AACR-The Mark Foundation “Science of the Patient” Grantee Identifies Novel Molecular Subtypes of Head and Neck Cancer in Patients of African Ancestry

Head and neck cancer (HNC), describing cancers of the oral cavity, throat, nose, and sinuses, is the sixth most common cancer worldwide accounting for 300,000 cancer deaths each year. Epidemiological data has shown disparities between HNC screening, detection, treatment, and survival between racial groups (1). In a study recently published in Clinical Cancer Research, the research team led by Dr. Momen-Heravi identified novel genomic alterations and molecular signatures in Black patients that may be related to the environmental, social, and behavioral factors associated with HNC disparities.

Fatemeh Momen-Heravi, DDS, MPH, PhD, MS is an Associate Professor at the College of Dental Medicine, and Director of the head and neck cancer research group at the Herbert Irving Comprehensive Cancer Center, Columbia University. She received the AACR-The Mark Foundation for Cancer Research “Science of the Patient” (SOP) Grant in 2020 to investigate the molecular features of HNC tumors, specifically in patients with African ancestry.

Dr. Momen-Heravi and her colleagues studied 1099 patients with HNC, including 95 Black patients and 1004 White patients. To avoid self-reported biases, the patients within the study were genetically assigned as African ancestry (Black patients) or European ancestry (White patients). Confirming previous findings, they found that Black patients were diagnosed with HNC at a younger age, had an increased rate of metastasis, and worse overall survival than White patients. There were also differences in tumor location sites between Black and White patients with Black patients showing a higher level of tumors in the larynx and lower percentage of tongue tumors than White patients.

The research group then used several approaches to dig deeper into the genetic and molecular changes behind these differences; assessing mutation, copy number alteration, methylation, and expression of genes in both patient groups. They identified numerous genes of interest, such as TP53 and RET, which were mutated at a higher frequency in the Black patient pool. However, to fully understand the significance of these genes in HNC, the research group highlight that further investigation is required.

By performing functional pathway analysis of gene expression data, they found the c-MYC pathway was enriched in Black patients compared to White patients. Increased expression or copy-number gain of c-MYC has previously been linked to a worse prognosis of HNC (2). Given this, they hypothesized that the frequent upregulation of c-MYC in Black patients may at least in part explain the development of more aggressive tumors. To investigate this further, the research group measured c-MYC signaling activation by IHC in an independent cohort of HNC tumor samples from 36 Black patients and 36 White patients. In this cohort, the tumors of Black patients had significantly higher c-MYC protein expression than White patients. Furthermore, after quantifying c-MYC staining and patient samples were dichotomized into groups with high or low c-MYC, they found that those with high c-MYC had worse survival outcomes.

Explaining the importance of their findings, Dr. Momen-Heravi said, “Our findings have the potential to help develop more individualized and targeted screening, diagnostic, and treatment modalities to improve health outcomes for Black patients with head and neck cancer. By identifying molecular characteristics and biomarkers associated with the development of head and neck cancer in minority populations, I hope to bring attention to the importance of studying diverse populations and expanding personalized medicine.”

Sharing how important the AACR-The Mark Foundation “Science of the Patient” (SOP) Grant was to her research, Dr. Momen-Heravi said, “With the help of this award, I have been able to conduct more comprehensive studies into the molecular basis and genomics of head and neck cancer disparities in Black populations. Furthermore, being a recipient of this prestigious award opened new avenues of collaboration, allowing me to reach a larger audience and extend the impact of my research. Finally, the grant has provided me with the resources needed to take on more ambitious projects in the future, further advancing progress in the fight against head and neck cancer. All in all, I am incredibly grateful for all the support I have received from the AACR and look forward to furthering our shared mission of eliminating disparities in cancer outcomes.”

References:

1. DeSantis CE, Siegel RL, Sauer AG, Miller KD, Fedewa SA, Alcaraz KI, et al. Cancer statistics for African Americans, 2016: Progress and opportunities in reducing racial disparities. CA Cancer J Clin 2016; 66:290-308. doi: 10.3322/caac.21340.
2. Field JK, Spandidos DA, Stell PM, Vaughan ED, Evan GI, Moore JP. Elevated expression of the c-myc oncoprotein correlates with poor prognosis in head and neck squamous cell carcinoma. Oncogene 1989;4:1463–8.