Dataset Information

Racial differences in endometrial cancer molecular portraits in The Cancer Genome Atlas.

ABSTRACT: Endometrial cancer (EC) is now the most prevalent gynaecological malignancy in the Western world. Black or African American women (BoAA) have double the mortality of Caucasian women, and their tumours tend to be of higher grade. Despite these disparities, little is known regarding the mutational landscape of EC between races. Hence, we wished to investigate the molecular features of ECs within The Cancer Genome Atlas (TCGA) dataset by racial groupings. In total 374 Caucasian, 109 BoAA and 20 Asian patients were included in the analysis. Asian women were diagnosed at younger age, 54.2 years versus 64.5 years for Caucasian and 64.9 years for BoAA women (OR 3.432; p=0.011); BoAA women were more likely to have serous type tumors (OR 2.061; p=0.008). No difference in overall survival was evident. The most frequently mutated gene in Caucasian and Asian tumours was PTEN (63% and 85%), unlike BoAA cases where it was TP53 (49%). Mutation and somatic copy number alteration (SCNA) analysis revealed an enrichment of TP53 mutations in BoAAs; whereas POLE and RPL22 mutations were more frequent in Caucasians. Major recurrent SCNA racial differences were observed at chromosomes 3p, 8, 10, and 16, which clustered BoAA tumors into 4 distinct groups and Caucasian tumors into 5 groups. There was a significantly higher frequency of somatic mutations in DNA mismatch repair genes in Asian tumours, in particular PMS2 (p=0.0036). In conclusion, inherent racial disparities appear to be present in the molecular profile of EC, which could have potential implications on clinical management.

SUBMITTER: Guttery DS

PROVIDER: S-EPMC5908308 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Racial differences in endometrial cancer molecular portraits in The Cancer Genome Atlas.

Guttery David S DS Blighe Kevin K Polymeros Konstantinos K Symonds R Paul RP Macip Salvador S Moss Esther L EL

Oncotarget 20180330 24

Endometrial cancer (EC) is now the most prevalent gynaecological malignancy in the Western world. Black or African American women (BoAA) have double the mortality of Caucasian women, and their tumours tend to be of higher grade. Despite these disparities, little is known regarding the mutational landscape of EC between races. Hence, we wished to investigate the molecular features of ECs within The Cancer Genome Atlas (TCGA) dataset by racial groupings. In total 374 Caucasian, 109 BoAA and 20 Asi ...[more]

PMID: 29682207

Similar Datasets

Project description:To determine whether (1) black and white women with endometrial cancer were treated by different surgical specialties and in different types of hospitals and (2) differences in specialty and hospital type contributed to racial differences in survival.Retrospective cohort study of 12,307 women aged 65 years and older who underwent surgical treatment of endometrial cancer between 1991 and 1999 in the 11 Surveillance Epidemiology and End Results registries.Black women were more likely to have a gynecologic oncologist to perform their surgery and to be treated at hospitals that were higher volume, larger, teaching, National Cancer Institute centers, urban, and where a greater proportion of the surgeries were performed by a gynecologic oncologist. In unadjusted models, black women were over twice as likely as white women who died because of cancer (hazards ratio [HR]: 2.33), but nearly all of the initial racial difference in survival was explained by differences in cancer stage, and grade as well as age and comorbidities at presentation (adjusted HR: 1.10). Surgical specialty was not associated with survival and, of the hospital characteristics studied, only surgical volume was associated with survival (P < 0.005). Adjusting for hospital characteristics did not change the racial difference in survival (HR: 1.10). Adjustment for the specific hospital where the woman was treated eliminated the association between race and surgeon specialty and slightly widened the residual racial difference in survival (HR: 1.23 vs. 1.10).In contrast to several studies suggesting that blacks with breast cancer, colon cancer, or cardiovascular disease are treated in hospitals with lower quality indicators, black women diagnosed with endometrial cancer in Surveillance Epidemiology and End Results regions between 1991 and 1999 were more likely to be treated by physicians with advanced training and in high volume, large, urban, teaching hospitals. However, except for a modest association with hospital surgical volume, these provider and hospital characteristics were largely unrelated to survival for women with endometrial cancer. The great majority of the difference in survival was explained by differences in tumor and clinical characteristics at presentation.

Project description:UnlabelledViruses are causally associated with a number of human malignancies. In this study, we sought to identify new virus-cancer associations by searching RNA sequencing data sets from >2,000 patients, encompassing 21 cancers from The Cancer Genome Atlas (TCGA), for the presence of viral sequences. In agreement with previous studies, we found human papillomavirus 16 (HPV16) and HPV18 in oropharyngeal cancer and hepatitis B and C viruses in liver cancer. Unexpectedly, however, we found HPV38, a cutaneous form of HPV associated with skin cancer, in 32 of 168 samples from endometrial cancer. In 12 of the HPV38-positive (HPV38(+)) samples, we observed at least one paired read that mapped to both human and HPV38 genomes, indicative of viral integration into the host DNA, something not previously demonstrated for HPV38. The expression levels of HPV38 transcripts were relatively low, and all 32 HPV38(+) samples belonged to the same experimental batch of 40 samples, whereas none of the other 128 endometrial carcinoma samples were HPV38(+), raising doubts about the significance of the HPV38 association. Moreover, the HPV38(+) samples contained the same 10 novel single nucleotide variations (SNVs), leading us to hypothesize that one patient was infected with this new isolate of HPV38, which was integrated into his/her genome and may have cross-contaminated other TCGA samples within batch 228. Based on our analysis, we propose guidelines to examine the batch effect, virus expression level, and SNVs as part of next-generation sequencing (NGS) data analysis for evaluating the significance of viral/pathogen sequences in clinical samples.ImportanceHigh-throughput RNA sequencing (RNA-Seq), followed by computational analysis, has vastly accelerated the identification of viral and other pathogenic sequences in clinical samples, but cross-contamination during the processing of the samples remain a major problem that can lead to erroneous conclusions. We found HPV38 sequences specifically present in RNA-Seq samples from endometrial cancer patients from TCGA, a virus not previously associated with this type of cancer. However, multiple lines of evidence suggest possible cross-contamination in these samples, which were processed together in the same batch. Despite this potential cross-contamination, our data indicate that we have detected a new isolate of HPV38 that appears to be integrated into the human genome. We also provide general guidelines for computational detection and interpretation of pathogen-disease associations.

Project description:PurposeThere are racial and ethnic differences in endometrial cancer incidence and mortality rates; compared with Non-Hispanic White women, Black women have a similar incidence rate for endometrial cancer, but their mortality is higher. Pacific Islander women may also have worse outcomes compared to their White counterparts. We assessed tumor characteristics and adjuvant therapy by racial and ethnic group among endometrial cancer patients treated within the Military Health System, an equal access healthcare organization.MethodsWe retrospectively identified women diagnosed with invasive endometrial cancer among US Department of Defense beneficiaries reported in the Automated Central Tumor Registry database (year of diagnosis: 2001-2018). We compared tumor characteristics and receipt of adjuvant therapy across racial and ethnic groups using Chi-square or Fisher tests. Hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of all cause mortality were calculated using Cox proportional hazards regression models adjusting for age at diagnosis, adjuvant therapy, histology and stage.ResultsThe study included 2574 endometrial cancer patients [1729 Non-Hispanic White, 318 Asian, 286 Black, 140 Pacific Islander and 101 Hispanic women]. Among all cases, a higher proportion of Black patients had non-endometrioid histology (46.5% versus ≤ 29.3% in other groups, P < 0.01) and grade 3-4 tumors (40.1% versus ≤ 29.3% in other groups, P < 0.01). In multivariable Cox models, compared with Non-Hispanic White cases, Black endometrial cancer patients had a higher mortality risk (HR 1.43, 95% CI, 1.13-1.83). There was no difference in mortality risk for other racial and ethnic groups.ConclusionBlack patients with endometrial cancer presented with more aggressive tumor features and they had worse overall survival compared with patients in other racial and ethnic groups. Further study is needed to better direct preventive and therapeutic efforts in order to correct endometrial cancer disparities in the future.

Dataset Information

Racial differences in endometrial cancer molecular portraits in The Cancer Genome Atlas.

Publications

Racial differences in endometrial cancer molecular portraits in The Cancer Genome Atlas.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets