SUO 2017: Mutations And Gene Expression Differences Between African Americans And Non-African Americans With Urothelial Cell Carcinoma

Washington, DC ( While race has been established as a strong predictor in many malignancies, including prostate cancer, there is little evidence in bladder cancer. While African American’s with bladder cancer have been shown to have worse disease specific and overall survival, several factors such as socioeconomic status, access to care, and stage at presentation have been proposed as confounding variables; it remains unclear why this difference exists. However, part of the problem lies in the lack of large studies assessing non-Caucasian patients. Hence, any large series of non-Caucasian patients carries significant value.

In this study, the authors specifically assess the genomic profile differences in patients with upper tract urothelial carcinoma (UTUC), stratified by race – African-American (AA) or non-AA. However, by combining all non-AA races, they muddy the picture. They utilized the publicly accessible The Cancer Genome Atlas (TCGA) Bladder cancer data to obtain and compare mutation type, frequency, signature, and gene expression between African Americans and non-African Americans.

They were able to identify 23 African-American and 323 Caucasian patients with whole genome sequencing and RNA-Seq available from the TCGA dataset. We found no significant difference in the total mutation load between Caucasians and African-Americans (range, median = 240.5 vs. range, median=225.5, p=0.228). There was also no significant difference in frequency of DNA substitution mutations (p=0.33), no different in signature frequency (p=0.3), and no significant difference in mutation frequency of known bladder cancer driver mutations based on race (p=0.41).

They did identify 14 genes with significant differential expression according to race within bladder tissue. Of these genes HIST1H2BD, L1TD1, and LRRC37A2 were associated with worse overall survival (p<0.005, p=0.03, p=0.02, respectively). The pattern of differential gene expression seen in bladder cancer by race also remained relatively consistent for several genes across all cancers in the TCGA.

However, this is clearly very preliminary data with no clinical implications yet. As usual, association does not imply causation. A lot of work is still warranted in this field.

Understanding if there is a difference in disease pathology or difference in healthcare is the first step in bridging the gap.

Limitations / Discussion Points:

  1. Non-AA is too broad – a specific subset analysis of AA, Caucasian, Asian, etc would have been more useful. However, in the substance of the abstract, they restrict to just Caucasians, which is more appropriate.

Presented by: Kalen Rimar, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
Co-Authors: Damiano Fantini, Alexander Glaser, Sarah Psutka, Joshua Meeks

Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Princess Margaret Cancer Centre at @tchandra_uromd at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC