Prediagnostic Serum Levels of Fatty Acid Metabolites and Risk of Ovarian Cancer in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.


Journal

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
ISSN: 1538-7755
Titre abrégé: Cancer Epidemiol Biomarkers Prev
Pays: United States
ID NLM: 9200608

Informations de publication

Date de publication:
01 2019
Historique:
received: 11 05 2018
revised: 10 08 2018
accepted: 19 09 2018
pubmed: 29 9 2018
medline: 12 2 2020
entrez: 29 9 2018
Statut: ppublish

Résumé

Evidence suggests that inflammation increases risk for ovarian cancer. Aspirin has been shown to decrease ovarian cancer risk, though the mechanism is unknown. Studies of inflammatory markers, lipid molecules such as arachidonic acid, linoleic acid, and alpha-linoleic acid metabolites, and development of ovarian cancer are essential to understand the potential mechanisms. We conducted a nested case-control study (157 cases/156 matched controls) within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Unconditional logistic regression was used to estimate the association between prediagnostic serum levels of 31 arachidonic acid/linoleic acid/alpha-linoleic acid metabolites and risk of ovarian cancer. Five of the 31 arachidonic acid/linoleic acid/alpha-linoleic acid (free fatty acids) metabolites were positively associated with ovarian cancer risk: 8-HETE [tertile 3 vs. 1: OR 2.53 (95% confidence interval [CI] 1.18-5.39), Women with increased levels of five fatty acid metabolites (8-HETE, 12,13-DHOME, 13-HODE, 9-HODE, and 9,12,13-THOME) were at increased risk of developing ovarian cancer in the ensuing decade. All five metabolites are derived from either arachidonic acid (8-HETE) or linoleic acid (12,13-DHOME, 13-HODE, 9-HODE, 9,12,13-THOME) via metabolism through the LOX/cytochrome P450 pathway. The identification of these risk-related fatty acid metabolites provides mechanistic insights into the etiology of ovarian cancer and indicates the direction for future research.

Sections du résumé

BACKGROUND
Evidence suggests that inflammation increases risk for ovarian cancer. Aspirin has been shown to decrease ovarian cancer risk, though the mechanism is unknown. Studies of inflammatory markers, lipid molecules such as arachidonic acid, linoleic acid, and alpha-linoleic acid metabolites, and development of ovarian cancer are essential to understand the potential mechanisms.
METHODS
We conducted a nested case-control study (157 cases/156 matched controls) within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Unconditional logistic regression was used to estimate the association between prediagnostic serum levels of 31 arachidonic acid/linoleic acid/alpha-linoleic acid metabolites and risk of ovarian cancer.
RESULTS
Five of the 31 arachidonic acid/linoleic acid/alpha-linoleic acid (free fatty acids) metabolites were positively associated with ovarian cancer risk: 8-HETE [tertile 3 vs. 1: OR 2.53 (95% confidence interval [CI] 1.18-5.39),
CONCLUSIONS
Women with increased levels of five fatty acid metabolites (8-HETE, 12,13-DHOME, 13-HODE, 9-HODE, and 9,12,13-THOME) were at increased risk of developing ovarian cancer in the ensuing decade. All five metabolites are derived from either arachidonic acid (8-HETE) or linoleic acid (12,13-DHOME, 13-HODE, 9-HODE, 9,12,13-THOME) via metabolism through the LOX/cytochrome P450 pathway.
IMPACT
The identification of these risk-related fatty acid metabolites provides mechanistic insights into the etiology of ovarian cancer and indicates the direction for future research.

Identifiants

pubmed: 30262599
pii: 1055-9965.EPI-18-0392
doi: 10.1158/1055-9965.EPI-18-0392
pmc: PMC6325018
mid: NIHMS1508188
doi:

Substances chimiques

Arachidonic Acids 0
Biomarkers, Tumor 0
Hydroxyeicosatetraenoic Acids 0
Linoleic Acids 0
13-hydroxy-9,11-octadecadienoic acid 5204-88-6
8-hydroxyeicosatetraenoic acid 73179-96-1

Types de publication

Journal Article Research Support, N.I.H., Intramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

189-197

Subventions

Organisme : Intramural NIH HHS
ID : Z01 ES025034-14
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA CP010152-19
Pays : United States

Informations de copyright

©2018 American Association for Cancer Research.

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Auteurs

Manila Hada (M)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. manila.hada@nih.gov.

Matthew L Edin (ML)

National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina.

Patricia Hartge (P)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Fred B Lih (FB)

National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina.

Nicolas Wentzensen (N)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Darryl C Zeldin (DC)

National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina.

Britton Trabert (B)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

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Classifications MeSH