PD14-09: Analyzing Differences in Somatic Mutations in Localized Bladder Cancer Patients by Race and Sex: An Analysis of Data from the cBioPortal for Cancer Genomics

Kelsey Baker*, Yaw Nyame, Mary Redman, Robert Montgomery, Petros Grivas, Jonathan Wright, Seattle, WA

Introduction: Disparities in bladder cancer outcomes exist by race/ethnicity and sex. However, limited data exists on differences in tumor biology by these factors. We hypothesize that social, environmental, and biologic differences that exist by race and sex are likely to drive different biologic phenotypes in bladder cancer. This study aimed to evaluate if these differences existed in a large, multi-institutional cohort.

Methods: Nine urothelial cancer studies and 122 genes (113 actionable, 31 DNA damage repair (DDR)) that are commonly associated with bladder cancer were identified in the cBioPortal platform. Patients were excluded if they had low-grade disease or had no demographic data. Multivariable logistic regression, adjusted for age and disease stage, was performed to evaluate the association between mutation status and race/sex. P < 0.05 was used for statistical significance. No adjustments were made for multiple comparisons.

Results: Mutation and demographic data for 880 patients was included for analysis.  The median age in this cohort was 67 years (range: 25-98), with 216 (25%) female, 423 (48%) White, 74 (8%) non-White, and 383 (44%) unknown race.  Muscle-invasive disease was present in 78% of cases. The median total mutation count was 74 (IQR: 11-186). At least one actionable gene mutation and at least one DDR gene mutation was found in 832 (95%) and 392 (45%) patients, respectively.

Somatic mutated gene prevalence differed by sex and race (Table 1). Males in this cohort were more likely to have ARID1A, ATM, CHD6, ERBB2, NCOR1, and FLT4 mutations. White race was associated with higher likelihood of having ARID1A, EP300, and TP53 mutations and lower likelihood of having HRAS mutations.

Conclusions: Differences in somatic mutations existed by both race and sex in a large cohort of patients with bladder cancer. These findings are limited by poor representation of females, non-White patients, limited demographic data collection, and retrospective design. Intentional efforts are needed to build representative patient cohorts and more complete demographic data collection to assess the role of social, environmental, and sex-specific biologic drivers of bladder cancer.

Source of Funding: This study was supported by institutional funding through the MXD Championships (JLW).