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Expression and Genetic Variation in Neuroendocrine Signaling Pathways in Lethal and Nonlethal Prostate Cancer among Men Diagnosed with Localized Disease
Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.ORCID iD: 0000-0001-5533-7899
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts..
Örebro University Hospital. Örebro University, School of Medical Sciences. Department of Urology.
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2017 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 26, no 12, 1781-1787 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Recent data suggest that neuroendocrine signaling pathways may play a role in the progression of prostate cancer, particularly for early-stage disease. We aimed to explore whether expression of selected genes in the adrenergic, serotoninergic, glucocorticoid, and dopaminergic pathways differs in prostate tumor tissue from men with lethal disease compared to men with nonlethal disease.

METHODS: Based on the Swedish Watchful Waiting Cohort, we included 511 men diagnosed with incidental prostate cancer through TURP during 1977-1998 with follow-up up to 30 years. For those with tumor tissue (N=262), we measured mRNA expression of 223 selected genes included in neuroendocrine pathways. Using DNA from normal prostate tissue (N=396), we genotyped 36 SNPs from 14 receptor genes. Lethal prostate cancer was the primary outcome in analyses with pathway gene expression and genetic variants.

RESULTS: Differential expression of genes in the serotoninergic pathway was associated with risk of lethal prostate cancer (P=0.007); similar but weaker associations were noted for the adrenergic (P=0.014) and glucocorticoid (P=0.020) pathways. Variants of the HTR2A (rs2296972; P=0.002) and NR3CI (rs33388; P=0.035) genes (within the serotoninergic and glucocorticoid pathways) were associated with lethal cancer in over-dominant models. These genetic variants were correlated with expression of several genes in corresponding pathways (P<0.05).

CONCLUSIONS: Our findings lend support to hypothesis that the neuroendocrine pathways, particularly serotoninergic pathway, are associated with lethal outcome in the natural course of localized prostate cancer.

IMPACT: The current study provides evidence of the role of neuroendocrine pathways in prostate cancer progression which may have clinical utility.

Place, publisher, year, edition, pages
American Association for Cancer Research , 2017. Vol. 26, no 12, 1781-1787 p.
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:oru:diva-62461DOI: 10.1158/1055-9965.EPI-17-0453ISI: 000416858600012PubMedID: 28939587Scopus ID: 2-s2.0-85036617593OAI: oai:DiVA.org:oru-62461DiVA: diva2:1162386
Funder
Swedish Cancer Society, CAN 2013/650 CAN 2014/417
Note

Funding Agencies:

Karolinska Institutet and Robert Lundberg's Foundation  2016lund47503 

Karolinska Institutet 

Örebro University

Available from: 2017-12-04 Created: 2017-12-04 Last updated: 2017-12-19Bibliographically approved

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Carlsson, JessicaDavidsson, SabinaAndersson, Swen-OlofAndrén, OveFall, Katja

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