54P Circulating prostate-specific antigen and telomere length in a nationally representative sample of men without history of prostate cancer

Abstract

Background We investigated the association of prostate-specific antigen (PSA) with leukocyte telomere length, which may be altered in preclinical prostate malignancies. Methods This study was based on the 2001-2002 USA National Health and Nutrition ExaminationSurvey(NHANES). Asubsampleof1,127 menaged40-85yearswithout prior history of prostate cancer who provided informed consent and blood samples were selected. Leukocyte telomere length (LTL) relative to standard DNA reference (T/S ratio) was quantified by polymerase chain reaction (PCR). Survey-weighted multivariable linear regression was performed to examine T/S ratio across quintiles of total and free PSA and free-to-total PSA ratio (%fPSA). A sensitivityanalysis was performed by excluding men dying from prostate cancer during follow-up through to 31 December 2006. Stratification analyses were carried out to assess any effect modification by age group, race, body mass index (BMI) and levels of C-reactive protein (CRP), a marker of inflammation. Results Higher total PSA levels were associated to longer LTL, with approximately 8% increase in log-transformed T/S ratio (95% confidence interval [CI]: 2-13%) among men in the highest quintile of total PSA compared to the lowest in the fully adjusted model (Ptrend —0.01). No significant association was found for free PSA or %fPSA, although nonlinearity between all PSA measures and T/S ratio was indicated. Similar results were found after excluding men who died from prostate cancer during follow-up. We also found the associations between total PSA and T/S ratio to be strongest among non-Hispanic blacks, non-obese men (BMI <30 kg/m2), and those with low CRP. However, a significant interaction was only found between total PSA and race/ethnicity (P interaction— 0.01). Conclusions Total PSA levels were strongly associated to leukocyte telomere length, particularly among non-Hispanic blacks. Our findings support a potential link between PSA and specific mechanisms contributing to prostate cancer development. Legal entity responsible for the study King's College London Funding PILAR Research and Education Foundation Disclosure All authors have declared no conflicts ofinterest.