Genetic ancestry influences tumor biology and survival in head and neck cancers

Genetic ancestry plays a key role in determining the behavior of head and neck tumors and may help explain why African-American patients survive for half as long as their counterparts of European ancestry, according to a new review study led by researchers from the University of Maryland School of Medicine's (UMSOM) Institute for Genome Sciences (IGS) and the University of Maryland Greenebaum Comprehensive Cancer Center (UMGCCC).

Analyzing data from 523 patients stored in The Cancer Genome Atlas (TCGA) --the largest biological database for several cancer types--the study, published in Cancer and Metastasis Reviews, identified the important role of genetic differences in association with gene mutations or changes that drive how quickly tumor cells divide and whether they will respond to chemotherapy or spread to other organs. The researchers found that ancestry, rather than self-identified race, was a stronger predictor of genetic differences between the tumors.

African-American patients survive on average two and a half years after being diagnosed with head and neck squamous cell carcinoma (HNSCC), the technical name for head and neck cancer. European Americans survive an average of 4.8 years, almost twice as long.

HNSCC has been linked to lifestyle risk factors such as tobacco and alcohol use, and infection with the human papillomavirus (HPV). Research has demonstrated that survival differences between those who self-identify as Black and those who self-identify as white may be associated with differences in smoking or drinking rates or delays in diagnosis related to limited access to care.

While these remain essential factors, the new study suggests that tumors arising in patients with different genetic ancestries can exhibit distinct biological features, including changes in key genes that affect how quickly cancer cells grow or how they respond to treatment. These biological differences may help explain variations in treatment response and survival and could support the development of more precise and effective treatment approaches for HNSCC patients. 

This review, led by first author Madeleine Ndahayo, a student researcher at UMSOM, and senior author Daria Gaykalova, PhD, a scientist at IGS and Associate Professor of Otorhinolaryngology – Head and Neck Surgery at UMSOM, underscores the need to examine ancestry-linked tumor biology alongside established social determinants of health like lifestyle habits and socioeconomic status.

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."

Dr. Daria Gaykalova, PhD, scientist at IGS and Associate Professor of Otorhinolaryngology – Head and Neck Surgery at UMSOM

The researchers leveraged data from the TCGA to assess the role of genetic ancestry in the molecular characterization of HNSCC. They found that genetic ancestry influences patterns of tumor mutations, DNA copy gains or losses, and gene activity, suggesting that ancestry-associated biology may shape tumor development and progression. Some of those alterations may be protective, while others may contribute to more aggressive disease.

The study is funded 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).