Gene mutations and molecular alterations influence HNSCC survival disparities

Certain changes to the PAX gene family may be responsible for survival disparities between black and white men with head and neck cancer. The results were presented at the Sixth American Association for Cancer Research (AACR) Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, December 6-9, 2013, in Atlanta, Georgia.

A handful of genetic mutations and chemical alterations affecting gene activity may help explain why the death rate among blacks continues to be 18% higher than the death rate among whites with the same head and neck cancer. More than 30,000 Americans die each year from some form of head and neck squamous cell carcinoma (HNSCC).

Deaths from HNSCC among Americans of all races have declined sharply for decades. This drop has been attributed to the decline in smoking since the mid 1970s. However, the survival gap, meaning the difference in death rates between races, persists. Poor education, poverty, limited access to health care, and lack of timely access to treatments all contribute to the survival gap and have been studied extensively.

"Our study results are essential to understanding and eventually remedying head and neck cancer survival disparities between races," said Rafael Guerrero-Preston, DrPH, assistant professor of otolaryngology at Johns Hopkins University School of Medicine in Baltimore, Maryland, and at Sidney Kimmel Comprehensive Cancer Center. "The genetic and epigenetic changes we identified can be used for improved risk assessment, early detection, targeted therapy, and patient follow-up for people of all races."

Earlier research from the same group linked the TP53 pathway to increased rates of head and neck cancers in people of all races. Another pathway, NOTCH1, has recently been tied to HNSCC.

Researchers also found several related epigenetic alterations—molecular modifications of nuclear DNA—in the PAX pathway. At PAX1 and PAX5, a chemical process called methylation blocks tumor-suppressing gene activity, silencing the gene.  The presence of a PAX5 methylation decreases survival independent of race.  However, survival outcomes for blacks with a PAX5 methylation were 2.5 times worse than for whites. Presence of both a TP53 mutation and PAX5 methylation decreased survival when compared with the presence of a TP53 mutation alone. Survival outcomes for all head and neck cancers were worse for blacks, who had a 5-year survival rate that was 20% lower than for whites. Moreover, the team's analysis showed that these related molecular changes were dependent on the location of the original tumor.

Guerrero-Preston plans to continue his genetic analyses in blacks and to extend his study of HNSCC survival disparities to Latinos. "Our research goal is to figure out how all of these ethnically predisposing genetic markers interact; how they turn off and on in response to environmental stimuli such as inflammation and lifestyle factors including smoking and nutrition, and how they trigger cancers of the head and neck," Guerrero-Preston said.

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