Featured Research

from universities, journals, and other organizations

Genetic mutations, molecular alterations may explain racial differences in head, neck cancers

Date:
December 8, 2013
Source:
Johns Hopkins Medicine
Summary:
A team of scientists has identified a handful of genetic mutations in black Americans, in addition to some chemical alterations affecting gene activity, which may help explain why the death rate among African-Americans from the most common form of head and neck cancer continues to hover some 18 percent higher above the death rate of whites with the same cancer.

A team of scientists at Johns Hopkins and in Texas has identified a handful of genetic mutations in black Americans, in addition to some chemical alterations affecting gene activity, which may help explain why the death rate among African-Americans from the most common form of head and neck cancer continues to hover some 18 percent higher above the death rate of whites with the same cancer.

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

The team's latest analysis of tumor tissue and blood samples from 60 black and 168 white men and women with the disease 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.

Researchers plan to present the study findings on Dec. 7 in Atlanta at the Sixth American Association for Cancer Research Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved. More than 30,000 Americans die annually from some form of head and neck squamous cell carcinoma.

According to lead study investigator and genomics epidemiologist Rafael Guerrero-Preston, Dr.P.H., his team's research findings represent what could be the final piece in the survival-gap mystery, adding to such well-studied and well-known contributing factors such as poor education, poverty, limited access to health care and untimely access to treatments.

"Our study results are essential to understanding and eventually remedying head and neck cancer survival disparities between races," says Guerrero-Preston, an assistant professor in otolaryngology -- head and neck surgery at the Johns Hopkins University School of Medicine and its 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."

Among the study's key findings were some 317 epigenetic modifications significantly more prevalent in people with head and neck cancers 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 head and neck cancers 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 their study, survival outcomes for all head and neck cancers were worse for blacks, with some 20 percent fewer blacks surviving past five years than whites.

Three out of 10 people of either race with head and neck cancer and both a TP53 mutation and PAX5 methylation do not live as long as people who have had head and neck cancer and just a TP53 mutation.

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

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

For cancers originating at the back of the mouth, or oropharynx, blacks had significantly more NOTCH1 mutations than whites, at 67 percent and 14 percent, respectively. Outside the oropharynx, however, the reverse occurred, with no blacks and 18 percent of whites having a NOTCH1 mutation. PAX1 and PAX5 epigenetic alterations were similarly reversed depending on tumor location, with PAX1 methylation in 52 percent of blacks and in 62 percent of whites in the oropharynx, compared to 70 percent and 60 percent, 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, a national database.

Guerrero-Preston says that further examination of the genetic and epigenetic modifications will be required before precise survival numbers, measured in months or years, can be ascribed to any particular genetic mutation or combination of changes. Such detailed findings, he says, will require some 200 additional study volunteers in order for the study to be scientifically accurate.

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

"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," says Guerrero-Preston.


Story Source:

The above story is based on materials provided by Johns Hopkins Medicine. Note: Materials may be edited for content and length.


Cite This Page:

Johns Hopkins Medicine. "Genetic mutations, molecular alterations may explain racial differences in head, neck cancers." ScienceDaily. ScienceDaily, 8 December 2013. <www.sciencedaily.com/releases/2013/12/131208090240.htm>.
Johns Hopkins Medicine. (2013, December 8). Genetic mutations, molecular alterations may explain racial differences in head, neck cancers. ScienceDaily. Retrieved September 17, 2014 from www.sciencedaily.com/releases/2013/12/131208090240.htm
Johns Hopkins Medicine. "Genetic mutations, molecular alterations may explain racial differences in head, neck cancers." ScienceDaily. www.sciencedaily.com/releases/2013/12/131208090240.htm (accessed September 17, 2014).

Share This



More Health & Medicine News

Wednesday, September 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

President To Send 3,000 Military Personnel To Fight Ebola

President To Send 3,000 Military Personnel To Fight Ebola

Newsy (Sep. 16, 2014) President Obama is expected to send 3,000 troops to West Africa as part of the effort to contain Ebola's spread. Video provided by Newsy
Powered by NewsLook.com
Man Floats for 31 Hours in Gulf Waters

Man Floats for 31 Hours in Gulf Waters

AP (Sep. 16, 2014) A Texas man is lucky to be alive after he and three others floated for more than a day in the Gulf of Mexico when their boat sank during a fishing trip. (Sept. 16) Video provided by AP
Powered by NewsLook.com
Ivorians Abandon Monkey Pets in Fear Over Ebola Virus

Ivorians Abandon Monkey Pets in Fear Over Ebola Virus

AFP (Sep. 16, 2014) Since the arrival of Ebola in Ivory Coast, Ivorians have been abandoning their pets, particularly monkeys, in the fear that they may transmit the virus. Duration: 00:47 Video provided by AFP
Powered by NewsLook.com
Study Links Male-Pattern Baldness To Prostate Cancer

Study Links Male-Pattern Baldness To Prostate Cancer

Newsy (Sep. 16, 2014) New findings suggest men with a certain type of baldness at age 45 are 39 percent more likely to develop aggressive prostate cancer. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

      Technology News



      Save/Print:
      Share:

      Free Subscriptions


      Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

      Get Social & Mobile


      Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

      Have Feedback?


      Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
      Mobile: iPhone Android Web
      Follow: Facebook Twitter Google+
      Subscribe: RSS Feeds Email Newsletters
      Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins