Study: Genetic alterations may explain HNC survival disparity

Among black Americans, the mortality rate from the most common form of head and neck cancer (HNC) is higher than that of whites with the same cancer, according to a study presented this month at the American Association for Cancer Research conference.

A team of researchers from Johns Hopkins University in Baltimore and the M.D. Anderson Cancer Center in Houston has now identified some genetic mutations in addition to some chemical alterations affecting gene activity, which may help explain this disparity, according to a press release.

The survival gap persists, despite decades of steep declines in deaths from head and neck squamous cell carcinomas among Americans of all races. This decline is largely attributed to the drop in smoking since the mid-1970s.

The researchers analyzed tumor tissue and blood samples from 60 black and 168 white men and women with the disease. The study is believed to be the first and most in-depth analysis of the genetic and epigenetic origins of such common cancers of the lip, mouth, tongue, and throat based on race.

The findings represent what could be the final piece in the survival gap mystery, adding to such well-known contributing factors including education, poverty, limited access to healthcare, and a lack of timely access to treatments, according to lead investigator and genomics epidemiologist Rafael Guerrero-Preston, DrPH, an assistant professor of otolaryngology -- head and neck surgery at Johns Hopkins University School of Medicine.

Among the study's key findings were some 317 epigenetic modifications that are significantly more prevalent in people with HNC and the four most common that were more prevalent in blacks and whites, primarily in a half-dozen biological pathways. One pathway, called TP53, was linked by earlier research from the same Johns Hopkins team to increased rates of HNC in people of all races. Another, NOTCH1, has only recently been tied to squamous cell carcinomas.

Researchers also found several related epigenetic alterations -- molecular modifications of nuclear DNA --- in the PAX pathway, primarily at PAX1 and PAX5, where a chemical process called methylation blocks tumor-suppressing gene activity, silencing the gene.

In the study, survival outcomes for all HNCs were worse for blacks, with some 20% fewer blacks surviving past five years than whites. Three out of 10 people of either race with HNC and both a TP53 mutation and PAX5 methylation do not live as long as people who have had HNC and only a TP53 mutation, the study authors said.

Survival outcomes after five years were two and a half times worse for blacks with PAX5 methylation than whites. People of either race with PAX5 methylation did not live as long as those without.

Moreover, the analysis showed that these related molecular changes were dependent on where the original tumor arose.

For cancers originating in the oropharynx, blacks had significantly more NOTCH1 mutations than whites, at 67% and 14%, respectively. Outside the oropharynx, however, the reverse occurred, with no blacks and 18% of whites having a NOTCH1 mutation.

PAX1 and PAX5 epigenetic alterations were similarly reversed depending on tumor location, with PAX1 methylation in 52% of blacks and 62% of whites in the oropharynx, compared with 70% and 60%, respectively, for tumors originating elsewhere in the head and neck.

TP53 mutations, on the other hand, were significantly higher in blacks than in whites, regardless of tumor site.

As part of the team's analysis, which took three years to complete, researchers decoded and then validated the cancer genetic profiles of all study participants, mostly from the Baltimore region, and then compared the results with genetic information obtained from 279 squamous cell carcinoma tissue samples in the Cancer Genome Atlas database.

Further examination of the genetic and epigenetic modifications are needed before precise survival numbers can be ascribed to any particular genetic mutation or combination of changes, the researchers said. Such detailed findings will require some 200 additional study volunteers for the study to be scientifically accurate.

"Our study results are essential to understanding and eventually remedying head and neck cancer survival disparities between races," Guerrero-Preston said. "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."

Guerrero-Preston plans to not only continue his genetic analyses in blacks, but also to study HNC disparities in Latinos, another ethnic group in which a survival disadvantage, although smaller, persists versus whites.

Page 1 of 116
Next Page