Valeria Pala

Prospective evaluation of 92 protein biomarkers for early detection of endometrial cancer

Abstract The human epididymis protein 4 (HE4) remains the best available endometrial cancer (EC) biomarker; however, its discrimination between cases and cancer‐free individuals is limited and might be improved when combined with other protein markers. We evaluated the discrimination capacity of 92 proteins as potential early detection biomarkers for EC in nested case–control studies in the European Prospective Investigation into Cancer and Nutrition (EPIC) (63 cases, 123 controls) and Janus (75 cases, 146 controls) cohorts, evaluating blood samples taken ≤2 years prior to diagnosis. Proteins were measured with the Olink Target 96 Oncology II panel assays. Areas under the receiver operating characteristic curves (AUCs) were calculated using logistic regression. The discrimination between cases and controls of top‐performing proteins was modest (EPIC: HE4, CA125, CAIX, and S100A4; Janus: HE4, CA125, FURIN, CXCL13, and IL6; AUC range: 0.65 [S100A4], 0.76 [HE4, EPIC] within 0 to <12 months of blood collection) and decreased as the time between blood draw and cancer diagnosis increased (12–24 months AUC range: 0.49 [S100A4], 0.69 [CA125, Janus]). The combination of these other markers with HE4 did not improve discrimination. HE4 and other candidate proteins had limited discrimination between EC cases and controls and hence do not appear to be useful for early detection of this disease in women at average population risk.

Ovarian Cancer Risk Factor Associations by Primary Anatomic Site: The Ovarian Cancer Cohort Consortium

Abstract Background: Epithelial ovarian, fallopian tube, and primary peritoneal cancers have shared developmental pathways. Few studies have prospectively examined heterogeneity in risk factor associations across these three anatomic sites. Methods: We identified 3,738 ovarian, 337 peritoneal, and 176 fallopian tube incident cancer cases in 891,731 women from 15 prospective cohorts in the Ovarian Cancer Cohort Consortium. Associations between 18 putative risk factors and risk of ovarian, peritoneal, and fallopian tube cancer, overall and for serous and high-grade serous tumors, were evaluated using competing risks Cox proportional hazards regression. Heterogeneity was assessed by likelihood ratio tests. Results: Most associations did not vary by tumor site (Phet ≥ 0.05). Associations between first pregnancy (Phet = 0.04), tubal ligation (Phet = 0.01), and early-adult (age 18–21 years) body mass index (BMI; Phet = 0.02) and risk differed between ovarian and peritoneal cancers. The association between early-adult BMI and risk further differed between peritoneal and fallopian tube cancer (Phet = 0.03). First pregnancy and tubal ligation were inversely associated with ovarian, but not peritoneal, cancer. Higher early-adult BMI was associated with higher risk of peritoneal, but not ovarian or fallopian tube, cancer. Patterns were generally similar when restricted to serous and high-grade serous cases. Conclusions: Ovarian, fallopian tube, and primary peritoneal cancers appear to have both shared and distinct etiologic pathways, although most risk factors appear to have similar associations by anatomic site. Impact: Further studies on the mechanisms underlying the differences in risk profiles may provide insights regarding the developmental origins of tumors arising in the peritoneal cavity and inform prevention efforts.