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Biological differences between black, white individuals with breast cancer linked to genetic ancestry
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Forty percent of breast cancer subtype frequency differences between black and white individuals could be explained by germline genetic variants, according to results of an analysis of data from The Cancer Genome Atlas.
“These data could form the basis for the development of molecular targeted therapies to improve clinical outcomes for the specific subtypes of breast cancers that disproportionately affect black women,” Dezheng Huo, MD, PhD, associate professor of epidemiology in the department of public health sciences at The University of Chicago, and colleagues wrote.
Black women have the highest breast cancer mortality rate. Although there are clear racial differences in the distribution of intrinsic breast cancer subtypes, it is unknown how inherent genomic differences contribute to survival disparities.
Huo and colleagues systematically investigated racial differences among 930 patients with breast cancer using data from The Cancer Genome Atlas. The researchers evaluated breast tumor and matched tissue samples for distinctive molecular features including gene expression, protein expression, somatic mutations, somatic DNA copy number alteration and DNA methylation patterns. Breast cancer–free interval also served as a study measure.
The analysis included 154 black individuals of African ancestry (mean age at diagnosis, 55.66 years; 98.1% women) and 776 white individuals of European ancestry (mean age at diagnosis, 59.51 years; 99% women).
Researchers noted some findings mirrored previous population-based research, including that black patients had a younger age a diagnosis and appeared more likely to have ER–negative or nonluminal subtypes.
Black patients had a higher likelihood of basal-like (OR = 3.8; 95% CI, 2.46-5.87) and HER-2–enriched breast cancer subtypes (OR = 2.22; 95% CI, 1.10-4.47), as well as a worse breast cancer–free interval (HR = 1.67; 95% CI, 1.02-2.74).
Analyses revealed 9,232 genes (49.1%) differentially expressed between black and white patients after adjustment for age and batch effects (nominal P < .05).
Overall, researchers observed no difference in the total number of mutations per patient between the two cohorts. However, a greater proportion of black patients than white patients had TP53 mutations (51.7% vs. 31.3%) and fewer had PIK3CA mutations (30.9% vs. 20.4%).
Most molecular differences did not persist after adjustment for intrinsic subtype. Still, researchers identified 16 DNA methylation probes, four DNA copy number segments, one protein and 142 genes that were differentially expressed. This gene-based signature showed good capacity to differentiate breast tumors between black and white patients (cross-validation C index, 0.87).
Using germline genotypes, researchers estimated the heritability of basal vs. nonbasal subtype to be 0.436 (P = 1.5 x 10-14).
Further, black individuals had a higher ER–positive polygenic risk score — which incorporated 89 known susceptibility variants — than white individuals (difference, 0.48; P = 2.8 x 10–11).
“Further studies are warranted to investigate genetic and nongenetic factors that contribute to heterogeneity in the development of distinct breast cancer subtypes, as well as how these factors influence response to therapy and survival outcomes in diverse populations,” the researchers wrote. – by Melinda Stevens
Disclosures: Huo reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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