Objective: Emerging research from the SEER database suggests that African American (AA) patients with thyroid cancer have worse outcomes than their White (W) counterparts, even when controlling for age, sex, and socioeconomic factors. Few studies have explored the genetic and morphologic landscape of thyroid cancer in AA patients, highlighting the need for an enhanced understanding of the molecular underpinnings of thyroid cancer across diverse study cohorts. Here, we hypothesize that the landscape of genetic drivers of thyroid cancer in AA patients is different from that of W patients.

Methods: We analyzed the frequency of BRAFV600E and RAS driver mutations and distribution of histopathologic subtypes for thyroid cancer patients by reported race in two large thyroid cancer sequencing cohorts: the Tempus multimodal database and The Cancer Genome Atlas.

Results: While papillary thyroid carcinomas (PTC) are the most common histologic subtype overall in both cohorts, the Tempus multimodal database demonstrates increased prevalence of follicular thyroid carcinoma in AA patients. There is a corresponding decreased prevalence of PTC in AA patients relative to the entire Tempus multimodal database, and within the PTC category, AA patients have increased prevalence of follicular variant PTC and decreased prevalence of classical papillary histology. Follicular-patterned thyroid cancers are typically associated with RAS mutations and fewer lymph node metastases. Compared to the entire Tempus multimodal database, AA patients show decreased frequency of BRAF V600E and increased frequency of RAS mutations. Consistent with the RAS mutations, AA patients show fewer lymph node metastases. AA patients in
a smaller cohort, The Cancer Genome Atlas, also trend toward increased follicular-patterned tumors.

Discussion/Conclusion: Altogether, we have identified a shift in the landscape of thyroid cancer in AA patients toward RAS-driven follicular-patterned tumors, which could be a result of both social determinants of health and genetic factors contributing to different disease phenotypes. The underlying cause of these differences should be further evaluated with the goal of rethinking how we diagnose, prognose, and treat thyroid cancer for diverse populations.

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