Genetic Ancestry Emerges as Key Factor in Head and Neck Tumor Behavior

A new review study, led by researchers from the University of Maryland School of Medicine (UMSOM) and the University of Maryland Greenebaum Comprehensive Cancer Center (UMGCCC), indicates that genetic ancestry is a key factor in the behavior of head and neck tumors. This factor may contribute to the observed survival disparity, where African-American patients survive for approximately half the duration of European-American patients.

The study, published in Cancer and Metastasis Reviews, analyzed data from 523 patients within The Cancer Genome Atlas (TCGA) database. Its findings highlighted the significance of genetic differences linked to gene mutations that influence tumor cell division rates, chemotherapy response, and metastasis. Genetic ancestry was identified as a more robust predictor of these tumor-related genetic differences compared to self-identified race.

African-American patients with head and neck squamous cell carcinoma (HNSCC) have an average survival of two and a half years post-diagnosis, while European-American patients survive for an average of 4.8 years.

Beyond Lifestyle: Uncovering Biological Drivers

Previous research has associated HNSCC with lifestyle factors like tobacco and alcohol use, and HPV infection. Survival differences between self-identified Black and white individuals have also been linked to varying smoking and drinking rates, or delays in diagnosis due to limited healthcare access.

While these remain significant factors, the new study suggests that tumors in patients with different genetic ancestries can exhibit distinct biological features. These include alterations in key genes that affect cancer cell growth and treatment response. These biological distinctions could explain variations in treatment outcomes and survival, potentially supporting the development of more precise HNSCC treatments.

A Call for Precision Medicine

Madeleine Ndahayo, a student researcher at UMSOM, led the review, with senior authorship by Dr. Daria Gaykalova, a scientist at IGS and Associate Professor of Otorhinolaryngology – Head and Neck Surgery at UMSOM. The study emphasizes the necessity of examining ancestry-linked tumor biology in conjunction with established social determinants of health.

Dr. Gaykalova stated:

"Genetic ancestry reflects biologically encoded variation in DNA. This review reinforces that social factors matter, but it also shows that biological drivers linked to ancestry must be considered if we want truly effective precision medicine."

Delving Deeper into Tumor Biology

The researchers utilized TCGA data to evaluate genetic ancestry's role in HNSCC's molecular characteristics. They observed that genetic ancestry influences patterns of tumor mutations, DNA copy number alterations, and gene activity. This implies that ancestry-associated biology may shape tumor development and progression. Some of these alterations may offer protection, while others could lead to more aggressive disease.

Funding

Funding for the study was provided by the American Cancer Society, the National Institute of Dental and Craniofacial Research (NIDCR), the National Cancer Institute (NCI), and the National Institutes of Health (NIH).