph Foundation This abstract is also presented as Poster B43. Citation Format: Corinne E. Joshu, Sarah B. Peskoe, Christopher M. Heaphy, Stacey A. Kenfield, Lorelei A. Mucci, Edward Giovanucci, Meir J. Stampfer, Ghil Suk Yoon, Thomas Lee, Jessica L. Hicks, Angelo M. De Marzo, Alan K. Meeker, Elizabeth A. Platz. Prediagnostic obesity and inactivity are associated with shorter telomere length in prostate cancer-associated stromal cells. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr PR06.