A Prospective Analysis of Circulating Plasma Metabolites Associated with Ovarian Cancer Risk
Abstract
Ovarian cancer has few known risk factors, hampering identification of high-risk women. We assessed the association of prediagnostic plasma metabolites (N = 420) with risk of epithelial ovarian cancer, including both borderline and invasive tumors. A total of 252 cases and 252 matched controls from the Nurses' Health Studies were included. Multivariable logistic regression was used to estimate ORs and 95% confidence intervals (CI), comparing the 90th–10th percentile in metabolite levels, using the permutation-based Westfall and Young approach to account for testing multiple correlated hypotheses. Weighted gene coexpression network analysis (WGCNA; n = 10 metabolite modules) and metabolite set enrichment analysis (n = 23 metabolite classes) were also evaluated. An increase in pseudouridine levels from the 10th to the 90th percentile was associated with a 2.5-fold increased risk of overall ovarian cancer (OR = 2.56; 95% CI, 1.48–4.45; P = 0.001/adjusted P = 0.15); a similar risk estimate was observed for serous/poorly differentiated tumors (n = 176 cases; comparable OR = 2.38; 95% CI, 1.33–4.32; P = 0.004/adjusted P = 0.55). For nonserous tumors (n = 34 cases), pseudouridine and C36:2 phosphatidylcholine plasmalogen had the strongest statistical associations (OR = 9.84; 95% CI, 2.89–37.82; P < 0.001/adjusted P = 0.07; and OR = 0.11; 95% CI, 0.03–0.35; P < 0.001/adjusted P = 0.06, respectively). Five WGCNA modules and 9 classes were associated with risk overall at FDR ≤ 0.20. Triacylglycerols (TAG) showed heterogeneity by tumor aggressiveness (case-only heterogeneity P < 0.0001). The TAG association with risk overall and serous tumors differed by acyl carbon content and saturation. In summary, this study suggests that pseudouridine may be a novel risk factor for ovarian cancer and that TAGs may also be important, particularly for rapidly fatal tumors, with associations differing by structural features.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 13, 2020
- Source ID
- 10.1158/0008-5472.can-19-2567
Entities
People
- A Heather Eliassen
- Amy Deik
- Bernard A. Rosner
- Clary B Clish
- Daniel S. Hitchcock
- Elizabeth M Poole
- Julian Avila
- Kevin Bullock
- Oana A Zeleznik
- Peter Kraft
- Sarah Jeanfavre
- Shelley S. Tworoger
Organizations
- H. Lee Moffitt Cancer Center & Research Institute
- Harvard Medical School
- Harvard University
- National Cancer Institute
- United States Department of Defense