Dataset Information

Risk Prediction for Epithelial Ovarian Cancer in 11 United States-Based Case-Control Studies: Incorporation of Epidemiologic Risk Factors and 17 Confirmed Genetic Loci.

ABSTRACT: Previously developed models for predicting absolute risk of invasive epithelial ovarian cancer have included a limited number of risk factors and have had low discriminatory power (area under the receiver operating characteristic curve (AUC) < 0.60). Because of this, we developed and internally validated a relative risk prediction model that incorporates 17 established epidemiologic risk factors and 17 genome-wide significant single nucleotide polymorphisms (SNPs) using data from 11 case-control studies in the United States (5,793 cases; 9,512 controls) from the Ovarian Cancer Association Consortium (data accrued from 1992 to 2010). We developed a hierarchical logistic regression model for predicting case-control status that included imputation of missing data. We randomly divided the data into an 80% training sample and used the remaining 20% for model evaluation. The AUC for the full model was 0.664. A reduced model without SNPs performed similarly (AUC = 0.649). Both models performed better than a baseline model that included age and study site only (AUC = 0.563). The best predictive power was obtained in the full model among women younger than 50 years of age (AUC = 0.714); however, the addition of SNPs increased the AUC the most for women older than 50 years of age (AUC = 0.638 vs. 0.616). Adapting this improved model to estimate absolute risk and evaluating it in prospective data sets is warranted.

SUBMITTER: Clyde MA

PROVIDER: S-EPMC5065620 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Risk Prediction for Epithelial Ovarian Cancer in 11 United States-Based Case-Control Studies: Incorporation of Epidemiologic Risk Factors and 17 Confirmed Genetic Loci.

Clyde Merlise A MA Palmieri Weber Rachel R Iversen Edwin S ES Poole Elizabeth M EM Doherty Jennifer A JA Goodman Marc T MT Ness Roberta B RB Risch Harvey A HA Rossing Mary Anne MA Terry Kathryn L KL Wentzensen Nicolas N Whittemore Alice S AS Anton-Culver Hoda H Bandera Elisa V EV Berchuck Andrew A Carney Michael E ME Cramer Daniel W DW Cunningham Julie M JM Cushing-Haugen Kara L KL Edwards Robert P RP Fridley Brooke L BL Goode Ellen L EL Lurie Galina G McGuire Valerie V Modugno Francesmary F Moysich Kirsten B KB Olson Sara H SH Pearce Celeste Leigh CL Pike Malcolm C MC Rothstein Joseph H JH Sellers Thomas A TA Sieh Weiva W Stram Daniel D Thompson Pamela J PJ Vierkant Robert A RA Wicklund Kristine G KG Wu Anna H AH Ziogas Argyrios A Tworoger Shelley S SS Schildkraut Joellen M JM

American journal of epidemiology 20161003 8

Previously developed models for predicting absolute risk of invasive epithelial ovarian cancer have included a limited number of risk factors and have had low discriminatory power (area under the receiver operating characteristic curve (AUC) < 0.60). Because of this, we developed and internally validated a relative risk prediction model that incorporates 17 established epidemiologic risk factors and 17 genome-wide significant single nucleotide polymorphisms (SNPs) using data from 11 case-control ...[more]

PMID: 27698005

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Project description:BackgroundBiliary tract cancer (BTC) includes intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer (AVC). Although BTC is rare in the US, incidence is increasing and elevated in certain populations. This study examined BTC epidemiology in the US by age, sex, race/ethnicity, geographic region, and anatomic site.MethodsBTC incidence, prevalence, mortality, and survival from 2001 to 2015 were evaluated using the National Cancer Institute's Surveillance, Epidemiology, and End Results Program and the Centers for Disease Control and Prevention's National Program of Cancer Registries databases. Incidence and mortality rates were calculated and reported as age-standardized rates. Data were assessed by age, anatomic sites, geographic region, and race/ethnicity, and a joinpoint regression model was used to predict trends for age-adjusted BTC incidence and mortality rates.ResultsBTC incidence increased during the study period (annual percent change = 1.76, 95% confidence interval [1.59-1.92]), with the highest increase in ICC (6.65 [6.11-7.19]). Incidence of unspecified BTC initially increased but has recently begun to drop. Hispanic, Asian/Pacific Islander, Black, or American Indian/Alaska Native race/ethnicity was associated with higher BTC mortality rates than White race/ethnicity. Patients with ICC had the highest mortality rate (age-standardized rate = 1.87/100,000 person-years [1.85-1.88]). Five-year survival was 15.2% for all BTC, ranging from 8.5% (ICC) to 34.5% (AVC), and patients with distant disease at diagnosis had lower survival (3%) compared with those with regional (19.1%) or locally advanced disease (31.5%).ConclusionsBTC incidence increased, survival was low across all subtypes, and mortality was greatest in patients with ICC. This underscores the serious, increasing unmet need among patients with BTC. Treatment options are limited, although clinical studies investigating immunotherapy, targeted therapies, and alternative chemotherapy combinations are ongoing. Epidemiological insights may improve patient care and inform the integration of novel therapies for BTC.

Project description:Evidence suggesting that high-grade serous ovarian cancers originate in the fallopian tubes has led to the emergence of opportunistic salpingectomy (OS) as an approach to reduce ovarian-cancer risk. In the U.S., some national societies now recommend OS in place of tubal ligation for sterilization or during a benign hysterectomy in average-risk women. However, limited data exist on the dissemination of OS in clinical practice. We examined the uptake and predictors of OS in a nationwide sample of inpatient and outpatient claims (N = 48,231,235) from 2010 to 2017. Incidence rates of OS were calculated, and an interrupted time-series analysis was used to quantify changes in rates before (2010-2013) and after (2015-2017) national guideline release. Predictors of OS use were examined using Poisson regression. From 2010 to 2017, the age-adjusted incidence rate of OS for sterilization and OS during hysterectomy increased 17.8-fold [95% confidence interval (CI), 16.2-19.5] and 7.6-fold (95% CI, 5.5-10.4), respectively. The rapid increase (age-adjusted increase in quarterly rates of between 109% and 250%) coincided with the time of national guideline release. In multivariable-adjusted analyses, OS use was more common in young women and varied significantly by geographic region, rurality, family history/genetic susceptibility, surgical indication, inpatient/outpatient setting, and underlying comorbidities. Similar differences in OS uptake were noted in analyses limited to women with a family history/genetic susceptibility to breast/ovarian cancer. Our results highlight significant differences in OS uptake in both high- and average-risk women. Defining subsets of women who would benefit most from OS and identifying barriers to equitable OS uptake is needed. PREVENTION RELEVANCE: Opportunistic salpingectomy for ovarian-cancer risk reduction has been rapidly adopted in the U.S., with significant variation in uptake by demographic and clinical factors. Studies examining barriers to opportunistic salpingectomy access and the long-term effectiveness and potential adverse effects of opportunistic salpingectomy are needed.

Dataset Information

Risk Prediction for Epithelial Ovarian Cancer in 11 United States-Based Case-Control Studies: Incorporation of Epidemiologic Risk Factors and 17 Confirmed Genetic Loci.

Publications

Risk Prediction for Epithelial Ovarian Cancer in 11 United States-Based Case-Control Studies: Incorporation of Epidemiologic Risk Factors and 17 Confirmed Genetic Loci.

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