Disparities in Surgical Oncologic Care
Leanne Brown, MD
Resident
Yale New Haven Health System - - New Haven, CT
New Haven, Connecticut, United States
Leanne Brown, MD
Resident
Yale New Haven Health System - - New Haven, CT
New Haven, Connecticut, United States
Leanne Brown, MD
Resident
Yale New Haven Health System - - New Haven, CT
New Haven, Connecticut, United States
Ryan Hagenson, n/a
Biostatistician
Yale University, United States
Jason Sheltzer, PhD
Assistant Professor of Surgery (Oncology) and of Genetics
Yale University, United States
Black patients have higher rates of cancer mortality than any other group. These disparities reflect the interplay of environmental, social, and genetic factors; however, the influence of chromosomal copy number alterations on black patient outcomes is uncertain. The occurrence of whole genome-duplication (WGD), a genomic event associated with aggressive disease, has not been previously investigated in black cancer patients.
Methods:
Genomic and patient data were acquired from tumor sequencing cohorts including MSK-MET, TCGA, and PCAWG. Primary tumors with known WGD status in patients with self-reported race or inferred genetic ancestry were included. Cancer types with at least 75 Black patients were used for subgroup analysis. Within MSK-MET, logistic regression models were created to identify genomic correlates with WGD and race. Clinical associations, including survival and metastasis, were analyzed. Significance testing included Chi-squared for association, Wald test for logistic regression, and logrank for survival.
Results:
Three cohorts were analyzed, MSK-MET (n=13071), TCGA (n=8060), and PCAWG (n=1963). In pan-cancer analysis, Black/African-ancestry patients exhibited higher rates of WGD compared to white/European-ancestry patients within each cohort (MSK-MET: BLACK 29.3% vs. WHITE 26.2%, p=0.04; TCGA: BLACK: 39.4% vs. WHITE 35.5%, p=0.02; PCAWG: AFR 39.3% vs EUR 29.1%, p=0.02). In MSK-MET and TCGA, relative to white patients, Black patients demonstrated a 1.3-fold higher rate of WGD events in breast cancer, a 1.4-fold higher rate in non-small cell lung cancer, and a 2.5-fold higher rate in endometrial cancer. In MSK-MET, WGD events were associated with similar genomic aberrations in both Black and white patients, including TP53 mutations and CCNE1 gains. Black patients had an increased frequency of TP53 mutations compared to white patients in pan-cancer, breast, and endometrial cancer analyses (p< 0.001, all). On pan-cancer analysis, Black race and WGD were associated with worse overall survival (p=0.024, p< 0.0001, respectively), younger ages of diagnosis (p< 0.001, p< 0.002, respectively), first metastasis (p< 0.001, p=0.002, respectively), and death (p< 0.001, p=0.04, respectively). Black race and WGD were associated with increased rates of regional (p< 0.001, both) and distant spread, including intraabdominal (p< 0.001, p=0.001, respectively) and skin metastases (p< 0.001, both).
Conclusions:
The increased incidence of WGD may contribute to known disparate cancer outcomes. WGD may serve as both a prognostic biomarker and potential therapeutic target for Black patients.