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Sökning: onr:"swepub:oai:DiVA.org:oru-52692" > Cholesterol Metabol...

Cholesterol Metabolism and Prostate Cancer Lethality

Stopsack, Konrad H., (författare)
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Department of Internal Medicine, Mayo Clinic, Rochester, USA
Gerke, Travis A., (författare)
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Department of Epidemiology, College of Medicine and College of Public Health and Health Professions, University of Florida, Gainesville FL, USA
Sinnott, Jennifer A., (författare)
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Department of Statistics, Ohio State University, Columbus OH, USA
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Penney, Kathryn L., (författare)
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, USA; Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, Boston, USA
Tyekucheva, Svitlana, (författare)
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, USA; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, USA
Sesso, Howard D., (författare)
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Divisions of Preventive Medicine and Aging, Department of Medicine, Brigham and Women's Hospital, Boston, USA; Divisions of Preventive Medicine and Aging, Department of Medicine, Harvard Medical School, Boston, USA
Andersson, Swen-Olof, 1949- (författare)
Örebro universitet, Institutionen för hälsovetenskaper, Department of Urology, Örebro University Hospital, Örebro, Sweden
Andrén, Ove, 1963- (författare)
Örebro universitet, Institutionen för medicinska vetenskaper, Department of Urology, Örebro University Hospital, Örebro, Sweden
Cerhan, James R., (författare)
Department of Health Sciences Research, Mayo Clinic, Rochester, USA
Giovannucci, Edward L., (författare)
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, USA; Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, Boston, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, USA
Mucci, Lorelei A., (författare)
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston MA, USA; Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, Boston MA, USA
Rider, Jennifer R., (författare)
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Department of Epidemiology, Boston University School of Public Health, Boston, USA
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Örebro universitet Institutionen för hälsovetenskaper. (creator_code:org_t)
Örebro universitet Institutionen för medicinska vetenskaper. (creator_code:org_t)
2016
Engelska.
Ingår i: Cancer Research. - American Association for Cancer Research Inc.. - 0008-5472. ; 76:16, s. 4785-4790
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Cholesterol metabolism has been implicated in prostate cancer pathogenesis. Here, we assessed the association of intratumoral mRNA expression of cholesterol synthesis enzymes, transporters, and regulators in tumor specimen at diagnosis and lethal prostate cancer, defined as mortality or metastases from prostate cancer in contrast to nonlethal disease without evidence of metastases after at least 8 years of follow-up. We analyzed the prospective prostate cancer cohorts within the Health Professionals Follow-up Study (n = 249) and the Physicians' Health Study (n = 153) as well as expectantly managed patients in the Swedish Watchful Waiting Study (n = 338). The expression of squalene monooxygenase (SQLE) was associated with lethal cancer in all three cohorts. Men with high SQLE expression (>1 standard deviation above the mean) were 8.3 times (95% confidence interval, 3.5 to 19.7) more likely to have lethal cancer despite therapy compared with men with the mean level of SQLE expression. Absolute SQLE expression was associated with lethal cancer independently from Gleason grade and stage, as was a SQLE expression ratio in tumor versus surrounding benign prostate tissue. Higher SQLE expression was tightly associated with increased histologic markers of angiogenesis. Collectively, this study establishes the prognostic value of intratumoral cholesterol synthesis as measured via SQLE, its second rate-limiting enzyme. SQLE expression at cancer diagnosis is prognostic for lethal prostate cancer both after curative-intent prostatectomy and in a watchful waiting setting, possibly by facilitating micrometastatic disease.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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Onkologi
Oncology

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