He/Him/His
Job Title
postdoctoral research fellow
Academic Rank
Fellow or Postdoc
Department
Obstetrics and Gynecology
Authors
Nan Lin, PhD*, Raji Balasubramanian, ScD, Heather A. Eliassen, ScD, Britton Trabert, PhD, Mary K. Townsend, PhD, Shelley S. Tworoger, PhD, Oana A. Zeleznik, PhD
Categories
Tags
Background
Ovarian cancer has few known risk factors, underscoring the need to identify additional ones. Chronic stress may influence ovarian cancer development. Metabolites, as end-products of metabolism, reflect genetic and environmental influences and are associated with chronic distress. We evaluated the association between a metabolite-based distress score (MDS) and ovarian cancer risk.
Methods
Our study includes two 1:1 matched case-control studies, one (N=594) within the Nurses’ Health Studies (NHS/NHSII) and another (N=348) within the PLCO trial. Metabolites were measured 3-27 years before diagnosis. Of the 20 MDS metabolites, we aligned 19 across batches for calculating the MDS. Odds ratios (OR) and confidence intervals (CI) for ovarian cancer were estimated for a one standard deviation (SD) increase in MDS and its individual metabolites using conditional logistic regression, accounting for matching factors (model 1). Model 2 adjusted for ovarian cancer risk factors including menopausal status, race, and family history. Results from NHS and PLCO were combined using meta-analysis.
Results
A 1-SD increase in MDS level was not statistically significantly associated with ovarian cancer risk in NHS and PLCO, however point estimates were in the expected directions (OR=1.10;95%CI=0.93-1.31,p=0.27 and OR=1.07;95%CI=0.89-1.28,p=0.49). This pattern was also observed in the fully adjusted meta-analysis (OR=1.09,95%CI=0.96-1.23,p=0.20). Among the 13 MDS constituent metabolites, a 1-SD increase in 3-methylxanthine was associated with a 15% increased ovarian cancer risk in the meta-analysis (OR=1.15,95%CI=1.00-1.31,p=0.047;NHS:OR=1.12;CI=0.94-1.32,p=0.20;PLCO:OR=1.21;CI=0.96-1.52,p=0.10) with statistical significance. Findings did not change when we restricted to postmenopausal women.
Conclusion
In two independent studies, higher circulating MDS levels were associated with a modest, though non-significant, increase in ovarian cancer risk, supporting our hypothesis. Additional analyses examining lifestyle and behavioral impacts on MDS and ovarian cancer risk are ongoing. Findings suggest metabolic dysregulation linked to chronic distress may be a novel risk factor for ovarian cancer, with 3-methylxanthine potentially playing a role in this association.
