Researchers at Johns Hopkins and in Texas have discovered genetic mutations in African Americans as well as some chemical alterations affecting gene activity which may explain why the death rate among African-Americans from the most common form of head and neck cancer is 18 percent higher above the death rate of caucasians with the same cancer.
According to the researchers, the survival gap, despite decades of steep declines in deaths from head and neck carcinomas among all Americans, is largely attributed to the drop in smoking since the mid-1970s.
The current research looked at tumor tissue and blood samples from 60 black and 168 caucasian males and females with the disease may be the first and most in-depth analysis of the genetic and epigenetic origins of cancers such as lip, mouth, tongue and throat based on race. It is reported that more than 30,000 Americans die every year from some form of head and neck squamous cell carcinoma.
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According to Dr. Rafael Guerrero-Preston, P.H., lead study investigator and genomics epidemiologist at the Johns Hopkins University School of Medicine and its Sidney Kimmel Comprehensive Cancer Center, his team’s findings could possibly be the final piece in the survival-gap. The current study is contributing to well-studied and well-known contributing factors such as poor education, poverty, limited access to health care and untimely access to treatments.
Guerrero-Preston notes, “Our study results are essential to understanding and eventually remedying head and neck cancer survival disparities between races. 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”. The team of researchers found 317 epigenetic modifications more prevalent in individuals with head and neck cancers and the four most common that are more prevalent in blacks and caucasians, mostly in a half-dozen biological pathways.
One particular pathway known as TP53, was discovered earlier by the same Johns Hopkins group to increased rates of head and neck cancers in individuals of all races. Another pathway, NOTCH1, was more recently tied to squamous cell carcinomas. They also discovered several epigenetic changes involving molecular alterations of nuclear DNA. This was in the PAX pathway (PAX1 and PAX5) where a chemical process known as methylation blocks tumor suppressor gene activity, putting quietus to the gene.
The researchers report survival outcomes for all head and neck cancers were worse for blacks, with some 20 percent fewer blacks surviving past five years than caucasians. Three out of 10 individuals of either race had both a TP53 mutation and PAX5 methylation do not survive as long as individuals who have had head and neck cancer and just a TP53 mutation. Survival after five years were two and a half times worse for blacks with PAX5 methylation than caucasians. The researchers also report that these related molecular alterations were dependent on where the original tumor began.
Researchers where able to decode and then validate the cancer genetic profiles of all participants. These patients mostly came from the Baltimore area. Their profiles were compared with information from 279 squamous cell carcinoma tissue samples in the Cancer Genome Atlas. Guerrero-Preston notes, more information is needed in terms of the genetic and epigenetic alterations before precise survival numbers can be known. He believes this will require 200 more volunteers. At this point, he plans on continuing his genetic analyses in blacks and plans on looking at the Latino population as well.
Photo from cancer.gov.