To back up, Black patients have higher rates of cancer mortality than any other major racial or ethnic group in the US. These disparities may be caused by a combination of social, environmental, and genetic factors that influence cancer development and treatment.
For instance, Black patients tend to get worse treatment – they’re less likely to be seen by the best surgeons and they have to wait longer to start chemotherapy compared to white patients. This undoubtedly contributes to the outcome disparities.
From a genetic perspective, many groups have looked for differences in the frequency of point mutations between patient populations (see the recent paper below). But almost nothing is known about differences in aneuploidy – my lab’s focus.
We assembled a large dataset of tumors from Black and white patients, and we looked for differences in chromosome copy number. We discovered that across several independent cohorts, Black cancer patients were more likely to exhibit whole-genome duplications:
Whole-genome duplications (WGDs) are a genomic event in which a cell’s chromosome complement doubles – they go from ~2N to ~4N. These events are associated with increased genetic heterogeneity and aggressive disease.
We looked in the cancer types for which we had the most Black patients – breast, endometrial, and lung cancer – and we found an increased rate of WGD in these individual lineages as well.
Black patients have historically been under-represented in cancer genome studies, which limits our ability to perform certain sub-analyses. But, we separated patients based on stage and subtype, and we still saw evidence of an increase in WGD frequency.
Recent research has highlighted important differences between racial self-identification and genetic ancestry. We re-ran our analysis and determined that WGD status was also associated with African ancestry:
Next, we sought to uncover the causes of these genomic events. We analyzed Black and white patients, and the same genetic alterations – p53 mutations and CCNE1 amplifications – seemed to drive WGDs in both populations.