Certain genetic alterations to the PAX gene family may be responsible for survival disparities seen between African-American and non-Latino white men with head and neck cancer, according to results presented here at the Sixth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, held Dec. 6-9.
“During the last 30 years, the overall five-year relative survival rates for head and neck squamous cell carcinoma (HNSCC) have increased, but despite that, the gap in overall survival rates between non-Latino white patients and African-American patients has remained unchanged,” said Rafael Guerrero-Preston, Dr.P.H., assistant professor at Johns Hopkins University in Baltimore, Md. “This disparity may be due to differences in genetic and epigenetic alterations among African-American patients.”
To test this theory, Guerrero-Preston and colleagues performed a two-stage epigenomic study. In the stage-one discovery phase, the researchers used next-generation sequencing and array-based technologies to evaluate 107 HNSCC samples. In the stage-two validation phase, they validated the findings of the discovery phase and evaluated their effect on survival rates in 279 patient samples from The Cancer Genome Atlas project.
“Our results highlight the differential genomic and epigenomic alterations in PAX, NOTCH, and TP53 pathways between African-American and non-Latino white HNSCC patients, which underlie the complex biology of morphologically similar tumors and explain HNSCC survival disparities,” Guerrero-Preston said. “If further validated in larger cohorts, these discoveries could be used to develop genomic and epigenomic panels that will enable more treatment options, a reduction in treatment cost, and improvement in survival rates for patients with HNSCC.”
The researchers found that African-American HNSCC patients had higher frequencies of p53, FBXW7, and NOTCH1 mutations and no differences in PAX1 or PAX5 methylation across all tumor sites combined. However, when they looked at data based on each tumor site, some differences were discovered.
African-American patients with HNSCC had higher ZIC4, PLCB1, and PAX5 promoter methylation and p53 mutations compared with non-Latino white patients. African-American patients also had no NOTCH1 mutations in nonoropharynx HNSCC. However, in the oropharynx, African-American patients had a higher frequency of combined NOTCH1 mutations and PAX1 methylation.
In contrast, non-Latino white patients with HNSCC had a higher frequency of PAX5 promoter methylation and combined p53 mutation or PAX5 methylation in the oropharynx compared with African-American patients.
All patients with greater PAX5 methylation and p53 mutations had worse overall survival, the researchers found.
Source: American Association for Cancer Research