Circulating Biomarkers of Inflammation and Ovarian Cancer Risk in the Nurses' Health Studies
Year: 2021
Type: article
Study design: Observational Study
Abstract: Background: 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.
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1269185591, Initiation and Evolution of the Ovarian Cancer Microenvironment, Biochemical Markers in the nurses' Health Study Cohort, Dietary and Hormonal Determinants of Cancer in Women, G459566519, The Role of Inflammation in the Racial Disparities in Ovarian Cancer Survival, Long Term Multidisciplinary Study of Cancer in Women: The Nurses Health Study, Premenopausal Hormone Levels and Risk of Breast Cancer, G9000019617, Life Course Cancer Epidemiology Cohort in Women, Crosstalk between butyrophilins and gamma delta T cells in human cancer
OpenAlex ID: W3128376719