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J Natl Cancer Inst. 2019 Oct 8. pii: djz195. doi: 10.1093/jnci/djz195. [Epub ahead of print]

Circulating Lysophosphatidylcholines, Phosphatidylcholines, Ceramides, and Sphingomyelins and Ovarian Cancer Risk: a 23-year Prospective Study.

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Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Broad Institute of Massachusetts Institute of Technology and Harvard, Boston, MA, USA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.



Experimental evidence supports a role of lipid dysregulation in ovarian cancer progression. We estimated associations with ovarian cancer risk for circulating levels of four lipid groups, previously hypothesized to be associated with ovarian cancer, measured 3-23 years before diagnosis.


Analyses were conducted among cases (N = 252) and matched controls (N = 252) from the Nurses' Health Studies. We used logistic regression adjusting for risk factors to investigate associations of lysophosphatidylcholines (LPC), phosphatidylcholines (PC), ceramides (CER), and sphingomyelins (SM) with ovarian cancer risk overall and by histotype. A modified Bonferroni approach (0.05/4=0.0125; 4 lipid groups) and the permutation-based Westfall and Young approach were used to account for testing multiple correlated hypotheses. Odds ratios (OR; 10th -90th percentile) and 95% confidence intervals of ovarian cancer risk were estimated. All statistical tests were two-sided.


SM sum was statistically significantly associated with ovarian cancer risk (OR(95%CI)=1.97(1.16-3.32); p-value=0.01/permutation-adjusted-p=0.20). C16:0 SM, C18:0 SM, C16:0 CER were suggestively associated with risk (ORs: 1.95-2.10; p-values: 0.004-0.01/permutation-adjusted-p: 0.08-0.21). SM sum, C16:0 SM, and C16:0 CER had stronger ORs among postmenopausal women (OR range: 2.16-3.22). ORs were similar for serous/poorly differentiated and endometrioid/clear cell tumors, although C18:1 LPC and LPC to PC ratio were suggestively inversely, while C18:0 SM was suggestively positively associated with risk of endometrioid/clear cell tumors. No individual metabolites were associated with risk when using the permutation-based approach.


Elevated levels of circulating SMs 3-23 years before diagnosis were associated with increased risk of ovarian cancer, regardless of histotype, with stronger associations among postmenopausal women. Further studies are required to validate and understand the role of lipid dysregulation in ovarian carcinogenesis.


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