Abstract | Background: Experimental and epidemiologic evidence supports the role of circulating insulin-like growth factor-1 (IGF-1) levels with the risk of prostate cancer. Most circulating IGF-1 is bound to specific binding proteins, and only about 5% circulates in a free form. We explored the relation of free IGF-1 and other components of the IGF system with lethal prostate cancer. Methods: Using prospectively collected samples, we undertook a nested case-only analysis among 434 men with lethal prostate cancer and 524 men with indolent, nonlethal prostate cancer in the Physicians' Health Study and the Health Professionals Follow-up Study. Prediagnostic plasma samples were assayed for free IGF-1 and total IGF-1, acid labile subunit, pregnancy-associated plasma protein A ( PAPP-A), and intact and total IGF binding protein 4. We estimated odds ratios ( ORs) and corresponding 95% confidence intervals (CIs) for the associations between IGF-1-related biomarkers and lethal prostate cancer using unconditional logistic regression models adjusted for age, height, and body mass index. Results: Men in the highest quartile of PAPP-A levels had 42% higher odds of lethal prostate cancer (pooled adjusted OR = 1.42, 95% CI = 1.04 to 1.92) compared with men in the lowest 3 quartiles. There were no statistically significant differences in the other plasma analytes. The positive association between PAPP-A and lethal prostate cancer was present among men with intact PTEN but not among those with tumor PTEN loss (2-sided P interaction = .001). Conclusions: Our study provides suggestive evidence that among men who later develop prostate cancer, higher plasma PAPP-A levels measured prior to diagnosis are associated with increased risk of lethal compared with indolent disease.
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Authors | Chaoran Ma, Ye Wang, Kathryn M Wilson, Lorelei A Mucci, Meir J Stampfer, Michael Pollak, Kathryn L Penney |
Journal | JNCI cancer spectrum
(JNCI Cancer Spectr)
Vol. 6
Issue 1
(02 2022)
ISSN: 2515-5091 [Electronic] England |
PMID | 35047751
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Copyright | © The Author(s) 2021. Published by Oxford University Press. |
Chemical References |
- Biomarkers, Tumor
- IGF1 protein, human
- INSL4 protein, human
- Insulin-Like Growth Factor Binding Protein 3
- Intercellular Signaling Peptides and Proteins
- Insulin-Like Growth Factor I
- PTEN Phosphohydrolase
- PTEN protein, human
- Pregnancy-Associated Plasma Protein-A
- PAPPA protein, human
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Topics |
- Adult
- Age Factors
- Aged
- Aged, 80 and over
- Biomarkers, Tumor
(blood)
- Body Height
- Body Mass Index
- Case-Control Studies
- Confidence Intervals
- Enzyme-Linked Immunosorbent Assay
- Follow-Up Studies
- Humans
- Insulin-Like Growth Factor Binding Protein 3
(blood)
- Insulin-Like Growth Factor I
(analysis, metabolism)
- Intercellular Signaling Peptides and Proteins
(blood)
- Logistic Models
- Male
- Middle Aged
- Odds Ratio
- PTEN Phosphohydrolase
(blood)
- Pregnancy-Associated Plasma Protein-A
(analysis, metabolism)
- Prostatic Neoplasms
(blood, classification, mortality)
- Risk
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