African American (AA) patients with head and neck squamous cell carcinomas (HNSCC) have significantly worse outcomes than White patients: the median survival time following diagnosis for AAs with HNSCC is strikingly and significantly shorter (~20 months) than that of their White counterparts (~40 months). Social determinants of health cannot completely explain this health disparity as the outcomes have been shown to be independent of socioeconomic status, comorbidities, clinical characteristics, and treatment modality. In order to discover what potential biology may be underlying this health disparity, we sequenced samples from 16 AA patients with HNSCC and found a germline JAK3 single nucleotide polymorphism (SNP; c.394C>A; protein P132T, rs3212723 henceforth) in 25% of the samples (all laryngeal cancers). We confirmed rs3212723 with targeted sequencing and found it in 8% of patients in a larger validation cohort—all of whom were AAs with HNSCC (either pharyngeal or laryngeal cancers).
In order to add support to our preliminary results, we are assessing the frequency of rs3212723 in patients (of all races) with/out HNSCC using larger databases and a variety of complimentary bioinformatics approaches. Specifically, we are interrogating Vanderbilt’s BioVU, The Cancer Genome Atlas (TCGA), and the Southern Community Cohort Study (SCCS) using both genetic (rs3212723) and phenomic (HNSCC) approaches. In BioVU, we have identified 676 patients (31 homozygotes, 645 heterozygotes) with rs3212723, 92% of which are AA. In TCGA, of the 528 incident cases of HNSCC, 48 (9%) are AA. In the SCCS, we have identified 214 cases of HNSCC, all of which are AA. By creating matched (at the SNP, disease, and racial levels) cohorts of patients using each of these databases, we are determining whether rs3212723 is associated with HNSCC incidence, survival, and race.
We aim to build a significant association between rs3212723, HNSCC, and race that could thereafter be testing in prospective precision medicine studies. Precision medicine remains elusive in HNSCC because of its poorly understood biology. As such, these studies have the potential to provide an innovative approach to precision medicine in HNSCC: by identifying a germline risk variant that could help screen, stratify, and intervene in an at-risk population.