Circulating Prostate-Specific Antigen and Telomere Length in a Nationally Representative Sample of Men Without History of Prostate Cancer

Wahyu Wulaningsih; Yuliana Astuti; Tetsuya Matsuguchi; Putri Anggrandariyanny; Johnathan Watkins; PILAR Research Network

doi:10.1002/pros.23245

Circulating Prostate-Specific Antigen and Telomere Length in a Nationally Representative Sample of Men Without History of Prostate Cancer

Prostate. 2017 Jan;77(1):22-32. doi: 10.1002/pros.23245. Epub 2016 Aug 27.

Authors

Wahyu Wulaningsih^{1

2

3}, Yuliana Astuti^{4

5}, Tetsuya Matsuguchi⁶, Putri Anggrandariyanny², Johnathan Watkins^{3

7}; PILAR Research Network

Affiliations

¹ MRC Unit for Lifelong Health and Ageing, University College London, London, United Kingdom.
² Division of Haematology/Oncology, Faculty of Medicine, Gadjah Mada University, Yogyakarta, Indonesia.
³ PILAR Research and Education, Cambridge, United Kingdom.
⁴ Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
⁵ Department of Obstetrics/Gynaecology, Faculty of Medicine, Gadjah Mada University, Yogyakarta, Indonesia.
⁶ Department of Biochemistry and Biophysics, University of California, Driver Group, L.L.C., San Francisco, California.
⁷ Institute for Mathematical and Molecular Biomedicine, King's College London, London, United Kingdom.

PMID: 27566127
DOI: 10.1002/pros.23245

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 U.S. National Health and Nutrition Examination Survey (NHANES). A subsample of 1,127 men aged 40-85 years without 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 sensitivity analysis was performed by excluding men dying from prostate cancer during follow-up through to December 31, 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 (P_trend = 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).

Conclusion: Total PSA levels were strongly associated to LTL, particularly among non-Hispanic blacks. Our findings support a potential link between PSA and specific mechanisms contributing to prostate cancer development. Prostate 77:22-32, 2017. © 2016 Wiley Periodicals, Inc.

Keywords: prostate cancer; prostate-specific antigen; telomere; telomere length.

MeSH terms

Adult
Aged
Aged, 80 and over
Biomarkers, Tumor / blood*
Follow-Up Studies
Humans
Male
Middle Aged
Nutrition Surveys / methods
Prostate-Specific Antigen / blood*
Prostatic Neoplasms / blood*
Prostatic Neoplasms / epidemiology
Telomere / metabolism*
Telomere Homeostasis / physiology*

Substances

Biomarkers, Tumor
Prostate-Specific Antigen