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1.
Gynecol Oncol ; 184: 31-42, 2024 May.
Article in English | MEDLINE | ID: mdl-38277919

ABSTRACT

OBJECTIVE: This study investigated the risk of an aggressive endometrial cancer (EC) diagnosis by race, ethnicity, and country of origin to further elucidate histologic disparities in non-Hispanic Black (NHB), Hispanic, Asian/Pacific Islander (API), American Indian/Alaskan Native (AIAN) vs. non-Hispanic White (NHW) patients, particularly in Hispanic or API subgroups. METHODS: Patient diagnosed between 2004 and 2020 with low grade (LG)-endometrioid endometrial cancer (ECC) or an aggressive EC including grade 3 EEC, serous carcinoma, clear cell carcinoma, mixed epithelial carcinoma, or carcinosarcoma in the National Cancer Database were studied. The odds ratio (OR) and 95% confidence interval (CI) for diagnosis of an aggressive EC histology was estimated using logistic modeling. RESULTS: There were 343,868 NHW, 48,897 NHB, 30,013 Hispanic, 15,015 API and 1646 AIAN patients. The OR (95% CI) for an aggressive EC diagnosis was 3.07 (3.01-3.13) for NHB, 1.08 (1.06-1.11) for Hispanic, 1.17 (1.13-1.21) for API and 1.07 (0.96-1.19) for AIAN, relative to NHW patients. Subset analyses by country of origin illustrated the diversity in the OR for an aggressive EC diagnosis among Hispanic (1.18 for Mexican to 1.87 for Dominican), Asian (1.14 Asian Indian-Pakistani to 1.48 Korean) and Pacific Islander (1.00 for Hawaiian to 1.33 for Samoan) descendants. Hispanic, API and AIAN patients were diagnosed 5-years younger that NHW patients, and the risk for an aggressive EC histology were all significantly higher than NHW patients after correcting for age. Insurance status was another independent risk factor for aggressive histology. CONCLUSIONS: Risk of an aggressive EC diagnosis varied by race, ethnicity, and country of origin. NHB patients had the highest risk, followed by Dominican, South/Central American, Cuban, Korean, Thai, Vietnamese, and Filipino descendants.


Subject(s)
Endometrial Neoplasms , Humans , Female , Endometrial Neoplasms/ethnology , Endometrial Neoplasms/pathology , Middle Aged , Aged , United States/epidemiology , Adult , White People/statistics & numerical data , Hispanic or Latino/statistics & numerical data , Adenocarcinoma, Clear Cell/pathology , Adenocarcinoma, Clear Cell/ethnology , Adenocarcinoma, Clear Cell/epidemiology , Carcinosarcoma/pathology , Carcinosarcoma/ethnology , Native Hawaiian or Other Pacific Islander/statistics & numerical data , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/ethnology , Aged, 80 and over , Ethnicity/statistics & numerical data , Health Status Disparities , Cystadenocarcinoma, Serous/pathology , Cystadenocarcinoma, Serous/ethnology , Black or African American/statistics & numerical data
2.
Cancer Epidemiol Biomarkers Prev ; 31(1): 132-141, 2022 01.
Article in English | MEDLINE | ID: mdl-34697060

ABSTRACT

BACKGROUND: Ovarian clear cell carcinoma (OCCC) is a rare ovarian cancer histotype that tends to be resistant to standard platinum-based chemotherapeutics. We sought to better understand the role of DNA methylation in clinical and biological subclassification of OCCC. METHODS: We interrogated genome-wide methylation using DNA from fresh frozen tumors from 271 cases, applied nonsmooth nonnegative matrix factorization (nsNMF) clustering, and evaluated clinical associations and biological pathways. RESULTS: Two approximately equally sized clusters that associated with several clinical features were identified. Compared with Cluster 2 (N = 137), Cluster 1 cases (N = 134) presented at a more advanced stage, were less likely to be of Asian ancestry, and tended to have poorer outcomes including macroscopic residual disease following primary debulking surgery (P < 0.10). Subset analyses of targeted tumor sequencing and IHC data revealed that Cluster 1 tumors showed TP53 mutation and abnormal p53 expression, and Cluster 2 tumors showed aneuploidy and ARID1A/PIK3CA mutation (P < 0.05). Cluster-defining CpGs included 1,388 CpGs residing within 200 bp of the transcription start sites of 977 genes; 38% of these genes (N = 369 genes) were differentially expressed across cluster in transcriptomic subset analysis (P < 10-4). Differentially expressed genes were enriched for six immune-related pathways, including IFNα and IFNγ responses (P < 10-6). CONCLUSIONS: DNA methylation clusters in OCCC correlate with disease features and gene expression patterns among immune pathways. IMPACT: This work serves as a foundation for integrative analyses that better understand the complex biology of OCCC in an effort to improve potential for development of targeted therapeutics.


Subject(s)
Adenocarcinoma, Clear Cell/genetics , DNA Methylation , Ovarian Neoplasms/genetics , Adenocarcinoma, Clear Cell/ethnology , Adenocarcinoma, Clear Cell/pathology , Adult , Aged , Aged, 80 and over , Aneuploidy , Class I Phosphatidylinositol 3-Kinases/genetics , CpG Islands/genetics , DNA-Binding Proteins/genetics , Disease Progression , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Middle Aged , Mutation , Neoplasm Staging , Ovarian Neoplasms/ethnology , Ovarian Neoplasms/pathology , Prognosis , Transcription Factors/genetics , Tumor Suppressor Protein p53/genetics
3.
J Pathol ; 255(3): 285-295, 2021 11.
Article in English | MEDLINE | ID: mdl-34322886

ABSTRACT

Little is known about the immune environment of ovarian clear cell carcinoma (OCCC) and its impact on various ethnic backgrounds. The aim of this OCCC immune-related gene expression signatures (irGES) study was to address the interaction between tumour and immune environment of ethnically-diverse Asian and Caucasian populations and to identify relevant molecular subsets of biological and clinical importance. Our study included 264 women from three different countries (Singapore, Japan, and the UK) and identified four novel immune subtypes (PD1-high, CTLA4-high, antigen-presentation, and pro-angiogenic subtype) with differentially expressed pathways, and gene ontologies using the NanoString nCounter PanCancer Immune Profiling Panel. The PD1-high and CTLA4-high subtypes demonstrated significantly higher PD1, PDL1, and CTLA4 expression, and were associated with poorer clinical outcomes. Mismatch repair (MMR) protein expression, assessed by immunohistochemistry, revealed that about 5% of OCCCs had deficient MMR expression. The prevalence was similar across the three countries and appeared to cluster in the CTLA4-high subtype. Our results suggest that OCCC from women of Asian and Caucasian descent shares significant clinical and molecular similarities. To our knowledge, our study is the first study to include both Asian and Caucasian women with OCCC and helps to shine light on the impact of ethnic differences on the immune microenvironment of OCCC. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.


Subject(s)
Adenocarcinoma, Clear Cell/ethnology , Adenocarcinoma, Clear Cell/immunology , Ovarian Neoplasms/ethnology , Ovarian Neoplasms/immunology , Aged , Asian People , Female , Humans , Middle Aged , Transcriptome , Tumor Microenvironment/immunology , White People
4.
Gynecol Oncol ; 157(1): 62-66, 2020 04.
Article in English | MEDLINE | ID: mdl-32008796

ABSTRACT

OBJECTIVE: To determine incidence of ovarian clear cell cancer (OCCC) by race ethnicity and how that relationship is affected by birthplace among Asian Pacific Islanders (API). METHODS: The 18 registries of the U.S. Surveillance, Epidemiology, and End Results (SEER) dataset were queried to identify all women registered with epithelial ovarian cancer from 1973 to 2013. Relative risks of OCCC to non-OCCC based on ethnicity and birthplace were compared. RESULTS: We identified 72, 501 women with epithelial ovarian cancer in the dataset; of these, 5078 (7.0%) had OCCC and 4859 (6.7%) were API. The age-adjusted incidence rate/100,000 women of OCCC was significantly higher in API women (0.6, 0.5-0.6 95% CI) compared to any other ethnicity. A significantly higher proportion of API women had OCCC (14.5%) compared to their White (6.6%, RR 2.2, p < 0.0001) and Black counterparts (4.3%, RR 3.4, p < 0.0001). The majority of API women were foreign-born (70.8%). The relative risk of clear cell compared to non-clear cell epithelial ovarian cancer was not demonstrably different among foreign born API women with ovarian cancer (RR 1.1, 95% CI 0.9 to 1.3, p = 0.6). CONCLUSIONS: We have demonstrated that, in the US, there is an elevated risk of OCCC associated with API ethnicity. Place of birth does not appear to significantly modify the association, suggesting that the increased risk of OCCC in API women may not be affected by acculturation or environmental exposure. Future research exploring the complex relationships between ethnicity and risk of malignancy will be important as we make progress in understanding disease process and treatment.


Subject(s)
Adenocarcinoma, Clear Cell/epidemiology , Native Hawaiian or Other Pacific Islander/statistics & numerical data , Ovarian Neoplasms/epidemiology , Adenocarcinoma, Clear Cell/ethnology , Aged , Carcinoma, Ovarian Epithelial/epidemiology , Carcinoma, Ovarian Epithelial/ethnology , Cohort Studies , Female , Humans , Middle Aged , Native Hawaiian or Other Pacific Islander/ethnology , Ovarian Neoplasms/ethnology , Retrospective Studies , Risk , SEER Program , United States/epidemiology
5.
Obstet Gynecol ; 134(1): 17-29, 2019 07.
Article in English | MEDLINE | ID: mdl-31188310

ABSTRACT

OBJECTIVE: To compare the outcomes of women with stage III uterine cancer treated with chemotherapy alone, external beam radiation alone, and combination chemotherapy and radiation. METHODS: The National Cancer Database was used to identify women with stage III endometrioid, serous, and clear cell uterine cancer treated with either chemotherapy (with or without vaginal brachytherapy) alone, external beam radiation (with or without brachytherapy), or combination chemotherapy and external beam radiation (with or without vaginal brachytherapy) from 2004 to 2015. Survival was estimated using Cox proportional hazards models and adjusted survival curves after propensity score analysis using inverse probability of treatment weighting to balance the clinical and demographic characteristics between the cohorts. RESULTS: Of the 20,873 patients identified, 9,456 (45.3%) received chemotherapy alone, 2,417 (11.6%) were treated with radiation alone, and 9,000 (43.1%) received chemotherapy in combination with external beam radiation. Use of combination therapy was 33.0% in 2004, and then rose to 50.5% in 2015. The mortality of the cohort was 33.1% and median survival was 115 months. Within the cohort, combination therapy was associated with a 23% reduction in mortality (hazard ratio [HR]=0.77; 95% CI 0.73-0.80) compared with chemotherapy alone. Similar findings of decreased mortality were noted in subgroup analyses for both stage IIIA (HR=0.81; 95% CI 0.68-0.98) and stage IIIC (HR=0.79; 95% CI 0.75-0.84) tumors. Similarly, when compared with radiation alone, combination therapy was accompanied by a 19% decrease in mortality (HR=0.81; 95% CI 0.73-0.89). Combination chemoradiation was associated with decreased mortality across all of the histologic subtypes. CONCLUSION: Among women with stage III uterine cancer, combination chemotherapy and external beam radiation is associated with decreased mortality compared with chemotherapy or radiation alone.


Subject(s)
Uterine Neoplasms/therapy , Adenocarcinoma, Clear Cell/ethnology , Adenocarcinoma, Clear Cell/mortality , Adenocarcinoma, Clear Cell/pathology , Adenocarcinoma, Clear Cell/therapy , Aged , Aged, 80 and over , Carcinoma, Endometrioid/ethnology , Carcinoma, Endometrioid/mortality , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/therapy , Chemotherapy, Adjuvant , Combined Modality Therapy , Cystadenocarcinoma, Serous/ethnology , Cystadenocarcinoma, Serous/mortality , Cystadenocarcinoma, Serous/pathology , Cystadenocarcinoma, Serous/therapy , Databases, Factual , Female , Humans , Hysterectomy , Middle Aged , Neoplasm Staging , Proportional Hazards Models , Radiotherapy, Adjuvant , Survival Analysis , United States , Uterine Neoplasms/ethnology , Uterine Neoplasms/mortality , Uterine Neoplasms/pathology
6.
Am J Obstet Gynecol ; 221(4): 318.e1-318.e9, 2019 10.
Article in English | MEDLINE | ID: mdl-31125544

ABSTRACT

BACKGROUND: Commonly reported incidence rates for endometrial cancer fail to take into account both the large number of hysterectomies performed each year and the dynamic change in hysterectomy rate over the past decade. Large racial differences in premenopausal hysterectomy rates between Black and White women in the United States likely affect calculation of race-based risk. OBJECTIVES: The objectives of the study were to determine how the long-term trends in Black-White differences in endometrial cancer incidence and histology type have changed over time for women at risk. STUDY DESIGN: Using longitudinal Surveillance, Epidemiology, and End Results data from 1997 to 2014 and state-level hysterectomy prevalence from the Behavioral Risk Factor Surveillance System, we calculated hysterectomy-adjusted incidence rates of endometrial cancer and the proportion of high vs low-risk endometrial cancer, by race, over time. RESULTS: In women older than 50 years who have not had a hysterectomy, endometrial cancer incidence is 87 per 100,000 from 1997 to 2014. Among White women endometrial cancer incidence changed from 102 (1997-2001) to 86 (2012-2014) cases per 100,000, with a nonsignificant decreasing linear trend (adjusted risk ratio, 0.95; 95% confidence interval, 0.91-1.00; p=0.05). In contrast, incidence for Black women was 88 (1997-2001), 101 (2002-2006), 100 (2007-2011), and 102 (2012-2014) cases per 100,000 with no decreasing trend (adjusted risk ratio, 1.02; 95% confidence interval, 0.96-1.10, P = .449). High-risk histology increased among both groups (White: adjusted risk ratio, 1.06; 95% confidence interval, 1.01-1.11; P = .015; Black: adjusted risk ratio, 1.06; 95% confidence interval, 1.02-1.10, P = .007). Racial difference in the proportion of high-risk disease remained stable. CONCLUSION: Updated hysterectomy-adjusted incidence demonstrates that endometrial cancer is the second most common cancer among women older than 50 years with a uterus and that endometrial cancer has been more common among Black women compared with White women in the United States since 2002. A clinical approach of proactive communication and routine screening for early symptoms in the perimenopausal and menopausal years, especially among Black women, is warranted. These findings can also inform equitable distribution of research funding for endometrial cancer and serve to promote public awareness of this common cancer.


Subject(s)
Adenocarcinoma, Clear Cell/epidemiology , Carcinoma, Endometrioid/epidemiology , Carcinosarcoma/epidemiology , Endometrial Neoplasms/epidemiology , Hysterectomy/statistics & numerical data , Neoplasms, Cystic, Mucinous, and Serous/epidemiology , Adenocarcinoma, Clear Cell/ethnology , Adenocarcinoma, Clear Cell/pathology , Black or African American/statistics & numerical data , Aged , Aged, 80 and over , Carcinoma, Endometrioid/ethnology , Carcinoma, Endometrioid/pathology , Carcinosarcoma/ethnology , Carcinosarcoma/pathology , Endometrial Neoplasms/ethnology , Endometrial Neoplasms/pathology , Female , Healthcare Disparities/ethnology , Humans , Incidence , Middle Aged , Neoplasms, Cystic, Mucinous, and Serous/ethnology , Neoplasms, Cystic, Mucinous, and Serous/pathology , Prevalence , SEER Program , United States/epidemiology , White People/statistics & numerical data
7.
Gynecol Oncol ; 153(3): 589-596, 2019 06.
Article in English | MEDLINE | ID: mdl-30905436

ABSTRACT

OBJECTIVE: To examine the trends of epithelial ovarian cancer histologic subtypes in Japan. METHODS: A nationwide retrospective registry study was performed between 2002 and 2015 (Japan cohort, n = 48,640). Trends were also examined in The Surveillance, Epidemiology, and End Results Program (US cohort, n = 49,936). Time-specific proportional changes of four major histological subtypes (serous, clear cell, endometrioid, and mucinous) were examined. RESULTS: The Japan cohort had more stage I disease (44.1% versus 24.9%) and less stage IV disease (10.0% versus 23.1%) than the US cohort (P < 0.001). The Japan cohort had more non-serous histology, particularly clear cell carcinoma (26.9% versus 8.4%), than the US cohort (P < 0.001). In the Japan cohort, proportion of clear cell carcinoma increased significantly from 23.4% to 29.1% between 2002 and 2010 (P < 0.001). Among stage I disease, clear cell carcinoma increased significantly in the Japan cohort from 32.9% to 40.3% between 2002 and 2015 (P < 0.001), whereas mucinous carcinoma increased significantly in the US cohort from 15.0% to 24.8% (P = 0.01). In 2015, clear cell carcinoma was most common among women aged <50 years from the Japan cohort (30.2%) versus serous carcinoma in the US cohort (50.8%). In the Japan cohort, the peak age was 75 years for serous, 57 for clear cell, and 45 for endometrioid carcinoma (P < 0.001). Mucinous carcinoma decreased until 43 years and increased again after age 73 years (P < 0.001). CONCLUSION: Characteristics of epithelial ovarian cancer in Japan are largely different compared to the US. In Japan, clear cell carcinoma has increased significantly in recent years to account for nearly 30% of epithelial ovarian cancer.


Subject(s)
Adenocarcinoma, Clear Cell/epidemiology , Carcinoma, Ovarian Epithelial/epidemiology , Neoplasms, Cystic, Mucinous, and Serous/epidemiology , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/pathology , Adenocarcinoma, Clear Cell/ethnology , Adenocarcinoma, Clear Cell/pathology , Adult , Age Distribution , Aged , Antineoplastic Agents/therapeutic use , Carcinoma, Ovarian Epithelial/ethnology , Carcinoma, Ovarian Epithelial/pathology , Female , Humans , Incidence , Japan/epidemiology , Middle Aged , Neoplasm Staging , Neoplasms, Cystic, Mucinous, and Serous/ethnology , Neoplasms, Cystic, Mucinous, and Serous/pathology , Ovarian Neoplasms/ethnology , Retrospective Studies , SEER Program , United States/epidemiology
8.
Cancer Epidemiol ; 52: 134-141, 2018 02.
Article in English | MEDLINE | ID: mdl-29306788

ABSTRACT

BACKGROUND: Over the past half century the proportion of Hispanics in the US population has been steadily increasing, and groups of Hispanic origin have diversified. Despite notable racial and ethnic disparities in ovarian cancer (OC) mortality, population-based studies on OC among Hispanic females are lacking. OBJECTIVES: To examine sub-ethnic disparities in OC mortality and survival trends using the Surveillance, Epidemiology, and End Results Program (SEER) 18 data on Hispanic women diagnosed with epithelial OC during 1992-2013. METHODS: The disparities in OC 5 year survival and mortality were examined using log-rank tests and Cox proportional hazards models, adjusted for sociodemographic and pathological characteristics, time of diagnosis, receipt of resection surgery and county socioeconomic status. Trends in 5-year survival rates were examined using joinpoint regression models. RESULTS: The 5-year survival was lowest in Puerto Ricans (median survival: 33 months; survival rate: 31.07%) and was highest in the "Other" Hispanic subgroup (median survival: 59 months; survival rate: 49.14%) (log-rank test: P < 0.001). The OC-specific death hazards in Mexicans (HRadj: 0.82, 95%CI: 0.67-1.00, P = 0.048), South or Central Americans (HRadj: 0.77, 95%CI: 0.62-0.96, P = 0.005) and Other Hispanics (HRadj: 0.76, 95%CI: 0.63-0.92, P = 0.038) were significantly lower than for Puerto Ricans. Mortality rates of Cubans and Puerto Ricans were not significantly different. During 1992-2008, there were non-significant increasing trends in the 5-year all-cause and OC-specific survival rates: from 43.37% to 48.94% (APC = 0.41, P = 0.40) and from 48.72% to 53.46% (APC = 0.29, P = 0.50), respectively. CONCLUSIONS: OC mortality in Hispanic patients varied by sub-ethnicity. This heterogeneity should be considered in future cancer data collection, reports and research.


Subject(s)
Adenocarcinoma, Clear Cell/mortality , Adenocarcinoma, Mucinous/mortality , Cystadenocarcinoma, Serous/mortality , Endometrial Neoplasms/mortality , Healthcare Disparities/ethnology , Hispanic or Latino/statistics & numerical data , Ovarian Neoplasms/mortality , Adenocarcinoma, Clear Cell/ethnology , Adenocarcinoma, Mucinous/ethnology , Adolescent , Adult , Aged , Cross-Sectional Studies , Cystadenocarcinoma, Serous/ethnology , Endometrial Neoplasms/ethnology , Female , Humans , Male , Middle Aged , Ovarian Neoplasms/ethnology , SEER Program , Social Class , Survival Rate , Time Factors , United States , Young Adult
9.
Gynecol Oncol ; 148(2): 375-382, 2018 02.
Article in English | MEDLINE | ID: mdl-29233531

ABSTRACT

OBJECTIVE: To analyze whole exome sequencing (WES) data on ovarian clear cell carcinoma (OCCC) in Korean patients via the technique of next generation sequencing (NGS). Genomic profiles were compared between endometriosis-associated OCCC (EMS-OCCC) and Non-EMS-OCCC. METHODS: We used serum samples and cancer tissues, stored at the Seoul National University Hospital Human Biobank, that were initially collected from women diagnosed with OCCC between 2012 and 2016. In total, 15 patients were enrolled: 5 with pathologically confirmed EMS-OCCC and 10 with Non-EMS-OCCC. We performed NGS WES on 15 fresh frozen OCCC tissues and matched serum samples, enabling comprehensive genomic characterization of OCCC. RESULTS: OCCC was characterized by complex genomic alterations, with a median of 178 exonic mutations (range, 111-25,798) and a median of 343 somatic copy number variations (range, 43-1,820) per tumor sample. In all, 54 somatic mutations were discovered across 14 genes, including PIK3CA (40%), ARID1A (40%), and KRAS (20%) in the 15 Korean OCCCs. Copy number gains in NTRK1 (33%), MYC (40%), and GNAS (47%) and copy number losses in TET2 (73%), TSC1 (67%), BRCA2 (60%), and SMAD4 (47%) were frequent. The significantly altered pathways were associated with proliferation and survival (including the PI3K/AKT, TP53, and ERBB2 pathways) in 87% of OCCCs and with chromatin remodeling in 47% of OCCCs. No significant differences in frequencies of genetic alterations were detected between EMS-OCCC and Non-EMS-OCCC groups. CONCLUSION: We successfully characterized the genomic landscape of 15 Korean patients with OCCC. We identified potential therapeutic targets for the treatment of this malignancy.


Subject(s)
Adenocarcinoma, Clear Cell/genetics , Ovarian Neoplasms/genetics , Adenocarcinoma, Clear Cell/ethnology , Adolescent , Adult , Aged , Class I Phosphatidylinositol 3-Kinases/genetics , DNA Copy Number Variations/genetics , DNA-Binding Proteins , Female , Humans , Middle Aged , Mutation/genetics , Nuclear Proteins/genetics , Ovarian Neoplasms/ethnology , Proto-Oncogene Proteins p21(ras)/genetics , Republic of Korea/ethnology , Transcription Factors/genetics , Exome Sequencing , Young Adult
10.
Gynecol Oncol ; 146(2): 351-358, 2017 08.
Article in English | MEDLINE | ID: mdl-28549815

ABSTRACT

OBJECTIVE: To compare the overall survival of non-Hispanic white and Hispanic women with endometrial cancer. METHODS: We performed an observational retrospective cohort study of Hispanic and non-Hispanic women with endometrial cancer from the 2004-2014 National Cancer Database. Baseline characteristics were compared with the Chi-squared test for categorical variables or the Mann-Whitney U test for ordinal or continuous variables. The Kaplan-Meier method was used to estimate unadjusted survival times, which were compared with the log-rank test. Missing data was imputed using multiple imputation with chained equations. A multivariable parametric accelerated failure time model for survival was used. Sensitivity analyses were performed using matched cohort analyses of the overall cohort, and of subgroups based on stage or type. RESULTS: 112,574 non-Hispanic and 6313 Hispanic women met inclusion criteria. Five-year survival was slightly higher for Hispanic women (83.1% (82.1-84.3%) versus 81.4% (81.2-81.7%), P=0.002). Hispanic women were younger, treated at lower volume hospitals, and more often diagnosed with a type II histology and stage II-IV disease compared to non-Hispanic women (all P<0.001). With multivariable adjustment for measured confounders, Hispanic women lived 8% longer than non-Hispanic women (time-ratio (95% CI) 1.08 (1.02-1.14), P=0.01). When bias-reducing matched cohort analyses were used for sensitivity analyses, Hispanic women did not have significantly different survival than non-Hispanic women. CONCLUSION: Hispanic ethnicity was not associated with a clinically meaningful difference in survival among women with endometrial cancer.


Subject(s)
Adenocarcinoma, Clear Cell/mortality , Carcinoma, Endometrioid/mortality , Carcinosarcoma/mortality , Endometrial Neoplasms/mortality , Hispanic or Latino/statistics & numerical data , Neoplasms, Cystic, Mucinous, and Serous/mortality , White People/statistics & numerical data , Adenocarcinoma, Clear Cell/ethnology , Adenocarcinoma, Clear Cell/therapy , Age Distribution , Aged , Carcinoma, Endometrioid/ethnology , Carcinoma, Endometrioid/therapy , Carcinosarcoma/ethnology , Carcinosarcoma/therapy , Databases, Factual , Endometrial Neoplasms/ethnology , Endometrial Neoplasms/therapy , Female , Hospitals, Low-Volume , Humans , Middle Aged , Multivariate Analysis , Neoplasms, Cystic, Mucinous, and Serous/ethnology , Neoplasms, Cystic, Mucinous, and Serous/therapy , Proportional Hazards Models , Retrospective Studies , Survival Rate
11.
Cancer Epidemiol Biomarkers Prev ; 24(9): 1407-15, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26290568

ABSTRACT

BACKGROUND: In contrast with the decreasing incidence seen for most cancers, endometrial cancer has been increasing in the United States. We examined whether the increasing incidence and mortality from endometrial cancer are equally distributed by race/ethnicity and tumor histologic subtype. METHODS: Surveillance, Epidemiology, and End Results (SEER) endometrial cancer incidence and mortality data were obtained from 2000 to 2011. Age-adjusted incidence and incidence-based mortality rates, 95% confidence intervals, and annual percent changes (APC) were calculated. Rate ratios were calculated to compare racial/ethnic groups. Five-year relative survival rates were presented to explore survival by stage at diagnosis. RESULTS: Incidence rates for endometrial cancers are rising across all racial/ethnic groups, with the greatest APC seen among non-Hispanic black (NHB) and Asian women (APC, 2.5 for both). NHB women have significantly higher incidence rates of aggressive endometrial cancers (clear cell, serous, high-grade endometrioid, and malignant mixed Mullerian tumors) compared with non-Hispanic white (NHW) women. Hispanic and Asian women have incidence rates equal to or lower than NHW women for all tumor subtypes. For nearly every stage and subtype, the 5-year relative survival for NHB women is significantly less than NHW women, whereas Hispanic and Asian women have the same or better survival. CONCLUSIONS: Endometrial cancer incidence is increasing for all women, particularly the aggressive subtypes. The disparity associated with excess incidence for these aggressive histologic subtypes and poorer survival is limited to NHB women. IMPACT: Increasing rates of aggressive endometrial cancers may widen the survival disparity between NHW and NHB women.


Subject(s)
Adenocarcinoma, Clear Cell/ethnology , Black or African American/statistics & numerical data , Carcinoma, Endometrioid/ethnology , Carcinosarcoma/ethnology , Endometrial Neoplasms/ethnology , Health Status Disparities , Mixed Tumor, Mullerian/ethnology , Neoplasms, Cystic, Mucinous, and Serous/ethnology , Adenocarcinoma, Clear Cell/mortality , Adenocarcinoma, Clear Cell/pathology , Aged , Aged, 80 and over , Asian/statistics & numerical data , Carcinoma, Endometrioid/mortality , Carcinoma, Endometrioid/pathology , Carcinosarcoma/mortality , Carcinosarcoma/pathology , Endometrial Neoplasms/mortality , Endometrial Neoplasms/pathology , Female , Humans , Incidence , Middle Aged , Mixed Tumor, Mullerian/mortality , Mixed Tumor, Mullerian/pathology , Neoplasm Grading , Neoplasm Staging , Neoplasms, Cystic, Mucinous, and Serous/mortality , Neoplasms, Cystic, Mucinous, and Serous/pathology , United States/epidemiology , White People/statistics & numerical data
12.
Aust N Z J Obstet Gynaecol ; 54(3): 225-30, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24888594

ABSTRACT

BACKGROUND: Ovarian clear cell carcinoma (OCCC) is reportedly more common in Asians than Caucasians. We investigated the epidemiology of OCCC in an Asian population. MATERIALS AND METHODS: Cases of epithelial ovarian cancer (EOC) diagnosed between January 2004 and December 2009 in a gynaecologic oncology unit were studied retrospectively. Patient details and tumour characteristics were retrieved from hospital records and tested for their association with OCCC by univariate and binomial logistic regression analysis. A time trend in the proportion of OCCC among EOC was computed with data from the National Cancer Registry of Singapore (1968-2006). RESULTS: The institutional cohort of 341 cases included 81 OCCC and 260 non-OCCC EOC. Independent risk factors for OCCC were nulliparity (OR = 1.36) and endometriosis (OR = 4.87). Compared with other EOC, OCCC was significantly larger in tumour size (13.5 vs. 11.3 cm), more frequently located unilaterally (84.3 vs. 65.5%), diagnosed at FIGO stage-1 (63.0 vs. 33.9%) and negative for serum CA125 (34.2 vs. 8.2%), and less often (53 vs. 85%) associated with a positive Risk of Malignancy Index. Nation-wide statistics revealed a steady increase in the proportion of OCCC among EOC from 5.2 to 13.4% between 1968 and 2006. The frequency of OCCC in Singapore was higher than American Whites, similar to American Asians but lower than Japanese. CONCLUSION: The difference in epidemiologic and tumour characteristics between OCCC and other EOC was nondiscriminatory. Three distinct ethnic-related clusters of frequency distribution globally and the rising trend in proportion of OCCC in Singapore suggested that ethnic-genetic predisposition and economy-related environmental factors contributed to development of OCCC.


Subject(s)
Adenocarcinoma, Clear Cell/ethnology , Ovarian Neoplasms/ethnology , Adenocarcinoma/ethnology , Adenocarcinoma/pathology , Adenocarcinoma/secondary , Adenocarcinoma, Clear Cell/etiology , Adenocarcinoma, Clear Cell/pathology , Adult , Age Factors , Aged , Aged, 80 and over , Asia/epidemiology , Australia/epidemiology , Endometriosis/complications , Environment , Europe/epidemiology , Female , Humans , Middle Aged , Ovarian Neoplasms/etiology , Parity , Risk Factors , United States/epidemiology
13.
Am J Obstet Gynecol ; 211(6): 627.e1-9, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24954655

ABSTRACT

OBJECTIVE: There are known disparities in endometrial cancer survival with black women who experience a greater risk of death compared with white women. The purpose of this investigation was to evaluate the role of comorbid conditions as modifiers of endometrial cancer survival by race. STUDY DESIGN: Two hundred seventy-one black women and 356 white women who had been diagnosed with endometrial cancer from 1990-2005 were identified from a large urban integrated health center. A retrospective chart review was conducted to gather information on comorbid conditions and other known demographic and clinical predictors of survival. RESULTS: Black women experienced a higher hazard of death from any cause (hazard ratio [HR] 1.51; 95% confidence interval [CI], 1.22-1.87) and from endometrial cancer (HR, 2.42; 95% CI, 1.63-3.60). After adjustment for known clinical prognostic factors and comorbid conditions, the hazard of death for black women was elevated but no longer statistically significant for overall survival (HR, 1.22; 95% CI, 0.94-1.57), and the hazard of death from endometrial cancer remained significantly increased (HR, 2.27; 95% CI, 1.39-3.68). Both black and white women with a history of hypertension experienced a lower hazard of death from endometrial cancer (HR, 0.47; 95% CI, 0.23-0.98; and HR, 0.35; 95% CI, 0.19-0.67, respectively). CONCLUSION: The higher prevalence of comorbid conditions among black women does not explain fully the racial disparities that are seen in endometrial cancer survival. The association between hypertension and a lower hazard of death from endometrial cancer is intriguing, and further investigation into the underlying mechanism is needed.


Subject(s)
Adenocarcinoma/mortality , Black or African American/statistics & numerical data , Diabetes Mellitus/epidemiology , Endometrial Neoplasms/mortality , Hypertension/epidemiology , Obesity/epidemiology , White People/statistics & numerical data , Adenocarcinoma/epidemiology , Adenocarcinoma/ethnology , Adenocarcinoma, Clear Cell/epidemiology , Adenocarcinoma, Clear Cell/ethnology , Adenocarcinoma, Clear Cell/mortality , Adenocarcinoma, Mucinous/epidemiology , Adenocarcinoma, Mucinous/ethnology , Adenocarcinoma, Mucinous/mortality , Aged , Carcinoma, Endometrioid/epidemiology , Carcinoma, Endometrioid/ethnology , Carcinoma, Endometrioid/mortality , Cohort Studies , Comorbidity , Disease-Free Survival , Endometrial Neoplasms/epidemiology , Endometrial Neoplasms/ethnology , Female , Health Status Disparities , Humans , Middle Aged , Prognosis , Proportional Hazards Models , Protective Factors , Retrospective Studies , Risk Factors
14.
Gynecol Oncol ; 133(1): 28-32, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24680588

ABSTRACT

BACKGROUND: We examined the distribution of obesity, diabetes, and race in Type I and Type II endometrial cancers (EC) and their associations with clinical outcomes. METHODS: A multi-institutional retrospective analysis of Type I and II EC cases from January 2005 to December 2010 was conducted. Type I (endometrioid), Type II (serous and clear cell), low grade (LG) (grade 1 and 2 endometrioid), and high grade (HG) (grade 3 endometrioid, serous, clear cell) cohorts were compared. Univariate and multivariate analyses were used to determine time-to-recurrence (TTR), recurrence-free survival (RFS), and overall survival (OS). RESULTS: Type I EC patients were more frequently obese than Type II (66% versus 51%, p<0.0001) and had similar rates of diabetes (25% versus 23%, p=0.69). African-Americans (AA) had higher median BMI than Caucasians in both Type I (p<0.001) and II (p<0.001) ECs, and were twice as likely to have diabetes (p<0.001). In Type I EC, DM was associated with worse RFS and OS in unadjusted and adjusted models (RFS HR 1.38, 95%CI 1.01-1.89; OS HR 1.86, 95%CI 1.30-2.67), but not with TTR. BMI was associated with improved TTR in the adjusted analysis for Type I EC (HR 0.98, 95%CI 0.95-1.0), but not with RFS or OS. There was no association between DM or BMI and outcomes in Type II or HG EC. AA race was not associated with RFS or OS on adjusted analyses in any group. CONCLUSIONS: Obesity and diabetes are highly prevalent in Type I and II ECs, especially in AA. DM was associated with worse RFS and OS in Type I EC. Neither DM nor BMI was associated with outcomes in Type II or HG EC.


Subject(s)
Adenocarcinoma, Clear Cell/ethnology , Carcinoma, Endometrioid/ethnology , Diabetes Mellitus/ethnology , Endometrial Neoplasms/ethnology , Obesity/ethnology , Adenocarcinoma, Clear Cell/therapy , Black or African American/statistics & numerical data , Aged , Asian/statistics & numerical data , Carcinoma/ethnology , Carcinoma/pathology , Carcinoma/therapy , Carcinoma, Endometrioid/therapy , Chemotherapy, Adjuvant , Endometrial Neoplasms/pathology , Endometrial Neoplasms/therapy , Female , Hispanic or Latino/statistics & numerical data , Humans , Indians, North American/statistics & numerical data , Middle Aged , Multivariate Analysis , Radiotherapy, Adjuvant , Retrospective Studies , Treatment Outcome , White People/statistics & numerical data
15.
Gynecol Oncol ; 133(1): 38-42, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24680590

ABSTRACT

OBJECTIVE: Endometrial cancer mortality disproportionately affects black women and whether greater prevalence of obesity plays a role in this disparity is unknown. We examine the effect of race on post-surgical complications, length of stay, and mortality specifically in a morbidly obese population. METHODS: Black and white women with endometrial cancer diagnosed from 1996 to 2012 were identified from the University Pathology Group database in Detroit, Michigan, and records were retrospectively reviewed to obtain clinicopathological, demographic, and surgical information. Analysis was limited to those with a body mass index of 40kg/m(2) or greater. Differences in the distribution of variables by race were assessed by chi-squared tests and t-tests. Kaplan-Meier and Cox regression analyses were performed to examine factors associated with mortality. RESULTS: 97 white and 89 black morbidly obese women were included in this analysis. Black women were more likely to have type II tumors (33.7% versus 15.5% of white women, p-value=0.003). Hypertension was more prevalent in black women (76.4% versus 58.8%, p-value=0.009), and they had longer hospital stays after surgery despite similar rates of open vs minimally invasive procedures and lymph node dissection (mean days=5.4) compared to whites (mean days=3.5, p-value=0.036). Wound infection was the most common complication (16.5% in whites and 14.4% in blacks, p-value=0.888). Blacks were more likely to suffer other complications, but overall the proportions did not differ by race. In univariate analyses, black women had higher risk of endometrial cancer-related death (p-value=0.090). No racial differences were noted in adjusted survival analyses. CONCLUSION: A more complete investigation, incorporating socio-demographic factors, is warranted to understand the effects of morbid obesity and race on endometrial cancer.


Subject(s)
Black or African American/statistics & numerical data , Carcinoma, Endometrioid/surgery , Carcinoma/surgery , Endometrial Neoplasms/surgery , Obesity, Morbid/ethnology , Postoperative Complications/ethnology , White People/statistics & numerical data , Adenocarcinoma, Clear Cell/ethnology , Adenocarcinoma, Clear Cell/mortality , Adenocarcinoma, Clear Cell/surgery , Adult , Carcinoma/ethnology , Carcinoma/mortality , Carcinoma, Endometrioid/ethnology , Carcinoma, Endometrioid/mortality , Endometrial Neoplasms/ethnology , Endometrial Neoplasms/mortality , Female , Humans , Hypertension/ethnology , Length of Stay/statistics & numerical data , Middle Aged , Proportional Hazards Models , Retrospective Studies , Surgical Wound Infection/ethnology , Survival Analysis , Treatment Outcome , Young Adult
16.
Int J Gynecol Cancer ; 24(3): 541-8, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24552897

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the impact of race on the overall survival (OS) and progression-free survival (PFS) of white and African-American patients with uterine clear cell carcinoma (UCCC). METHODS: A retrospective review was conducted of all primary UCCC cases treated at 1 of 4 major gynecologic cancer centers between 1982 and 2012. Patients and tumor characteristics were retrieved from the cancer databases of the respective institutions and based on a retrospective review of the medical records. Differences in the OS and PFS between African-American and white women were compared using the Kaplan-Meier curves and log-rank test for univariate analysis. Cox regression models for the multivariate analyses were built to evaluate the relative impact of the various prognostic factors. RESULTS: One hundred seventy women with UCCC were included in the study, including 118 white and 52 African-American women. Both groups were comparable with respect to age (P = 0.9), stage at diagnosis (P = 0.34), angiolymphatic invasion (P = 0.3), and depth of myometrial invasion (P = 0.84). In the multivariate analyses for known prognostic factors, OS and PFS were significantly different between white and African-American patients in the early-stage disease (hazard ratio [HR], 5.4; 95% confidence interval [CI], 1.2-23.2; P = 0.023 and HR, 3.5; 95% CI, 1.60-7.77; P = 0.0016, respectively) but not in the advanced-stage disease (HR, 0.83; 95% CI, 0.40-1.67; P = 0.61 and HR, 1.5; 95% CI, 0.84-2.78; P = 0.15, respectively). CONCLUSIONS: In the current study, African-American patients have a prognosis worse than that of white patients in early-stage UCCC. We could not prove the same difference in advanced-stage disease.


Subject(s)
Adenocarcinoma, Clear Cell/ethnology , Uterine Neoplasms/ethnology , Adenocarcinoma, Clear Cell/mortality , Adult , Black or African American/statistics & numerical data , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , Middle Aged , Midwestern United States/epidemiology , Retrospective Studies , Uterine Neoplasms/mortality , White People/statistics & numerical data
17.
Int J Gynecol Cancer ; 22(8): 1367-72, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23013731

ABSTRACT

OBJECTIVE: To describe the pattern and frequency of oncogene mutations in white and African American women with endometrial cancer and to determine if racial differences in oncogene mutations exist among women with pathologically similar tumors. METHODS: Patients with endometrial cancer from a large urban hospital were identified through medical records, and representative formalin-fixed paraffin-embedded tumor blocks were retrieved. The study sample included 150 patients (84 African Americans) who underwent total abdominal hysterectomy for endometrial cancer. The Sequenom MassARRAY system and the OncoCarta Assay version 1.0 (Sequenom) were used to test for 238 mutations in 19 common oncogenes. The χ(2) test and the Fisher exact test were used to assess differences in distribution of variables by race and oncogene mutation status. RESULTS: There were 20 mutations identified in 2 oncogenes (PIK3CA and KRAS) in tumors from 19 women (12.7%). Most of the mutations were found in PIK3CA (16/20). Thirteen percent of endometrioid tumors harbored mutations (11 PIK3CA and 2 KRAS) as did 29% of the malignant mixed Mullerian tumors (3 PIK3CA and 1 KRAS). There were no observed mutations in serous, clear cell, or mucinous tumor types. Among low-grade endometrioid cancers, tumors from African American patients were significantly associated with harboring either a KRAS or PIK3CA mutation (P = 0.04), with 7 PIK3CA mutations and all 4 KRAS mutations identified in African American women. CONCLUSIONS: This study provides preliminary evidence that oncogene mutation frequency of some subtypes of histologically similar endometrial carcinoma differ by race. Additional studies are needed to further explore this phenomenon in patients with endometrial carcinoma.


Subject(s)
Black or African American/genetics , Endometrial Neoplasms/ethnology , Mutation/genetics , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins/genetics , White People/genetics , ras Proteins/genetics , Adenocarcinoma, Clear Cell/ethnology , Adenocarcinoma, Clear Cell/genetics , Adenocarcinoma, Clear Cell/pathology , Adenocarcinoma, Mucinous/ethnology , Adenocarcinoma, Mucinous/genetics , Adenocarcinoma, Mucinous/pathology , Adult , Aged , Aged, 80 and over , Class I Phosphatidylinositol 3-Kinases , Cystadenocarcinoma, Serous/ethnology , Cystadenocarcinoma, Serous/genetics , Cystadenocarcinoma, Serous/pathology , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prognosis , Proto-Oncogene Proteins p21(ras) , Retrospective Studies , Survival Rate
18.
Genes Chromosomes Cancer ; 49(9): 791-802, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20607851

ABSTRACT

The goal of this study was to identify recurrent regions of genomic gain or loss in endometrial cancer of the endometrioid type in the context of racial disparities in mortality for this disease. Array comparative genomic hybridization (aCGH) analysis was performed on 80 frozen primary tumors from the Gynecologic Oncology Group (GOG)-210 bank using the RPCI 19K BAC arrays. The 80 patients included 20 African American (AA) Stage I, 20 White (W) Stage I, 20 African American (AA) Stage IIIC/IV, and 20 White (W) Stage IIIC/IV. A separate subset of 220 endometrial cancers with outcome data was used for validation. A 1.6-Mbp region of gain at 1q23 was identified by aCGH in all AA patients and high grade W patients, but not W low grade patients. In the validation arm of 220 patients copy number gain at this region was validated using FISH and locus specific BACs. The number of AA patients in the validation arm was too small to confirm the aCGH association with racial disparity. Kaplan-Meier curves for survival showed a significant difference for gain at 1q23 versus no gain (log rank P = 0.0014). When subdivided into various groups of risk by stage and grade the survival curves showed a decreased survival for high grade and/or stage tumors, but not for low grade and/or stage endometrioid tumors. Univariate analyses for gain at 1q23 showed a significant association (P = 0.009) with survival. Multivariate analysis for gain at 1q23 did not show a significant association with survival (P = 0.14).


Subject(s)
Black or African American/genetics , Comparative Genomic Hybridization , Endometrial Neoplasms/ethnology , Endometrial Neoplasms/genetics , White People/genetics , Adenocarcinoma, Clear Cell/ethnology , Adenocarcinoma, Clear Cell/genetics , Adenocarcinoma, Clear Cell/therapy , Carcinoma, Endometrioid/ethnology , Carcinoma, Endometrioid/genetics , Carcinoma, Endometrioid/therapy , Chromosomes, Human, Pair 1/genetics , Cystadenocarcinoma, Serous/ethnology , Cystadenocarcinoma, Serous/genetics , Cystadenocarcinoma, Serous/therapy , Endometrial Neoplasms/therapy , Female , Gene Amplification , Humans , In Situ Hybridization, Fluorescence , Middle Aged , Survival Rate , Treatment Outcome
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