Laura D. Kubzansky

Prolactin and Risk of Epithelial Ovarian Cancer

Abstract Background: Prolactin is synthesized in the ovaries and may play a role in ovarian cancer etiology. One prior prospective study observed a suggestive positive association between prolactin levels and risk of ovarian cancer. Methods: We conducted a pooled case–control study of 703 cases and 864 matched controls nested within five prospective cohorts. We used unconditional logistic regression to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between prolactin and ovarian cancer risk. We examined heterogeneity by menopausal status at blood collection, body mass index (BMI), age, and histotype. Results: Among women with known menopausal status, we observed a positive trend in the association between prolactin and ovarian cancer risk (Ptrend = 0.045; OR, quartile 4 vs. 1 = 1.34; 95% CI = 0.97–1.85), but no significant association was observed for premenopausal or postmenopausal women individually (corresponding OR = 1.38; 95% CI = 0.74–2.58; Ptrend = 0.32 and OR = 1.41; 95% CI = 0.93–2.13; Ptrend = 0.08, respectively; Pheterogeneity = 0.91). In stratified analyses, we observed a positive association between prolactin and risk for women with BMI ≥ 25 kg/m2, but not BMI < 25 kg/m2 (corresponding OR = 2.68; 95% CI = 1.56–4.59; Ptrend < 0.01 and OR = 0.90; 95% CI = 0.58–1.40; Ptrend = 0.98, respectively; Pheterogeneity < 0.01). Associations did not vary by age, postmenopausal hormone therapy use, histotype, or time between blood draw and diagnosis. Conclusions: We found a trend between higher prolactin levels and increased ovarian cancer risk, especially among women with a BMI ≥ 25 kg/m2. Impact: This work supports a previous study linking higher prolactin with ovarian carcinogenesis in a high adiposity setting. Future work is needed to understand the mechanism underlying this association.

Circulating Biomarkers of Inflammation and Ovarian Cancer Risk in the Nurses' Health Studies

AbstractBackground:Chronic inflammation is a well-established mechanism of ovarian carcinogenesis; however, the specific immunogenic processes influencing ovarian tumor development remain unclear. In a case–control study nested within the Nurses' Health Study (NHS) and the NHSII, we examined the association between six inflammatory chemokines and cytokines [B-cell activating factor (BAFF), C-X-C motif chemokine ligand 13 (CXCL13), IL8, soluble(s)IL2-receptor-α(Rα), sIL6Rα] and epithelial ovarian cancer risk.Methods:Among 299 epithelial ovarian cancer cases and 334 matched controls, six inflammatory biomarkers were measured in plasma collected 1–24 years before diagnosis or index date using two custom multiplex Luminex panels. ORs and 95% confidence intervals (CI) were estimated for the association between each biomarker and risk using multivariable conditional logistic regression with adjustment for relevant confounders. We additionally assessed heterogeneity in the risk associations by histotype [high-grade serous carcinoma (HGSC) vs. non-HGSC], body mass index, smoking status, menopausal status, and aspirin use.Results:Women with the highest versus lowest quartile (Q) levels of CXCL13 had a 72% increased ovarian cancer risk (OR = 1.72; 95% CI = 1.04–2.83; Ptrend = 0.007). The positive association with CXCL13 was stronger in magnitude for non-HGSC, overweight or obese women, and postmenopausal women, although only menopausal status demonstrated statistically significant heterogeneity (Pinteraction = 0.04). The remaining biomarkers were not associated with risk.Conclusions:This first evidence that prediagnostic CXCL13, a B-cell chemoattractant, is associated with an increased risk of epithelial ovarian cancer expands current understanding of the role of inflammation in ovarian carcinogenesis.Impact:CXCL13 may represent a novel biomarker for ovarian cancer.

Timing of depression in relation to risk of ovarian cancer

Abstract Background Several studies have suggested that depression may be associated with increased risk of ovarian cancer. Less is known about whether timing matters regarding when depression occurs. To provide evidence for an etiologically relevant exposure period, we examined depression occurring during the time in which precursor lesions develop and progress to invasive carcinoma with the risk of developing ovarian cancer. Methods Using data from 2 prospective cohorts (1992-2015), we divided follow-up into consecutive 2-year periods for analytic purposes, referred to as “cancer ascertainment periods.” We estimated associations of depression in the 10 years before each cancer ascertainment period with incident cancer, using Cox proportional hazards models. Next, we estimated associations of depression occurring up to 18 years before each ascertainment period, in 2-year increments, with incident cancer. We adjusted for demographic, health, and behavioral factors. All tests of statistical significance were two-sided, with a P-value threshold of less than .05. Results Depression occurring in the 10 prior years was associated with 30% greater risk of cancer (hazard ratio [HR] = 1.30, 95% confidence interval = 1.15 to 1.46). Associations were similar in fully adjusted models (HR = 1.27). Depression occurring in the 14 years before ascertainment was associated with elevated risk, although only estimates for depression 0-2, 6-8, and 8-10 years before ascertainment reached statistical significance (HR range = 1.20-1.36). Conclusion Depression occurring up to 14 years before cancer ascertainment was associated with greater cancer risk. This is the time of precursor progression to invasive ovarian carcinoma, suggesting depression may be an ovarian cancer-promoting agent.

Caregiver burden and risk of epithelial ovarian cancer in the Nurses’ Health Studies

Abstract Psychosocial stress may increase ovarian cancer risk and accelerate disease progression. We examined the association between caregiver burden, a common stressor, and risk of epithelial ovarian cancer. We prospectively followed 67 724 women in the Nurses’ Health Study (1992-2012) and 70 720 women in the Nurses’ Health Study II (2001-2009) who answered questions on informal caregiving (ie, caregiving outside of work). Women who reported no informal caregiving were considered noncaregivers, while, among women who provided care outside of work, caregiver burden was categorized by time spent caregiving and perceived stress from caregiving. For the 34% of women who provided informal care for ≥15 hours per week, 42% described caregiving as moderately to extremely stressful. Pooled multivariate analyses indicated no difference in ovarian cancer risk for women providing ≥15 hours of care per week compared to noncaregivers (hazard ratio [HR] = 0.96; 95% confidence interval [CI], 0.79-1.18), and no association was evident for women who reported moderate or extreme stress from caregiving compared to noncaregivers (HR = 0.96; 95% CI, 0.75-1.22). Together with prior work evaluating job strain and ovarian cancer risk, our findings suggest that, when evaluating a stressor’s role in cancer risk, it is critical to consider how the stressor contributes to the overall experience of distress. This article is part of a Special Collection on Gynecological Cancer.