Background: Black Americans have a poorer prognosis for clear cell renal cell carcinoma (ccRCC) than white Americans, potentially due in part to differences in tumor biology. In a recent analysis of The Cancer Genome Atlas (TCGA), tumors from black ccRCC patients had a lower rate of mutation in the VHL tumor suppressor gene and lower expression of hypoxia inducible factors (HIF) than tumors from white ccRCC patients. However, as this study was based on a small number of black patients (N=19) and had limited information on patients' medical histories and risk factors profiles, further investigation is needed.

Objective: We evaluated differences in the frequencies of somatic VHL gene mutations and HIF-1α and -2α protein expression between tumors from black and white ccRCC patients.

Methods: The investigation utilized formalin-fixed tissue and data collected from patients participating in a case-control study conducted in Chicago and Detroit. We sequenced VHL using the Ion Torrent platform for tumors from 69 black and 98 white patients, and measured tumor HIF-1α and -2α protein expression for 88 black and 240 white patients using immunohistochemistry.

Results: Black patients' tumors had a lower frequency of VHL mutation than those of white patients (32% vs. 49%; P = 0.03) as well as a lower frequency of above-median HIF-2α expression (33% vs. 56%; P=0.002). HIF-1α expression did not differ by race (P=0.14). These racial differences persisted after multivariable model adjustment for age, sex, hypertension, chronic kidney disease, body mass index, smoking status, stage, grade, and tumor size [VHL mutation: odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.19, 0.98; HIF-2α expression: OR = 0.33, 95% CI = 0.18, 0.61].

Conclusions: Our observation that VHL mutation and high HIF-2α expression are less frequent in ccRCC tumors of black vs. white patients confirms the earlier TCGA finding. These findings suggest that ccRCC in black patients is a fundamentally different disease than ccRCC in white patients.

Citation Format: Catherine L. Callahan, Lee E. Moore, Petra Lenz, Kendra Schwartz, Julie Ruterbusch, Faith Davis, Wong-Ho Chow, W. Marston Linehan, Maria J. Merino, Stephen M. Hewitt, Nathaniel Rothman, Jonathan N. Hofmann, Michael L. Nickerson, Mark P. Purdue. Differences in the frequencies of tumor VHL mutation and HIF-2α expression between black and white patients with clear cell renal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4237.