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Evolving population-based statistics for rare epithelial ovarian cancers.

ABSTRACT: OBJECTIVE:To describe how population-based statistics for rare epithelial ovarian cancers are evolving. METHODS:This is a retrospective observational study examining the Surveillance, Epidemiology, and End Results Program from 1988 to 2016. Overall survival (OS) of clear cell (OCCC), mucinous (MOC), and low-grade serous (LGSOC) ovarian cancers were compared to high-grade serous ovarian cancer (HGSOC) by fitting a propensity score matching. RESULTS:Among 113,365 ovarian malignancies, 5780 OCCCs (5.1%), 7561 MOCs (6.7%), and 2021 LGSOCs (1.8%) were compared to 38,199 HGSOCs. OCCCs and MOCs were more likely to be diagnosed with stage I disease compared to HGSOC (57.0-59.5% versus 8.6%, P<0.001). For early-stage disease, OCCC (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.82-1.01) and MOC (HR 0.94, 95%CI 0.85-1.04) had similar OS to HGSOC whereas LGSOC had superior OS (HR 0.93, 95%CI 0.89-0.97) versus HGSOC. Conversely, for advanced-stage disease, OCCC (HR 1.42, 95%CI 1.32-1.53) and MOC (HR 1.11, 95%CI 1.09-1.13) had poorer OS whereas LGSOC (HR 0.86, 95%CI 0.84-0.89) had superior OS compared to HGSOC. OCCC (HR range, 1.92-2.45) and MOC (HR range, 1.73-2.22) had particularly poorer OS in the first three years following diagnosis compared to HGSOC. Population-level statistics for advanced-stage disease showed that 5-year OS rates have increased in HGSOC (16.9% to 36.8%, P<0.001) and LGSOC (50.8% to 66.4%, P=0.010); but remain unchanged for OCCC (21.0% to 28.2%, P=0.174) and MOC (21.4% to 16.5%, P=0.102). CONCLUSION:OCCC, MOC, and LGSOC comprise 2-7% of ovarian malignancies, have distinct characteristics and survival compared to HGSOC. While these rare tumors have a favorable to comparable prognosis in early-stage disease, disproportionally poor survival in advanced-stage OCCC and MOC highlights the need for further research into novel treatment strategies.

SUBMITTER: Matsuo K

PROVIDER: S-EPMC7526050 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundWith the advent of next-generation sequencing (NGS) technologies, researchers are now generating a deluge of data on high dimensional genomic variations, whose analysis is likely to reveal rare variants involved in the complex etiology of disease. Standing in the way of such discoveries, however, is the fact that statistics for rare variants are currently designed for use with population-based data. In this paper, we introduce a pedigree-based statistic specifically designed to test for rare variants in family-based data. The additional power of pedigree-based statistics stems from the fact that while rare variants related to diseases or traits of interest occur only infrequently in populations, in families with multiple affected individuals, such variants are enriched. Note that while the proposed statistic can be applied with and without statistical weighting, our simulations show that its power increases when weighting (WSS and VT) are applied.ResultsOur working hypothesis was that, since rare variants are concentrated in families with multiple affected individuals, pedigree-based statistics should detect rare variants more powerfully than population-based statistics. To evaluate how well our new pedigree-based statistics perform in association studies, we develop a general framework for sequence-based association studies capable of handling data from pedigrees of various types and also from unrelated individuals. In short, we developed a procedure for transforming population-based statistics into tests for family-based associations. Furthermore, we modify two existing tests, the weighted sum-square test and the variable-threshold test, and apply both to our family-based collapsing methods. We demonstrate that the new family-based tests are more powerful than corresponding population-based test and they generate a reasonable type I error rate.To demonstrate feasibility, we apply the newly developed tests to a pedigree-based GWAS data set from the Framingham Heart Study (FHS). FHS-GWAS data contain approximately 5000 uncommon variants with frequencies less than 0.05. Potential association findings in these data demonstrate the feasibility of the software PB-STAR (note, PB-STAR is now freely available to the public).ConclusionOur tests show that when analyzing for rare variants, a pedigree-based design is more powerful than a population-based case-control design. We further demonstrate that a pedigree-based statistic's power to detect rare variants increases in direct relation to the proportion of affected individuals within the pedigree.

Project description:In 2018, there will be approximately 22,240 new cases of ovarian cancer diagnosed and 14,070 ovarian cancer deaths in the United States. Herein, the American Cancer Society provides an overview of ovarian cancer occurrence based on incidence data from nationwide population-based cancer registries and mortality data from the National Center for Health Statistics. The status of early detection strategies is also reviewed. In the United States, the overall ovarian cancer incidence rate declined from 1985 (16.6 per 100,000) to 2014 (11.8 per 100,000) by 29% and the mortality rate declined between 1976 (10.0 per 100,000) and 2015 (6.7 per 100,000) by 33%. Ovarian cancer encompasses a heterogenous group of malignancies that vary in etiology, molecular biology, and numerous other characteristics. Ninety percent of ovarian cancers are epithelial, the most common being serous carcinoma, for which incidence is highest in non-Hispanic whites (NHWs) (5.2 per 100,000) and lowest in non-Hispanic blacks (NHBs) and Asians/Pacific Islanders (APIs) (3.4 per 100,000). Notably, however, APIs have the highest incidence of endometrioid and clear cell carcinomas, which occur at younger ages and help explain comparable epithelial cancer incidence for APIs and NHWs younger than 55 years. Most serous carcinomas are diagnosed at stage III (51%) or IV (29%), for which the 5-year cause-specific survival for patients diagnosed during 2007 through 2013 was 42% and 26%, respectively. For all stages of epithelial cancer combined, 5-year survival is highest in APIs (57%) and lowest in NHBs (35%), who have the lowest survival for almost every stage of diagnosis across cancer subtypes. Moreover, survival has plateaued in NHBs for decades despite increasing in NHWs, from 40% for cases diagnosed during 1992 through 1994 to 47% during 2007 through 2013. Progress in reducing ovarian cancer incidence and mortality can be accelerated by reducing racial disparities and furthering knowledge of etiology and tumorigenesis to facilitate strategies for prevention and early detection. CA Cancer J Clin 2018;68:284-296. © 2018 American Cancer Society.

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Evolving population-based statistics for rare epithelial ovarian cancers.

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