Cancer
Plasma metabolomic profiles associated with breastfeeding history and subsequent ovarian cancer risk Jennifer Mongiovi* Jennifer Mongiovi Julian Avila Pacheco Nan Lin Mary K. Townsend Britton Trabert Nicolas Wentzensen Nicole Prince Jessica A. Lasky-Su A. Heather Eliassen Clary B. Clish Shelley S. Tworoger Oana A. Zeleznik Naoko Sasamoto
Breastfeeding may reduce risk of epithelial ovarian cancer (EOC), but the biological mechanisms remain unclear. We identified plasma metabolites associated with breastfeeding history and explored their relationships with EOC.
Data included 606 plasma metabolites from 9,904 parous women in the Nurses’ Health Studies (NHS/NHSII). Associations between breastfeeding (≤6 months, >6 to <12 months, ≥12 months) and metabolite levels were assessed using multivariable linear regression and replicated in 663 participants from the Vitamin D Antenatal Asthma Reduction Trial (VDAART). Metabolite set enrichment analysis (MSEA) identified metabolite classes associated with breastfeeding. False discovery rate (FDR) correction addressed multiple testing. To examine the relationship between breastfeeding-related metabolites and EOC, we used a metabolite-based breastfeeding score (MBS) previously derived and replicated among 4,349 NHS/NHSII and 2,088 Women’s Health Initiative participants. The MBS included 6 metabolites (3 triglycerides, cotinine, N-acetyltryptophan, hippurate). Multivariable linear regression and meta-analysis were used to assess the association of the MBS with EOC risk in 436 NHS/NHSII and 412 Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial participants.
We observed positive associations for 12 metabolites with breastfeeding ≥12 months (FDR<0.05; C24:1 ceramide, C14:0 cholesteryl ester, indole-3-proprionate, threitol, uracil, organic acids, phosphatidylethanolamines) and negative associations for threonine and myristoleic acid. Similar associations were observed in the VDAART cohort for all available metabolites except serine. MSEA revealed positive associations with phosphatidylcholines and phosphatidylethanolamines. Comparing the highest quartile of MBS to the lowest, we observed 43% lower odds of EOC (OR: 0.57; 95% CI: 0.33-0.99).
These findings suggest that breastfeeding influences metabolic pathways long-term, potentially reducing EOC risk.