A Comprehensive Epithelial Tubo-Ovarian Cancer Risk Prediction Model Incorporating Genetic and Epidemiological Risk Factors

AbstractBackgroundEpithelial tubo-ovarian cancer (EOC) has high mortality partly due to late diagnosis. Prevention is available but may be associated with adverse effects. Several genetic and epidemiological risk factors (RFs) for EOC have been identified. A multifactorial risk model can help identify females at higher risk who could benefit from targeted screening and prevention.MethodsWe developed an EOC risk model incorporating the effects of family history (FH), pathogenic variants (PVs) in BRCA1, BRCA2, RAD51C, RAD51D and BRIP1, a polygenic risk score (PRS) and the effects of RFs. The model was validated in a nested case-control sample of 1961 females from UKCTOCS (374 incident cases).ResultsEstimated lifetime risks in the general population vary from 0.5% to 4.6% for the 1st to 99th percentiles of the EOC risk-distribution. The corresponding range for females with an affected first-degree relative is 1.9% to 10.3%. RFs provided the widest distribution followed by the PRS. In the external validation, absolute and relative 5-year risks were well-calibrated in quintiles of predicted risk.ConclusionThis multifactorial risk model can facilitate stratification, in particular among females with FH of cancer and/or moderate- and high-risk PVs. The model is available via the CanRisk Tool (www.canrisk.org).

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Comprehensive epithelial tubo-ovarian cancer risk prediction model incorporating genetic and epidemiological risk factors

Journal of Medical Genetics ◽

10.1136/jmedgenet-2021-107904 ◽

2021 ◽

pp. jmedgenet-2021-107904

Author(s):

Andrew Lee ◽

Xin Yang ◽

Jonathan Tyrer ◽

Aleksandra Gentry-Maharaj ◽

Andy Ryan ◽

...

Keyword(s):

Risk Factors ◽

Ovarian Cancer ◽

Risk Model ◽

European Ancestry ◽

Polygenic Risk Score ◽

Ovarian Cancer Risk ◽

Degree Relative ◽

Pathogenic Variants ◽

Risk Distribution ◽

Epidemiological Risk

BackgroundEpithelial tubo-ovarian cancer (EOC) has high mortality partly due to late diagnosis. Prevention is available but may be associated with adverse effects. A multifactorial risk model based on known genetic and epidemiological risk factors (RFs) for EOC can help identify women at higher risk who could benefit from targeted screening and prevention.MethodsWe developed a multifactorial EOC risk model for women of European ancestry incorporating the effects of pathogenic variants (PVs) in BRCA1, BRCA2, RAD51C, RAD51D and BRIP1, a Polygenic Risk Score (PRS) of arbitrary size, the effects of RFs and explicit family history (FH) using a synthetic model approach. The PRS, PV and RFs were assumed to act multiplicatively.ResultsBased on a currently available PRS for EOC that explains 5% of the EOC polygenic variance, the estimated lifetime risks under the multifactorial model in the general population vary from 0.5% to 4.6% for the first to 99th percentiles of the EOC risk distribution. The corresponding range for women with an affected first-degree relative is 1.9%–10.3%. Based on the combined risk distribution, 33% of RAD51D PV carriers are expected to have a lifetime EOC risk of less than 10%. RFs provided the widest distribution, followed by the PRS. In an independent partial model validation, absolute and relative 5-year risks were well calibrated in quintiles of predicted risk.ConclusionThis multifactorial risk model can facilitate stratification, in particular among women with FH of cancer and/or moderate-risk and high-risk PVs. The model is available via the CanRisk Tool (www.canrisk.org).

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Ovarian cancer risk model needs a more meaningful clinical parameter

BMJ ◽

10.1136/bmj.g6689 ◽

2014 ◽

Vol 349 (nov18 9) ◽

pp. g6689-g6689

Author(s):

F. J. Candido-dos-Reis

Keyword(s):

Ovarian Cancer ◽

Cancer Risk ◽

Risk Model ◽

Clinical Parameter ◽

Ovarian Cancer Risk

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Estrogen Receptor-β Expression of Ovarian Tumors and Its Association with Ovarian Cancer Risk Factors

Cancer Epidemiology Biomarkers & Prevention ◽

10.1158/1055-9965.epi-20-0618 ◽

2020 ◽

Vol 29 (11) ◽

pp. 2211-2219

Author(s):

Amy L. Shafrir ◽

Ana Babic ◽

Margaret Gates Kuliszewski ◽

Megan S. Rice ◽

Mary K. Townsend ◽

...

Keyword(s):

Risk Factors ◽

Ovarian Cancer ◽

Estrogen Receptor ◽

Cancer Risk ◽

Ovarian Tumors ◽

Estrogen Receptor Β ◽

Ovarian Cancer Risk ◽

Cancer Risk Factors

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Appraising the role of previously reported risk factors in epithelial ovarian cancer risk: A Mendelian randomization analysis

PLoS Medicine ◽

10.1371/journal.pmed.1002893 ◽

2019 ◽

Vol 16 (8) ◽

pp. e1002893 ◽

Cited By ~ 18

Author(s):

James Yarmolinsky ◽

Caroline L. Relton ◽

Artitaya Lophatananon ◽

Kenneth Muir ◽

Usha Menon ◽

...

Keyword(s):

Risk Factors ◽

Ovarian Cancer ◽

Cancer Risk ◽

Epithelial Ovarian Cancer ◽

Mendelian Randomization ◽

Ovarian Cancer Risk ◽

Mendelian Randomization Analysis ◽

Randomization Analysis

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Ovarian cancer risk factors by tumor dominance, a surrogate for cell of origin

International Journal of Cancer ◽

10.1002/ijc.28064 ◽

2013 ◽

Vol 133 (3) ◽

pp. 730-739 ◽

Cited By ~ 17

Author(s):

Joanne Kotsopoulos ◽

Kathryn L. Terry ◽

Elizabeth M. Poole ◽

Bernard Rosner ◽

Megan A. Murphy ◽

...

Keyword(s):

Risk Factors ◽

Ovarian Cancer ◽

Cancer Risk ◽

Ovarian Cancer Risk ◽

Cell Of Origin ◽

Cancer Risk Factors

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Abstract 854: Ovarian cancer risk factors by histologic subtypes: evidence for etiologic heterogeneity

10.1158/1538-7445.am2015-854 ◽

2015 ◽

Author(s):

Nicolas A. Wentzensen ◽

Elizabeth Poole ◽

Alan A. Arslan ◽

Alpa V. Patel ◽

V Wendy Setiawan ◽

...

Keyword(s):

Risk Factors ◽

Ovarian Cancer ◽

Cancer Risk ◽

Ovarian Cancer Risk ◽

Cancer Risk Factors ◽

Etiologic Heterogeneity ◽

Histologic Subtypes

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Abstract A107: Ovarian cancer risk factors by tumor dominance, a surrogate for cell of origin

10.1158/1940-6207.prev-11-a107 ◽

2011 ◽

Author(s):

Kathryn L. Terry ◽

Megan Murphy ◽

Susan E. Hankinson ◽

Christopher P. Crum ◽

Daniel W. Cramer ◽

...

Keyword(s):

Risk Factors ◽

Ovarian Cancer ◽

Cancer Risk ◽

Ovarian Cancer Risk ◽

Cell Of Origin ◽

Cancer Risk Factors

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Refusal of recommended chemotherapy for ovarian cancer: Risk factors and outcomes, a National Cancer Database study

Gynecologic Oncology ◽

10.1016/j.ygyno.2015.01.467 ◽

2015 ◽

Vol 137 ◽

pp. 186

Author(s):

J.F. Lin ◽

B.A. Cliby ◽

G.S. Leiserowitz ◽

A.I. Tergas ◽

R.E. Bristow ◽

...

Keyword(s):

Risk Factors ◽

Ovarian Cancer ◽

Cancer Risk ◽

Ovarian Cancer Risk ◽

National Cancer Database ◽

Cancer Risk Factors ◽

Database Study

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Circulating Vitamin D and Risk of Epithelial Ovarian Cancer

Journal of Oncology ◽

10.1155/2009/672492 ◽

2009 ◽

Vol 2009 ◽

pp. 1-8 ◽

Cited By ~ 17

Author(s):

Alan A. Arslan ◽

Tess V. Clendenen ◽

Karen L. Koenig ◽

Johan Hultdin ◽

Kerstin Enquist ◽

...

Keyword(s):

Ovarian Cancer ◽

New York ◽

Vitamin D ◽

Epithelial Ovarian Cancer ◽

Cohort Analysis ◽

Health Study ◽

Ovarian Cancer Risk ◽

New York University ◽

Disease Study ◽

Incident Cases

We conducted a nested case-control study within two prospective cohorts, the New York University Women's Health Study and the Northern Sweden Health and Disease Study, to examine the association between prediagnostic circulating levels of 25-hydroxy vitamin D (25(OH)D) and the risk of subsequent invasive epithelial ovarian cancer (EOC). The 25(OH)D levels were measured in serum or plasma from 170 incident cases of EOC and 373 matched controls. Overall, circulating 25(OH)D levels were not associated with the risk of EOC in combined cohort analysis: adjusted OR for the top tertile versus the reference tertile, 1.09 (95% CI, 0.59–2.01). In addition, there was no evidence of an interaction effect betweenVDRSNP genotype or haplotype and circulating 25(OH)D levels in relation to ovarian cancer risk, although more complex gene-environment interactions may exist.

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