Patients with renal cell carcinoma (RCC) have different clinical presentations, extent of disease, and germline and somatic alterations on the basis of genetic ancestry, according to research presented at IKCS North America 2022.
Researchers evaluated the potential effects of genetic ancestry in 953 patients with clear cell and non-clear cell RCC.
The patients were of European (78%), African (5%), East Asian (3%), South Asian (2%), Native American (<1%), and admixed (12%) ancestries. The patients had a median age of 56 years (range, 19-89) at diagnosis, 72% were men, and 72% had localized disease.
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The groups differed in their rate of distant metastasis, which was highest among the East Asian (45%) and African (40%) cohorts compared with the other groups (range, 28%-29%).
Similarly, International Metastatic RCC Database Consortium (IMDC) risk differed across ancestral groups. The African (0%), South Asian (13%), and East Asian (16%) cohorts were less likely to have favorable IMDC risk compared with the European and admixed cohorts (31% for both).
Clear cell RCC was most common for patients with South Asian ancestry (74%), followed by European (66%), East Asian (65%), admixed (43%), and African (26%) ancestries. Papillary disease was most common for patients with African ancestry (30%), followed by admixed (17%), European (9%), East Asian (9%), and South Asian (0%) ancestries.
Overall, 17% of patients had germline alterations. The rate of germline mutations was highest for individuals with African ancestry (23%), but only FH and BAP1 alterations were observed in this cohort.
For patients of European ancestry, 17% had germline alterations in 12 genes. The most common germline alterations in this group were seen in CHEK2, FH, MUTYH, APC, and ATM. Germline alterations were seen in 8% of patients in the East Asian cohort and 18% of the admixed cohort.
In the clear cell RCC cohort, most patients (95%) had somatic mutations, with the highest rates occurring among Native Americans and East Asians (both 100%), followed by the European (95%), admixed (94%), South Asian (93%), and African (75%) cohorts.
Among the most common somatic alterations (VHL, PBRM1, SETD2, BAP1, and KDM5C), no BAP1 alterations were observed in the East Asian group, and no KDM5C alterations were observed in the African, South Asian, and Native American groups.
“Analyzing this large cohort by ancestry revealed differences in clinical germline and somatic data,” said study presenter Ritesh Kotecha, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.
“We see differences, particularly in clinical presentation, histology, IMDC risk distribution, and extensive disease at the time of presentation. There should be a strong initiative to improve research in underrepresented groups.”
Disclosures: Dr Kotecha declared affiliations with Allogene, Novartis, Pfizer, Takeda, and Eisai.
Reference
Kotecha R, Knezevic A, Arora K, et al. Genetic ancestry and molecular correlations in patients with kidney cancers. Presented at IKCS North America 2022. November 4-5, 2022. Abstract 8.
