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Genetic, Epigenetic Changes May Contribute to Survival Differences in African-American Men with Head and Neck Cancers

ATLANTA (GenomeWeb Daily News) – Genetic and epigenetic changes may in part explain survival differences seen between African-American and Caucasian-American men with head and neck cancers.

Based on genomic and epigenomic analyses, Rafael Guerro-Preston, a genomic epidemiologist at Johns Hopkins University School of Medicine, and his team found that African-American men with head and neck cancers more commonly had genetic mutations in TP53 and epigenetic alterations to PAX5, as he presented at the American Association for Cancer Research Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved. Another mutation, in NOTCH1, also appears to be common, but depended on the tissue of origin of the cancer.

"Mutations and methylation used together with information and diet and environmental factors [could be used] to develop oncology solutions," Guerro-Preston said. He added that these findings could be used to develop biomarkers for disease risk and prognosis.

Between 1975 and 2005, the five-year survival rate of head and neck cancer patients increased from 53 percent to 63 percent for all races. But for black men that survival rate remained around 18 percent lower than for non-Latino white men throughout that timeframe.

In their study, Guerro-Preston and his team examined the exome, methylation patterns, and gene expression levels of some 228 people with head and neck squamous cell carcinoma, comprising 60 black and 168 white men and women.

From this, they found that people with head and neck cancers had some 316 genes that were differentially methylated, and a handful of those modifications, particularly in the PAX pathway, were more common in black patients than in white patients. They also noted genetic mutations in p53 and NOTCH1.

The researchers validated their results using nearly 280 head and neck samples from The Cancer Genome Atlas. Guerro-Preston noted, though, that the TCGA does not contain large numbers of samples from African Americans.

The PAX, p53, and Notch1 interact in the same pathway, Guerro-Preston said, with PAX5 upstream of p53. "There are other genes along this pathway that are also impacted," he added.

Survival differences were linked to mutations or epigenetic modifications of these genes. For instance, patients with both a TP53 mutation and PAX5 methylation did not live as long as patients with only a TP3 mutation. Further patients with PAX5 methylation alone did not survive as long as those without, and black patients with PAX5 methylation had two and a half times worse survival outcomes than white patients, Guerro-Preston said.

Guerro-Preston and his colleagues also found that there were differences in the mutations based on the tissue of origin for the cancer and by ethnicity. For example, for oropharynx tumors, which are located at the back of the throat, black patients tended to have more NOTCH1 mutations than white patients, while for other head and neck tumors, white patients were more likely to have NOTCH1 mutations.

Similarly, 52 percent of black patients with oropharyngeal tumors had methylated PAX1 and 70 percent of black patients with other head and neck tumors did, while 62 percent of white patients with oropharyngeal tumors had methylated PAX1 and 60 percent of white patients with other head and neck tumors did.

Mutations in TP53 were more common in black patients than white ones, no matter the site of tumor origin.

Guerro-Preston said that these findings may be useful as biomarkers to gauge not only disease risk and prognosis, but also to better understand how treatment resistance develops.

"We believe this can be useful in this setting of increased healthcare costs, and more combined panels provide part of the solution to increasing healthcare quality and decreasing costs," Guerro-Preston said.

He added that he and his team will be turning to multicenter studies to further validate their findings.