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Article ; Online: Invited Commentary: Relationship Between Ovulation and Markers of Systemic Inflammation Versus Markers of Localized Inflammation.

Schildkraut, Joellen M

2020 Volume 189, Issue 7, Page(s) 671–673

Abstract: In this issue of the American Journal of Epidemiology, Huang et al. (Am J Epidemiol. 2020;189(7):660-670) report an inverse relationship between lifetime ovulatory years (LOY) and circulating levels of C-reactive protein (CRP), counter to their ... ...

Abstract	In this issue of the American Journal of Epidemiology, Huang et al. (Am J Epidemiol. 2020;189(7):660-670) report an inverse relationship between lifetime ovulatory years (LOY) and circulating levels of C-reactive protein (CRP), counter to their hypothesis. CRP is a nonspecific systemic marker of chronic inflammation, and there is evidence that there are other drivers of systemic inflammation as measured by CRP. There also is a body of evidence supporting the possibility that ovulation may be responsible for a localized inflammatory response. Because ovarian cancer is the fifth most common cause of cancer death in women, preventive strategies are urgently needed. The findings of this report underscore the need for new research initiatives to determine the relationship between incessant ovulation and ovarian cancer risk in order to identify mechanisms of carcinogenesis.
MeSH term(s)	Biomarkers ; C-Reactive Protein/analysis ; Carcinoma, Ovarian Epithelial ; Female ; Humans ; Inflammation ; Ovarian Neoplasms ; Ovulation ; Risk Factors
Chemical Substances	Biomarkers ; C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2020-01-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	2937-3
ISSN	1476-6256 ; 0002-9262
ISSN (online)	1476-6256
ISSN	0002-9262
DOI	10.1093/aje/kwz265
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Article: Mapping inherited genetic variation with opposite effects on autoimmune disease and cancer identifies candidate drug targets associated with the anti-tumor immune response.

Chen, Junyu / Epstein, Michael P / Schildkraut, Joellen M / Kar, Siddhartha P

medRxiv : the preprint server for health sciences

2023

Abstract: Background: Germline alleles near genes that encode certain immune checkpoints (: Methods: Pairwise fixed effect cross-disorder meta-analyses combining genome-wide association studies (GWAS) for breast, prostate, ovarian and endometrial cancers (240, ... ...

Abstract	Background: Germline alleles near genes that encode certain immune checkpoints ( Methods: Pairwise fixed effect cross-disorder meta-analyses combining genome-wide association studies (GWAS) for breast, prostate, ovarian and endometrial cancers (240,540 cases/317,000 controls) and seven autoimmune/autoinflammatory diseases (112,631 cases/895,386 controls) coupled with Results: Meta-analyses followed by linkage disequilibrium clumping identified 312 unique, independent lead variants with P Conclusion: We provide population-scale germline genetic and functional genomic evidence to support further evaluation of the proteins encoded by
Language	English
Publishing date	2023-12-28
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.12.23.23300491
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Article ; Online: Racial/ethnic disparities in ovarian cancer research.

Peres, Lauren C / Schildkraut, Joellen M

Advances in cancer research

2020 Volume 146, Page(s) 1–21

Abstract: Ovarian cancer is one of the most fatal cancers diagnosed in women in the United States (U.S.). Data from national databases, including the Surveillance Epidemiology and End Results (SEER) program, show racial/ethnic differences in risk and survival of ... ...

Abstract	Ovarian cancer is one of the most fatal cancers diagnosed in women in the United States (U.S.). Data from national databases, including the Surveillance Epidemiology and End Results (SEER) program, show racial/ethnic differences in risk and survival of epithelial ovarian cancer with higher incidence among white women yet worse survival among African-American women compared to other racial/ethnic groups. The reasons for these differences are not well understood, but are likely multi-factorial. Epidemiologic studies suggest there may be some risk factor differences across racial/ethnic groups that would explain differences in the incidence of this rare and heterogeneous disease. Likewise, although data suggest that socioeconomic factors and access to care contribute to the disparity in ovarian cancer survival among African-American women, there are likely other contributing factors that have not as of yet been identified. Small sample sizes of minority women from individual studies do not provide adequate power to evaluate fully the contributions of environmental, genetic, and clinical factors associated with ovarian cancer risk and survival within these groups. Pooling existing data from individual epidemiologic studies has made a valuable contribution; however, new data collection is warranted to further our understanding of the underpinnings of the disparities in ovarian cancer that may lead to prevention and improved survival across all racial/ethnic groups.
MeSH term(s)	Delivery of Health Care, Integrated/standards ; Ethnic Groups/statistics & numerical data ; Female ; Healthcare Disparities/statistics & numerical data ; Humans ; Ovarian Neoplasms/diagnosis ; Ovarian Neoplasms/epidemiology ; Ovarian Neoplasms/therapy ; Prognosis ; SEER Program ; United States/epidemiology
Language	English
Publishing date	2020-02-24
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	127-2
ISSN	2162-5557 ; 0065-230X
ISSN (online)	2162-5557
ISSN	0065-230X
DOI	10.1016/bs.acr.2020.01.002
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Article ; Online: Predicted Proteome Association Studies of Breast, Prostate, Ovarian, and Endometrial Cancers Implicate Plasma Protein Regulation in Cancer Susceptibility.

Gregga, Isabelle / Pharoah, Paul D P / Gayther, Simon A / Manichaikul, Ani / Im, Hae Kyung / Kar, Siddhartha P / Schildkraut, Joellen M / Wheeler, Heather E

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

2023 Volume 32, Issue 9, Page(s) 1198–1207

Abstract: Background: Predicting protein levels from genotypes for proteome-wide association studies (PWAS) may provide insight into the mechanisms underlying cancer susceptibility.: Methods: We performed PWAS of breast, endometrial, ovarian, and prostate ... ...

Abstract	Background: Predicting protein levels from genotypes for proteome-wide association studies (PWAS) may provide insight into the mechanisms underlying cancer susceptibility. Methods: We performed PWAS of breast, endometrial, ovarian, and prostate cancers and their subtypes in several large European-ancestry discovery consortia (effective sample size: 237,483 cases/317,006 controls) and tested the results for replication in an independent European-ancestry GWAS (31,969 cases/410,350 controls). We performed PWAS using the cancer GWAS summary statistics and two sets of plasma protein prediction models, followed by colocalization analysis. Results: Using Atherosclerosis Risk in Communities (ARIC) models, we identified 93 protein-cancer associations [false discovery rate (FDR) < 0.05]. We then performed a meta-analysis of the discovery and replication PWAS, resulting in 61 significant protein-cancer associations (FDR < 0.05). Ten of 15 protein-cancer pairs that could be tested using Trans-Omics for Precision Medicine (TOPMed) protein prediction models replicated with the same directions of effect in both cancer GWAS (P < 0.05). To further support our results, we applied Bayesian colocalization analysis and found colocalized SNPs for SERPINA3 protein levels and prostate cancer (posterior probability, PP = 0.65) and SNUPN protein levels and breast cancer (PP = 0.62). Conclusions: We used PWAS to identify potential biomarkers of hormone-related cancer risk. SNPs in SERPINA3 and SNUPN did not reach genome-wide significance for cancer in the original GWAS, highlighting the power of PWAS for novel locus discovery, with the added advantage of providing directions of protein effect. Impact: PWAS and colocalization are promising methods to identify potential molecular mechanisms underlying complex traits.
MeSH term(s)	Male ; Female ; Humans ; Proteome/genetics ; Genetic Predisposition to Disease ; Prostate ; Bayes Theorem ; Genome-Wide Association Study ; Endometrial Neoplasms/genetics ; Prostatic Neoplasms/genetics ; Blood Proteins ; Polymorphism, Single Nucleotide
Chemical Substances	Proteome ; Blood Proteins
Language	English
Publishing date	2023-07-04
Publishing country	United States
Document type	Meta-Analysis ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1153420-5
ISSN	1538-7755 ; 1055-9965
ISSN (online)	1538-7755
ISSN	1055-9965
DOI	10.1158/1055-9965.EPI-23-0309
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Article ; Online: Endometrial cancer.

Schildkraut, Joellen M

Gynecologic oncology

2011 Volume 120, Issue 2, Page(s) 165–166

MeSH term(s)	Endometrial Neoplasms/etiology ; Endometrial Neoplasms/genetics ; Female ; Humans ; Life Style
Language	English
Publishing date	2011-02
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2011.01.001
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Article ; Online: Reply to 'Comment on 'Dairy, calcium, vitamin D and ovarian cancer risk in African-American women''.

Qin, Bo / Peres, Lauren C / Schildkraut, Joellen M / Bandera, Elisa V

British journal of cancer

2018 Volume 119, Issue 2, Page(s) 260–262

MeSH term(s)	African Americans ; Calcium ; Calcium, Dietary ; Female ; Humans ; Ovarian Neoplasms ; Vitamin D
Chemical Substances	Calcium, Dietary ; Vitamin D (1406-16-2) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2018-07-02
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-018-0163-1
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Article: Molecular subtypes of high-grade serous ovarian cancer across racial groups and gene expression platforms.

Davidson, Natalie R / Barnard, Mollie E / Hippen, Ariel A / Campbell, Amy / Johnson, Courtney E / Way, Gregory P / Dalley, Brian K / Berchuck, Andrew / Salas, Lucas A / Peres, Lauren C / Marks, Jeffrey R / Schildkraut, Joellen M / Greene, Casey S / Doherty, Jennifer A

bioRxiv : the preprint server for biology

2023

Abstract: Introduction: High-grade serous carcinoma (HGSC) gene expression subtypes are associated with differential survival. We characterized HGSC gene expression in Black individuals and considered whether gene expression differences by race may contribute to ... ...

Abstract	Introduction: High-grade serous carcinoma (HGSC) gene expression subtypes are associated with differential survival. We characterized HGSC gene expression in Black individuals and considered whether gene expression differences by race may contribute to poorer HGSC survival among Black versus non-Hispanic White individuals. Methods: We included newly generated RNA-Seq data from Black and White individuals, and array-based genotyping data from four existing studies of White and Japanese individuals. We assigned subtypes using K-means clustering. Cluster- and dataset-specific gene expression patterns were summarized by moderated t-scores. We compared cluster-specific gene expression patterns across datasets by calculating the correlation between the summarized vectors of moderated t-scores. Following mapping to The Cancer Genome Atlas (TCGA)-derived HGSC subtypes, we used Cox proportional hazards models to estimate subtype-specific survival by dataset. Results: Cluster-specific gene expression was similar across gene expression platforms. Comparing the Black study population to the White and Japanese study populations, the immunoreactive subtype was more common (39% versus 23%-28%) and the differentiated subtype less common (7% versus 22%-31%). Patterns of subtype-specific survival were similar between the Black and White populations with RNA-Seq data; compared to mesenchymal cases, the risk of death was similar for proliferative and differentiated cases and suggestively lower for immunoreactive cases (Black population HR=0.79 [0.55, 1.13], White population HR=0.86 [0.62, 1.19]). Conclusions: A single, platform-agnostic pipeline can be used to assign HGSC gene expression subtypes. While the observed prevalence of HGSC subtypes varied by race, subtype-specific survival was similar.
Language	English
Publishing date	2023-12-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.11.01.565179
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Article ; Online: Racial Differences in the Association of Endometriosis and Uterine Leiomyomas With the Risk of Ovarian Cancer.

Harris, Holly R / Peres, Lauren C / Johnson, Courtney E / Guertin, Kristin A / Beeghly, Alicia / Bandera, Elisa V / Bethea, Traci N / Joslin, Charlotte E / Wu, Anna H / Moorman, Patricia G / Ochs-Balcom, Heather M / Petrick, Jessica L / Setiawan, Veronica W / Rosenberg, Lynn / Schildkraut, Joellen M / Myers, Evan

Obstetrics and gynecology

2023 Volume 141, Issue 6, Page(s) 1124–1138

Abstract: Objective: To evaluate associations between endometriosis and uterine leiomyomas with ovarian cancer risk by race and the effect of hysterectomy on these associations.: Methods: We used data from four case-control studies and two case-control studies ...

Abstract	Objective: To evaluate associations between endometriosis and uterine leiomyomas with ovarian cancer risk by race and the effect of hysterectomy on these associations. Methods: We used data from four case-control studies and two case-control studies nested within prospective cohorts in the OCWAA (Ovarian Cancer in Women of African Ancestry) consortium. The study population included 3,124 Black participants and 5,458 White participants, of whom 1,008 Black participants and 2,237 White participants had ovarian cancer. Logistic regression was used to calculate odds ratios (ORs) and 95% CIs for the associations of endometriosis and leiomyomas with ovarian cancer risk, by race, stratified by histotype and hysterectomy. Results: The prevalences of endometriosis and leiomyomas were 6.4% and 43.2% among Black participants and 7.0% and 21.5% among White participants, respectively. Endometriosis was associated with an increased risk of endometrioid and clear-cell ovarian cancer in both racial groups (eg, OR for endometrioid tumors for Black and White participants 7.06 [95% CI 3.86-12.91] and 2.17 [95% CI 1.36-3.45], respectively, Phetereogeneity =.003). The association between endometriosis and ovarian cancer risk in White participants was stronger in those without hysterectomy, but no difference was observed in Black participants (all Pinteraction ≥.05). Leiomyomas were associated with an elevated risk of ovarian cancer only in those without hysterectomy in both Black (OR 1.34, 95% CI 1.11-1.62) and White (OR 1.22, 95% CI 1.05-1.41) participants (all Pinteraction ≥.05). Conclusions: Black and White participants with endometriosis had a higher risk of ovarian cancer, and hysterectomy modified this association among White participants. Leiomyomas were associated with an increased risk of ovarian cancer in both racial groups, with hysterectomy modifying the risk in both groups. Understanding how racial differences in access to care and treatment options (eg, hysterectomy) may help guide future risk reduction strategies.
MeSH term(s)	Humans ; Female ; Endometriosis/complications ; Risk Factors ; Prospective Studies ; Race Factors ; Ovarian Neoplasms/epidemiology ; Ovarian Neoplasms/complications ; Leiomyoma/complications ; Leiomyoma/epidemiology ; Hysterectomy
Language	English
Publishing date	2023-05-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	207330-4
ISSN	1873-233X ; 0029-7844
ISSN (online)	1873-233X
ISSN	0029-7844
DOI	10.1097/AOG.0000000000005191
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Article: The tumor multi-omic landscape of endometrial cancers developed on a germline genetic background of adiposity.

Richenberg, George / Francis, Amy / Owen, Carina N / Gray, Victoria / Robinson, Timothy / Gabriel, Aurélie Ag / Lawrenson, Kate / Crosbie, Emma J / Schildkraut, Joellen M / Mckay, James D / Gaunt, Tom R / Relton, Caroline L / Vincent, Emma E / Kar, Siddhartha P

medRxiv : the preprint server for health sciences

2023

Abstract: High body mass index (BMI) is a causal risk factor for endometrial cancer but the tumor molecular mechanisms affected by adiposity and their therapeutic relevance remain poorly understood. Here we characterize the tumor multi-omic landscape of ... ...

Abstract	High body mass index (BMI) is a causal risk factor for endometrial cancer but the tumor molecular mechanisms affected by adiposity and their therapeutic relevance remain poorly understood. Here we characterize the tumor multi-omic landscape of endometrial cancers that have developed on a background of lifelong germline genetic exposure to elevated BMI. We built a polygenic score (PGS) for BMI in women using data on independent, genome-wide significant variants associated with adult BMI in 434,794 women. We performed germline (blood) genotype quality control and imputation on data from 354 endometrial cancer cases from The Cancer Genome Atlas (TCGA). We assigned each case in this TCGA cohort their genetically predicted life-course BMI based on the BMI PGS. Multivariable generalized linear models adjusted for age, stage, microsatellite status and genetic principal components were used to test for associations between the BMI germline PGS and endometrial cancer tumor genome-wide genomic, transcriptomic, proteomic, epigenomic and immune traits in TCGA. High BMI germline PGS was associated with (i) upregulated tumor gene expression in the
Language	English
Publishing date	2023-10-10
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.10.09.23296765
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Article ; Online: Role of neighborhood context in ovarian cancer survival disparities: current research and future directions.

Gomez, Scarlett L / Chirikova, Ekaterina / McGuire, Valerie / Collin, Lindsay J / Dempsey, Lauren / Inamdar, Pushkar P / Lawson-Michod, Katherine / Peters, Edward S / Kushi, Lawrence H / Kavecansky, Juraj / Shariff-Marco, Salma / Peres, Lauren C / Terry, Paul / Bandera, Elisa V / Schildkraut, Joellen M / Doherty, Jennifer A / Lawson, Andrew

American journal of obstetrics and gynecology

2023 Volume 229, Issue 4, Page(s) 366–376.e8

Abstract: Ovarian cancer is the fifth leading cause of cancer-associated mortality among US women with survival disparities seen across race, ethnicity, and socioeconomic status, even after accounting for histology, stage, treatment, and other clinical factors. ... ...

Abstract	Ovarian cancer is the fifth leading cause of cancer-associated mortality among US women with survival disparities seen across race, ethnicity, and socioeconomic status, even after accounting for histology, stage, treatment, and other clinical factors. Neighborhood context can play an important role in ovarian cancer survival, and, to the extent to which minority racial and ethnic groups and populations of lower socioeconomic status are more likely to be segregated into neighborhoods with lower quality social, built, and physical environment, these contextual factors may be a critical component of ovarian cancer survival disparities. Understanding factors associated with ovarian cancer outcome disparities will allow clinicians to identify patients at risk for worse outcomes and point to measures, such as social support programs or transportation aid, that can help to ameliorate such disparities. However, research on the impact of neighborhood contextual factors in ovarian cancer survival and in disparities in ovarian cancer survival is limited. This commentary focuses on the following neighborhood contextual domains: structural and institutional context, social context, physical context represented by environmental exposures, built environment, rurality, and healthcare access. The research conducted to date is presented and clinical implications and recommendations for future interventions and studies to address disparities in ovarian cancer outcomes are proposed.
MeSH term(s)	Humans ; Female ; Socioeconomic Factors ; Ethnicity ; Social Class ; Ovarian Neoplasms/therapy ; Social Environment ; Healthcare Disparities
Language	English
Publishing date	2023-04-26
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	80016-8
ISSN	1097-6868 ; 0002-9378
ISSN (online)	1097-6868
ISSN	0002-9378
DOI	10.1016/j.ajog.2023.04.026
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