Racial Variation in RCC: Toward Ancestry-Informed Kidney Care

A cohort study recently published in Cancer examined renal cell carcinoma (RCC) histology and outcomes by race, revealing several key clinical, histologic, and transcriptomic differences between Black and non-Black patients in France that can be leveraged for ancestry-informed kidney care.¹

A notable histologic difference was that Black patients were more likely to have rare and aggressive non–clear cell kidney cancers compared with non-Black patients. Clear cell RCC, the predominant subtype across the entire study cohort (68%), was more prevalent among non-Black patients (68.8% vs 47.6%; OR, 0.41; P <.001), whereas papillary RCC was more common among Black patients (23.1% vs 11.8%; OR, 2.23; P <.001). Black patients were also more likely to have rare subtypes, including translocation RCC, clear cell papillary renal cell tumor, renal medullary carcinoma, and fumarate hydratase–deficient RCC (OR ≥ 2, all subtypes), as well as benign renal conditions.

Black patients also tended to fare better than non-Black patients in the short term, which may be reflective of their tendency to be diagnosed at a younger age (median, 58 years vs 63 years; P <.001) with smaller tumors (T1-2: 85.2% vs 71.8%, respectively; P <.001) at earlier stages (stages I-II: 85.1% vs 67.2%; P <.001), thereby undergoing partial nephrectomy more frequently (70.6% vs 62.3%; P =.002). Black patients appeared to have prolonged distant recurrence–free survival compared with non-Black patients (HR, 0.54; 95% CI, 0.33-0.91; P =.019); however, investigators did not observe any significant differences in disease-specific survival (P =.429) and, after adjusting for clinical factors, ultimately did not find an association between race and survival.

Black and non-Black patients also differed in terms of baseline clinical characteristics. Black patients had a higher rate of comorbidities compared with non-Black patients, including diabetes (22.6% vs 16.5%, respectively; P =.004), chronic kidney disease (13.6% vs 6.9%; P <.001), and hemodialysis use (3.3% vs 1.3%; P =.004). The rate of obesity was also significantly higher among Black patients (30.6% vs 25.4%; P =.043), but smoking and anticoagulant use were less frequent compared with non-Black patients.

At the molecular level, transcriptomic profiling of a single-nucleus RNA-seq data set of renal epithelial cells revealed variations in gene regulation by race, with hemoglobin-related HPR and chemokine-related ACOT1 upregulated in Black patients, and ADIPOQ, an adipocyte marker, upregulated in White patients.

“Although race was not a prognostic factor after adjusting for clinical variables, our findings support the value of ancestry-informed cancer research and highlight the need for improved diagnostic strategies to detect rare RCC subtypes,” said Lu et al, study investigators, in the manuscript.¹

How was the study population constructed?

The study population was derived from the UroCCR database, a French national registry of kidney cancer. Patients were excluded if they had an unconfirmed diagnosis or detectable tumor, unknown race, and undefined RCC subtype and were not eligible for surgery, the latter of which was cited as a limitation by the authors, as this criterion may have underrepresented advanced-stage patients.

The final study population included 9404 patients, including 338 Black and 9066 non-Black patients, whose diagnoses were confirmed by partial or radical nephrectomy across 30 tertiary centers between December 1987 and May 2024. Among this population, 8483 had RCC across 16 histologic subtypes.

Investigators used medical chart documentation to classify patients into Black and non-Black groups. A limitation of this classification, according to the authors, is that this dichotomous nature of race classification results in data aggregation, potentially masking heterogeneity of diverse racial/ethnic subgroups within both Black and non-Black groups. Furthermore, the limited number of Black patients had reduced statistical power for several analyses.

What are the key takeaways?

Historically, the abundance of scientific evidence documenting racial differences in kidney cancer has originated from the United States. As the United States is vastly racially heterogeneous and utilizes a mixed, multipayer health care system, results of these studies may not be generalizable to populations in countries with different racial distributions and health care systems. This study was motivated by a lack of research characterizing such differences in the European population, particularly in settings with a universal health care system.

In contrast to US studies, which largely attribute poorer survival among Black patients to social determinants of health and structural inequities limiting access to care,² the differences observed in this study show a divergent pattern. According to the authors, the lack of significant survival disparities by race may be reflective of an equitable health care system.

Overall, understanding such patterns may help inform and drive precision treatment strategies for patients with RCC.

“Together, these findings provide an epidemiologic and molecular framework for ancestry-informed kidney cancer research and care,” said Lu et al.

REFERENCES

1. Lu X, Bernhard J, Margue G, et al. Racial differences in kidney cancer histology and outcome: a nationwide study from the UroCCR Cohort. Cancer. 2025;131(20):e70120. doi:10.1002/cncr.70120

2. Eley JW, Hill HA, Chen VW, et al. Racial differences in survival from breast cancer. results of the National Cancer Institute Black/White Cancer Survival Study. JAMA. 1994;272(12):947-954. doi:10.1001/jama.272.12.947