African American Cancer Epidemiology Study Research Articles

Prediagnostic Proinflammatory Dietary Potential Is Associated with All-Cause Mortality among African-American Women with High-Grade Serous Ovarian Carcinoma

Chronic inflammation is associated with ovarian carcinogenesis; yet, the impact of inflammatory-related exposures on outcomes has been understudied. Given the poor survival of women diagnosed with ovarian cancer, especially African-Americans, we examined whether diet-associated inflammation, a modifiable source of chronic systemic inflammation measured by the dietary inflammatory index (DII), was associated with all-cause mortality among African-American women with ovarian carcinoma. Data were available from 490 ovarian carcinoma patients enrolled in a population-based case-control study of African-American women with ovarian cancer, the African-American Cancer Epidemiology Study. Energy-adjusted DII (E-DII) scores were calculated based on prediagnostic dietary intake of foods alone or foods and supplements, which was self-reported using the 2005 Block Food Frequency Questionnaire. Cox proportional hazards regression was used to estimate risk of mortality overall and for the most common histotype, high-grade serous carcinoma. Additionally, we assessed interaction by age at diagnosis and smoking status. Women included in this study had a median age of 57 y, and the majority of women were obese (58%), had late-stage disease (Stage III or IV, 66%), and had high-grade serous carcinoma (64%). Greater E-DII scores including supplements (indicating greater inflammatory potential) were associated with an increased risk of mortality among women with high-grade serous carcinoma (HR1-unit change: 1.08; 95% CI: 1.01, 1.17). Similar associations were observed for the E-DII excluding supplements, although not statistically significant (HR1-unit change: 1.07; 95% CI: 0.97, 1.17). There was an interaction by smoking status, where the positive association with mortality was present only among ever smokers (HRQuartile 4/Quartile 1: 2.36; 95% CI: 1.21, 4.60) but not among never smokers. Greater inflammatory potential of prediagnostic diet may adversely impact prognosis among African-American women with high-grade serous carcinoma, and specifically among ever smokers.

Perceived discrimination, trust in physicians, and prolonged symptom duration before ovarian cancer diagnosis in the African American Cancer Epidemiology Study

Discrimination and trust are known barriers to accessing health care. Despite well-documented racial disparities in the ovarian cancer care continuum, the role of these barriers has not been examined. This study evaluated the association of everyday discrimination and trust in physicians with a prolonged interval between symptom onset and ovarian cancer diagnosis (hereafter referred to as prolonged symptom duration). Subjects included cases enrolled in the African American Cancer Epidemiology Study, a multisite case-control study of epithelial ovarian cancer among black women. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations of everyday discrimination and trust in physicians with a prolonged symptom duration (1 or more symptoms lasting longer than the median symptom-specific duration), and it controlled for access-to-care covariates and potential confounders. Among the 486 cases in this analysis, 302 women had prolonged symptom duration. In the fully adjusted model, a 1-unit increase in the frequency of everyday discrimination increased the odds of prolonged symptom duration 74% (OR, 1.74; 95% CI, 1.22-2.49), but trust in physicians was not associated with prolonged symptom duration (OR, 0.86; 95% CI, 0.66-1.11). Perceived everyday discrimination was associated with prolonged symptom duration, whereas more commonly evaluated determinants of access to care and trust in physicians were not. These results suggest that more research on the effects of interpersonal barriers affecting ovarian cancer care is warranted.

Ovarian Cancer in Women of African Ancestry (OCWAA) consortium: a resource of harmonized data from eight epidemiologic studies of African American and white women.

Although the incidence rate of epithelial ovarian cancer (EOC) is somewhat lower in African American (AA) than white women, survival is worse. The Ovarian Cancer in Women of African Ancestry (OCWAA) consortium will overcome small, study-specific sample sizes to better understand racial differences in EOC risk and outcomes. We harmonized risk factors and prognostic characteristics from eight U.S. the North Carolina Ovarian Cancer Study (NCOCS), the Los Angeles County Ovarian Cancer Study (LACOCS), the African American Cancer Epidemiology Study (AACES), the Cook County Case-Control Study (CCCCS), the Black Women's Health Study (BWHS), the Women's Health Initiative (WHI), the Multiethnic Cohort Study (MEC), and the Southern Community Cohort Study (SCCS). Determinants of disparities for risk and survival in 1,146 AA EOC cases and 2,922 AA controls will be compared to 3,368 white EOC cases and 10,270 white controls. Analyses include estimation of population-attributable risk percent (PAR%) by race. OCWAA is uniquely positioned to study the epidemiology of EOC in AA women compared with white women to address disparities. Studies of EOC have been underpowered to address factors that may explain AA-white differences in the incidence and survival. OCWAA promises to provide novel insight into disparities in ovarian cancer.

Cardiovascular comorbidities and risk of ovarian carcinoma among African American women in the African American cancer epidemiology study (AACES)

Cardiovascular comorbidities and risk of ovarian carcinoma among African American women in the African American cancer epidemiology study (AACES)

Targetable Immune Regulatory Molecule Expression in High-Grade Serous Ovarian Carcinomas in African American Women: A Study of PD-L1 and IDO in 112 Cases From the African American Cancer Epidemiology Study (AACES).

African American women with high-grade serous ovarian carcinoma have worse outcomes compared with women of European descent. Although the discrepancy is partially attributed to differences in access to care, the tumor immune microenvironment may also contribute. Expression of targetable immune regulatory molecules such as programmed cell death ligand-1 (PD-L1) and indoleamine 2,3 dioxygenase (IDO) is of particular interest as it may help guide therapy in this population. Using cases from the largest study of African American women with ovarian cancer, the African American Cancer Epidemiology Study, we characterized PD-L1 and IDO expression in 112 high-grade serous ovarian carcinomas. Immunohistochemistry for PD-L1, IDO, CD8, FOX3p, and CD68 was performed. PD-L1 and IDO were scored as the percentage of positive tumor cells and tumor-associated immune cells. CD8 and FOX3p counts were averaged across 10 high-power fields. Cox proportional hazards regression was used to evaluate the association between PD-L1 and IDO expression and survival. Tumor cells were positive for PD-L1 and IDO in 29% and 58% of cases, respectively. The majority showed <10% staining, and no cases exceeded 25% positivity. The majority of PD-L1-positive cases coexpressed IDO. PD-L1 and IDO expression was associated with higher CD8 and FOX3p counts (P<0.05). No association was observed between PD-L1 and IDO and survival. In summary, expression of PD-L1 and IDO is seen in a subset of high-grade serous ovarian carcinoma from African American women and is correlated with elevated lymphocyte infiltration. While PD-L1 and IDO co-expression suggests a role for dual immunotherapy, diffuse expression of PD-L1 and IDO is rare, invoking caution regarding the potential for immunotherapeutic response.

Individual, Social, and Societal Correlates of Health-Related Quality of Life Among African American Survivors of Ovarian Cancer: Results from the African American Cancer Epidemiology Study.

While the incidence of epithelial ovarian cancer (EOC) is lower among African American (AA) women compared with European American (EA) women, AA women have markedly worse outcomes. In this study, we describe individual, social, and societal factors in health-related quality of life (HRQL) in AA women diagnosed with EOC in the African American Cancer Epidemiology Study (AACES) that we hypothesize may influence a patient's capacity to psychosocially adjust to a diagnosis of cancer. There were 215 invasive EOC cases included in the analysis. HRQL was measured using the SF-8 component scores for physical (PCS) and mental (MCS) health. We used least squares regression to test the effects of individual dispositional factors (optimism and trait anxiety); social level (perceived social support); and societal-level factors (SES defined as low family income and low educational attainment, and perceived discrimination) on HRQL, while adjusting for patient age, tumor stage, body mass index, and comorbidity. Mediation analysis was applied to test whether social support and physical activity buffer impacts of EOC on HRQL. Optimism, trait anxiety, social support, poverty, and past perceived discrimination were significantly associated with HRQL following diagnosis of EOC. Specifically, higher family income, lower phobic anxiety, and higher social support were associated with better wellbeing on the MCS and PCS (p < 0.01). Higher perceived discrimination was associated with both lower MCS and PCS, whereas higher optimism was associated with higher MCS. Physical activity (MET-min/week) and social support displayed significant overall mediation for effects of SES on MCS and PCS, but not for trait anxiety. Both pre- and postdiagnosis characteristics of AA women with EOC are important predictors of HRQL after cancer diagnosis. Individual, social, and societal-level factors each contribute to HRQL status with EOC and should be assessed.

Benign gynecologic conditions are associated with ovarian cancer risk in African-American women: a case-control study.

The association between common benign gynecologic conditions and ovarian cancer remains under-studied in African Americans. Therefore, we examine the association between self-reported history of benign gynecologic conditions and epithelial ovarian cancer risk in African-American women. Data from a large population-based, multi-center case-control study of epithelial ovarian cancer in African-American women were analyzed to estimate the association between self-reported history of endometriosis, pelvic inflammatory disease (PID), fibroid, and ovarian cyst with epithelial ovarian cancer. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for the associations between individual and composite gynecologic conditions and ovarian cancer. 600 cases and 752 controls enrolled in the African American Cancer Epidemiology Study between 1 December 2010 and 31 December 2015 comprised the study population. After adjusting for potential confounders, a history of endometriosis was associated with ovarian cancer (OR 1.78; 95% CI 1.09-2.90). A non-significant association of similar magnitude was observed with PID (OR 1.33; 95% CI 0.82-2.16), while no association was observed in women with a history of fibroid or ovarian cyst. A positive trend was observed for an increasing number of reported gynecologic conditions (p = 0.006) with consistency across histologic subtypes and among both oral contraceptive users and non-users. A self-reported history of endometriosis among African-American women was associated with increased risk of ovarian cancer. Having multiple benign gynecologic conditions also increased ovarian cancer risk.

Abstract C42: Correlates of health-related quality of life among African-American survivors of ovarian cancer: Results from the AACES Study

Abstract Background: The incidence of epithelial ovarian cancer (EOC) is lower among African-American (AA) women compared to European American (EA) women (9.8 vs. 13.0 cases/100,000), but AA women have markedly worse outcomes. The purpose of this study is to describe the health-related quality of life (HRQL) in AA women with EOC and its correlates using data from a multisite population-based case-control study of invasive EOC in AA women, the African American Cancer Epidemiology Study (AACES). Methods: 215 cases completed a first annual follow-up questionnaire, including the HRQL and psychosocial surveys &amp;lt;18 months post diagnosis. The primary HRQL outcome was assessed with SF-8 component scores for physical (PCS) and mental (MCS) health. Correlates examined were patient, disease and treatment characteristics, modified Charlson index, perceived social support, perceived discrimination, leisure-time physical activity, the Life Orientation Test (LOTR), and phobic anxiety (Crown-Crisp Inventory, CCI-PA). Ordinary least squares regression was used to estimate linear trend effects for all predictors adjusting for age at diagnosis, comorbidity, BMI, stage and income. Results: Higher household family income, lower phobic anxiety, higher social support, and higher leisure physical activity levels were associated with higher MCS and PCS (p &amp;lt; 0.01). Higher perceived discrimination was associated with both lower MCS and PCS, while higher optimism (LOTR) was associated with higher MCS. In multivariable analyses including all predictors, CCI-PA and LOTR remained significant predictors of MCS (p &amp;lt; 0.01), and BMI, phobic anxiety, and social support predicted PCS (p &amp;lt; 0.001). Conclusion: Prediagnosis characteristics and exposures of AA women with EOC are important predictors of HRQL after cancer diagnosis, and in AACES were more important than tumor characteristics. Cancer survivorship programs that enhance patients' social support and physical activity could have important benefits by reducing emotional distress and increasing perceived vitality. Citation Format: Roger T. Anderson, Fabian Camacho, Elisa Bandera, Ellen Funkhouser, Patricia Moorman, Lisa Paddock, Lauren C. Peres, Edward Peters, Sarah E. Abbott, Anthony J. Alberg, Jill Barnholtz-Sloan, Melissa Bondy, Michele L. Cote, Ann Schwartz, Paul Terry, Joellen Schildkraut. Correlates of health-related quality of life among African-American survivors of ovarian cancer: Results from the AACES Study [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr C42.

Abstract C24: Determinants of delays in care-seeking for ovarian cancer symptoms in African American women

Abstract Introduction: Ovarian cancer is the most deadly gynecologic cancer, and the mortality burden is disproportionately higher among African American women. Women diagnosed with stage IV disease have less than a 30% 5-year survival rate, compared to 90% 5-year survival in stage I disease, which highlights the importance of early diagnosis. Lack of financial means and limited access to care may contribute to delays in symptomatic women seeking treatment, with consequent later stage at diagnosis. However, several studies, performed in samples predominantly comprised of White women, suggest insurance and income do not sufficiently reflect access to care. Here, we examine whether delay in care-seeking (captured through duration of symptoms prior to diagnosis) among African American women is more strongly influenced by socioeconomic status, access to care, or social access barriers (discrimination and trust in physicians). Methods: This analysis includes data from 550 African American women with ovarian cancer enrolled in the African American Cancer Epidemiology Study (AACES). AACES is a case-control study spanning 11 geographic regions in the United States: North Carolina, South Carolina, Georgia, Alabama, Tennessee, Louisiana, Texas, New Jersey, Ohio, Chicago, and Detroit. Included in the phone-administered AACES survey were questions about symptoms associated with ovarian cancer such as abdominal lumps, changes in bowel habits, and abnormal vaginal bleeding, in the year prior to ovarian cancer diagnosis. If a woman indicated she had a symptom, duration of the symptom was recorded in months. Logistic regression was used to estimate the odds ratios between predictors of accessing care and the outcome of treatment delay. The outcome was defined as having any of the 10 symptoms for at least eight months prior to diagnosis (i.e., those exceeding the seven-month mean symptom duration in this population). Models were adjusted for region, age at diagnosis, histotype, first-degree family history of breast or ovarian cancer, marital status, body mass index, Charlson comorbidity score, pelvic-inflammatory disease history, education, and income. Access to care variables included regular source of health care, insurance, regular physician relationship, and experiencing a barrier to accessing health care. Perceived discrimination was evaluated using the mean response score for questions from Williams' Everyday Discrimination Scale. Trust in physicians was modeled using the mean response score from the Anderson Dedrick Trust in Physicians Scale. Results: 41% (n=227) of women reported having at least one symptom for eight months prior to diagnosis. After adjustment for confounders, trust in physicians was inversely associated with longer duration of symptoms. A one-unit increase in the mean trust score was associated with 0.73 times the odds of women reporting undiagnosed symptoms in the previous 8 months (OR 0.73 CI 0.55-0.96). Conversely, a one-unit increase in frequency of mean everyday discrimination score was associated with 1.56 times the odds of 8 months of undiagnosed symptoms (OR 1.56 CI 1.14-2.15), after adjustment for confounders. Access to care measures and socioeconomic variables were not associated with longer symptom length in this study population. Conclusions: Various studies have considered access to care mainly in terms of availability of health insurance. Our results suggest perceived discrimination and lack of trust in physicians are important barriers to African American women seeking treatment for their ovarian cancer symptoms, even after controlling for socioeconomic status, insurance, and source of care. Citation Format: Megan Mullins, Michele L. Cote, Sarah Abbott, Anthony J. Alberg, Elisa V. Bandera, Jill Barnholtz-Sloan, Melissa Bondy, Fabian Camacho, Ellen Funkhouser, Patricia G. Moorman, Lauren C. Peres, Ann G. Schwartz, Paul D. Terry, Frances Wang, Joellen M. Schildkraut, Edward S. Peters. Determinants of delays in care-seeking for ovarian cancer symptoms in African American women [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr C24.

Abstract IA40: Obesity in breast and ovarian cancers: Racial/ethnic disparities

Abstract IA40: Obesity in breast and ovarian cancers: Racial/ethnic disparities

Abstract 5318: High-grade serous ovarian cancer DNA methylation and survival in African-American women

Abstract Ovarian cancer is the most lethal gynecologic cancer in the United States, and African-American (AA) women have the poorest outcomes compared to other racial/ethnic groups. Although several biomarkers have been proposed to establish prognosis in European ancestry (EA) patients, including some DNA methylation markers (FGF4, FGF21, MYLK2, MYLK3, MYL7, and ITGAE) (Phelps et al., 2017), it is unknown if these or other markers are applicable to AA patients. Using data from the African-American Cancer Epidemiology Study (AACES), we evaluated 1) if DNA methylation is associated with residual disease and survival, and 2) if previously reported CpG biomarkers for EA women are related to survival in AA women. 121 AA women with high-grade serous ovarian cancer (HGSOC) were randomly selected from 600 women enrolled in AACES. Clinical records and formalin-fixed, paraffin-embedded (FFPE) tumor tissue were retrieved, and a pathologist reviewed histopathologic slides to confirm diagnosis. 92 HGSOC had complete clinical information. DNA methylation was measured using Illlumina HumanMethylationEPIC. Beta-values were preprocessed (RELIC, Tost+BMIQ and ComBat). Low quality probes were filtered. Tumor purity was estimated using InfiniumPurify; &amp;lt;30% was considered low purity. Four cell estimates (RefFreecellmix) were used as a proxy of cell composition. To evaluate DNA methylation alterations, we used the top 100K most variable CpG sites and a semisupervised recursively partitioned mixture model (ssRPMM) approach to delineate the patients into RPMM classes. We also evaluated the six candidate CpGs from Phelps et al. The dataset was divided into training and validation subsets (50% each); if findings were consistent, a pooled statistic is reported. We used logistic regression to evaluate the association between DNA methylation and residual disease; Cox proportional hazard models were used for survival. Models were adjusted for age at diagnosis, low purity, cell types, neoadjuvant therapy, tissue source (adnexa vs. peritoneum), histology (serous vs. mixed), and residual disease. The RPMM classes were not associated with residual disease. For survival, four RPMM classes were delineated, which we collapsed into two classes. A lower risk of mortality was observed for one of the RPMM classes, HR: 0. 03[95% CI: 0.01-0.12]. This “low risk” RPMM class grouped five CpGs in genes PLEC1, AP5B1, DNAH7 and MAPK15. These genes have been associated with cell motility and ovarian cancer ascites. Among the candidate CpGs, we only observed a trend to better survival per every 10% increase in MYLK3 CpG methylation, HR: 0.51 [95%CI: 0.24-1.10]. These preliminary results suggest that some DNA methylation modifications may identify subgroups of AA women with better survival. Previously reported biomarkers in EA may not be as useful in AA women. Future studies with increased sample size may help to disentangle these associations. Citation Format: Lucas A. Salas, Lauren C. Peres, Sarah E. Abbott, Casey S. Greene, Jeffrey R. Marks, Anthony J. Alberg, Elisa V. Bandera, Jill S. Barnholtz-Sloan, Ann G. Schwartz, Michele L. Cote, Patricia G. Moorman, Ellen M. Funkhouser, Edward S. Peters, Melissa L. Bondy, Paul D. Terry, Jennifer A. Doherty, Brock C. Christensen, Joellen M. Schildkraut. High-grade serous ovarian cancer DNA methylation and survival in African-American women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5318.

Racial/ethnic differences in the epidemiology of ovarian cancer: a pooled analysis of 12 case-control studies.

Ovarian cancer incidence differs substantially by race/ethnicity, but the reasons for this are not well understood. Data were pooled from the African American Cancer Epidemiology Study (AACES) and 11 case-control studies in the Ovarian Cancer Association Consortium (OCAC) to examine racial/ethnic differences in epidemiological characteristics with suspected involvement in epithelial ovarian cancer (EOC) aetiology. We used multivariable logistic regression to estimate associations for 17 reproductive, hormonal and lifestyle characteristics and EOC risk by race/ethnicity among 10 924 women with invasive EOC (8918 Non-Hispanic Whites, 433 Hispanics, 911 Blacks, 662 Asian/Pacific Islanders) and 16 150 controls (13 619 Non-Hispanic Whites, 533 Hispanics, 1233 Blacks, 765 Asian/Pacific Islanders). Likelihood ratio tests were used to evaluate heterogeneity in the risk factor associations by race/ethnicity. We observed statistically significant racial/ethnic heterogeneity for hysterectomy and EOC risk (P = 0.008), where the largest odds ratio (OR) was observed in Black women [OR = 1.64, 95% confidence interval (CI) = 1.34-2.02] compared with other racial/ethnic groups. Although not statistically significant, the associations for parity, first-degree family history of ovarian or breast cancer, and endometriosis varied by race/ethnicity. Asian/Pacific Islanders had the greatest magnitude of association for parity (≥3 births: OR = 0.38, 95% CI = 0.28-0.54), and Black women had the largest ORs for family history (OR = 1.77, 95% CI = 1.42-2.21) and endometriosis (OR = 2.42, 95% CI = 1.65-3.55). Although racial/ethnic heterogeneity was observed for hysterectomy, our findings support the validity of EOC risk factors across all racial/ethnic groups, and further suggest that any racial/ethnic population with a higher prevalence of a modifiable risk factor should be targeted to disseminate information about prevention.

Tubal ligation and ovarian cancer risk in African American women.

Tubal ligation has been associated with reduced risk of epithelial ovarian cancer (EOC) in studies of primarily white women, but less is known about the association in African American (AA) women. We sought to evaluate the associations among 597 invasive ovarian cancer cases and 742 controls of AA descent recruited from the African American Cancer Epidemiology Study, a population-based case-control study in 11 geographical areas in the US. Multivariable logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for potentially confounding factors. An inverse association between tubal ligation and EOC was observed that was not statistically significant (OR 0.88, 95% CI 0.68-1.14). However, an inverse association with EOC risk was observed among women who had a tubal ligation at age 35years or older (OR 0.64; 95% CI 0.41-0.98), but not among those who had a tubal ligation before age 35 (OR 0.98; 95% CI 0.74-1.29) (p for interaction=0.08). The association also varied considerably by tumor subtype. A strong inverse association was observed for endometrioid tumors (OR 0.31, 95% CI 0.14-0.70), whereas associations with mucinous (OR 0.87, 95% CI 0.36-2.12) and serous (OR 0.94, 95% CI 0.71-1.24) tumors were weaker and not statistically significant. A statistically non-significant positive association for clear cell tumors (OR 1.84, 95% CI 0.58-5.82) was based on a low number of cases. Our findings show that tubal ligation may confer a reduced risk for EOC among AA women that is comparable to the associations that have been previously observed in primarily white populations.

Abstract 1289: Evaluation of vitamin D receptor regulated genes reveals EGFR polymorphism is associated with high-grade serous ovarian cancer in African American women

Abstract Few studies have evaluated genetic risk factors for ovarian cancer in African American women. In a previous study with small sample sizes, Vitamin D Receptor (VDR) variants were shown to increase risk of epithelial ovarian cancer (EOC) in that population. This study sought to replicate those findings and assess gene variants from the VDR regulatory pathway. We assessed SNPs (genotyped+imputed) from 5 gene regions which included VDR and genes regulated by VDR, including UGT1A, UGT2B, CYP3A4/5 and EGFR in 755 EOC cases and 1,235 controls among women of African ancestry from the Ovarian Cancer Association Consortium (OCAC). We also performed analyses restricted to 537 patients with HGSOC represented in the overall analysis of EOC. SNPs were genotyped using the custom-designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set for genotyped and imputed SNPs evaluated at the 5 gene regions (918 SNPs in UGT1A, 6302 SNPs in UGT2B, 410 SNPs in CYP3A4/5, and 824 SNPs in EGFR). Logistic regression was performed using an additive 1 degree of freedom model for genetic inheritance with adjustment for two principal components of ancestry to estimate odds ratios (OR) and 95 % confidence intervals (CI). For each gene region, we applied a gene-specific Bonferroni-threshold for statistical significance defined as 0.05 / number of SNPs examined for that gene. Based on this significance threshold, a statistically significant association with HGSOC was identified in the EGFR region for the imputed SNP, rs114972508 (per allele OR = 2.32, 95% CI = 1.58, 3.40 p=1.6e-05, imputation R-squared=0.89). We further identified suggestive associations (P &amp;lt; 1.0e-06) with EOC for 10 imputed SNPs located within the UGT2B4 gene. We did not replicate previous associations in the 282 SNPs examined in the VDR gene for EOC overall or among HGSOC. In summary, we identified statistically significant association for variants from the EGFR region, and suggestive evidence of association for variants within the UGT2B region in genetic association analyses of ovarian cancer in women of African Ancestry. Data from in vitro experiments suggest that EGFR transcription and proliferative function is suppressed via VDR binding. Thus EGFR association with HGSOC may be a marker of VDR activity. UGT2B4 variants have not been previously explored in ovarian cancer but shown to be nominally associated with breast cancer in women of African ancestry. UGT2B4 enzymes, part of the phase II liver detoxification pathway, are important in the clearance of steroid hormones, bile acid and drug metabolism. Alterations in EGFR and UGT2B4 could perturb enzyme efficacy and proliferation in ovaries and impact susceptibility to ovarian cancer. Future studies will be needed to validate the associations of the imputed SNPs and to determine the impact of EGFR and UGT variants on cancer development. Citation Format: Delores J. Grant, Ani Manichaikul, Lauren C. Peres, Xin-Qun Wang, Ann G. Schwartz, Anna Wu, Edward Peters, Patricia Moorman, Michele L. Cote, Melissa Bondy, Linda E. Kelemen, Jill Barnholtz-Sloan, Temitope O. Keku, Cathrine Hoyo, Andrew Berchuck, Paul Pharoah, Joellen M. Schildkraut, African American Cancer Epidemiology Study (AACES) and the Ovarian Cancer Assoc Consortium (OCAC). Evaluation of vitamin D receptor regulated genes reveals EGFR polymorphism is associated with high-grade serous ovarian cancer in African American women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1289. doi:10.1158/1538-7445.AM2017-1289

Dietary Quality and Ovarian Cancer Risk in African-American Women.

This study evaluated 3 index-based dietary patterns-Healthy Eating Index (HEI)-2005, HEI-2010, and Alternate Healthy Eating Index (AHEI)-2010-in relation to ovarian cancer risk in African-American women. The study was conducted among 415 ovarian cancer cases and 629 age- and site-matched controls of African-American descent recruited from the population-based African American Cancer Epidemiology Study. Multivariable unconditional logistic regression models were used to estimate odds ratios and 95% confidence intervals between quartiles of dietary quality indices and ovarian cancer risk, adjusting for potential confounders. We found that higher AHEI-2010 scores, but not HEI-2005 or HEI-2010 scores, were associated with lower risk of ovarian cancer (comparing the highest quartile (4th) vs. lowest (1st), odds ratio (OR)=0.66, 95% confidence interval (CI): 0.45, 0.98; P for trend=0.05). When stratified by menopausal status, no noteworthy associations were observed among premenopausal women. However, among postmenopausal women, greater adherence to HEI-2010 (quartile 4 vs. quartile 1, OR=0.57, 95% CI: 0.36, 0.92; P for trend=0.03) and AHEI-2010 (quartile 4 vs. quartile 1, OR=0.49, 95% CI: 0.31, 0.78; P for trend=0.01) were inversely associated with ovarian cancer. Our findings indicate that adherence to an overall healthy dietary pattern may reduce ovarian cancer risk in African-American women, and particularly among postmenopausal African-American women.

Cigarette smoking and the association with serous ovarian cancer in African American women: African American Cancer Epidemiology Study (AACES)

Smoking is a risk factor for mucinous ovarian cancer (OvCa) in Caucasians. Whether a similar association exists in African Americans (AA) is unknown. We conducted a population-based case-control study of incident OvCa in AA women across 11 geographic locations in the US. A structured telephone interview asked about smoking, demographic, health, and lifestyle factors. Odds ratios and 95% confidence intervals (OR, 95% CI) were estimated from 613 cases and 752 controls using unconditional logistic regression in multivariable adjusted models. Associations were greater in magnitude for serous OvCa than for all OvCa combined. Compared to never smokers, increased risk for serous OvCa was observed for lifetime ever smokers (1.46, 1.11-1.92), former smokers who quit within 0-2years of diagnosis (5.48, 3.04-9.86), and for total pack-years smoked among lifetime ever smokers (0-5 pack-years: 1.79, 1.23-2.59; >5-20 pack-years: 1.52, 1.05-2.18; >20 pack-years: 0.98, 0.61-1.56); however, we observed no dose-response relationship with increasing duration or consumption and no significant associations among current smokers. Smoking was not significantly associated with mucinous OvCa. Associations for all OvCa combined were consistently elevated among former smokers. The proportion of ever smokers who quit within 0-2years was greater among cases (23%) than controls (7%). Cigarette smoking may be associated with serous OvCa among AA, which differs from associations reported among Caucasians. Exposure misclassification or reverse causality may partially explain the absence of increased risk among current smokers and lack of dose-response associations. Better characterization of smoking patterns is needed in this understudied population.

Ovarian Cancer Risk Associated With Benign Gynecologic Conditions in African American Women [13J

INTRODUCTION: The association between common benign gynecologic conditions and ovarian cancer remains under-studied in African Americans (AA). Therefore, we examined the association between self-reported history of benign gynecologic conditions and epithelial ovarian cancer risk in AA women. METHODS: Data from a large population-based, multi-center case-control study of epithelial ovarian cancer in AA women were analyzed to estimate the association between self-reported history of endometriosis, fibroid, pelvic inflammatory disease (PID), and ovarian cyst with epithelial ovarian cancer. Logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for the associations between individual and composite gynecologic conditions and ovarian cancer. RESULTS: 628 cases and 752 controls enrolled in the African American Cancer Epidemiology Study between December 1, 2010 and December 31, 2015 were included in the analysis. After adjusting for potential confounders, a history of endometriosis was associated with ovarian cancer (OR 1.73; 95% CI 1.06-2.81). A modest association was observed with PID (OR 1.57; 95% CI 0.98-2.51), while no association was observed in women with a history of fibroid or ovarian cyst. A positive trend was observed for an increasing number of reported gynecologic conditions (p=0.002) with consistency across histologic subtypes and among both oral contraceptive users and non-users. CONCLUSION: A self-reported history of endometriosis among AA women was associated with increased risk of ovarian cancer. Having multiple benign gynecologic conditions had a cumulative effect on ovarian cancer risk.

Premenopausal Hysterectomy and Risk of Ovarian Cancer in African-American Women.

Although the inverse association between hysterectomy and epithelial ovarian cancer (EOC) was considered well established, investigators in recent studies including women diagnosed after 2000 have observed modest increases in risk. Most studies have been conducted in white women with little representation of African-American women. We examined the relationship between premenopausal hysterectomy and EOC in African-American women and explored whether hormone therapy (HT) modified this association in 614 cases and 743 controls enrolled in the African American Cancer Epidemiology Study (2010-2015). Premenopausal hysterectomy was inversely associated with the odds of EOC (odds ratio (OR)=0.75, 95% confidence interval (CI): 0.56, 1.01). Qualitative interaction by estrogen-only HT was present; among never users of estrogen-only HT, premenopausal hysterectomy was associated with a significantly decreased odds of EOC (OR=0.65, 95% CI: 0.46, 0.92), whereas among users of estrogen-only HT, a positive association was observed (OR=1.71, 95% CI: 0.76, 3.84). In a population of African-American women diagnosed after 2000, our overall results are consistent with the inverse association observed in the era before 2000, yet the effect modification by HT suggests that HT use among women who have had hysterectomies may negate the protective effects of hysterectomy on EOC, creating the appearance of a null or slightly increased risk.

Supplemental Selenium May Decrease Ovarian Cancer Risk in African-American Women

BackgroundTo our knowledge, no previous study has evaluated the associations of antioxidant intake with the risk of ovarian cancer in African-American women, who are known to have high mortality from the disease. ObjectiveWe sought to evaluate these associations among 406 ovarian cancer cases and 632 age- and site-matched controls of African-American descent recruited from AACES (African American Cancer Epidemiology Study), a population-based, case-control study in 11 geographical areas within the United States. MethodsMultivariable logistic regression models were used to estimate ORs and 95% CIs adjusted for a wide range of potentially confounding factors, including age, region, education, parity, oral contraceptive use, menopause, tubal ligation, family history, body mass index (BMI), smoking status, total energy, and physical activity. ResultsWomen with the highest intakes of supplemental selenium (>20 μg/d) had an ∼30% lower risk of ovarian cancer than those with no supplemental intake (OR: 0.67; 95% CI: 0.46, 0.97; P-trend = 0.035). This inverse association was stronger in current smokers (OR: 0.13; 95% CI: 0.04, 0.46; P-trend = 0.001). There was no association with dietary selenium. The associations with carotenoid intakes were weak and nonsignificant (P = 0.07–0.60). We observed no association with dietary or supplemental intake of vitamin C or vitamin E. There were no appreciable differences in results between serous and nonserous tumors. ConclusionsThese findings provide the first insights, to our knowledge, into the potential association between antioxidants and ovarian cancer in African-American women, indicating potential inverse associations with supplemental selenium.

Lifetime number of ovulatory cycles and epithelial ovarian cancer risk in African American women.

Incessant ovulation has been consistently linked to epithelial ovarian cancer (EOC). Although reproductive characteristics differ substantially by race, the association between incessant ovulation and EOC has been evaluated only in populations of predominantly white women. In the present study, we examined the association between lifetime number of ovulatory cycles (LOCs) and EOC risk among African American (AA) women. We used data from 534 cases and 722 controls enrolled in the African American Cancer Epidemiology Study. LOCs were determined using the standard method, with modifications to include episodes of irregular or missed periods. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between LOCs and EOC risk overall and by age, while adjusting for appropriate confounders. The mean number of LOCs was 378.2 ± 105.8 for cases and 346.4 ± 117.3 for controls. Women in the highest tertile of LOCs had 59% higher odds of EOC compared to women in the lowest tertile (OR = 1.59; 95% CI = 1.15-2.20). When examining this relationship by age, the positive association with EOC was stronger among women <50years of age (OR for highest vs. lowest tertile = 2.61; 95% CI = 1.15-5.94), followed by women aged 50-60years (OR = 2.27; 95% CI = 1.30-3.94). Yet, no association was present among women aged >60years (OR = 0.79; 95% CI = 0.45-1.40). In a population of AA women, we observed a positive association between LOCs and EOC risk, providing further support for the hypothesis that incessant ovulation contributes to the etiology of EOC.