Gene mutations may play a pivotal role in why African-Americans are more likely to die from smoking-related cancers than whites, Wake Forest Baptist Medical Center researchers said Monday.
Researchers conducted a clinical trial on 431 cancer patients from March 2015 to May 2016. The findings are published online in the journal Theranostics.
The majority of patients had advanced tobacco-related cancers — lung, colorectal and bladder. Of those, 13.5 percent were black.
Researchers found the black patients had an increased mutation rate in several genes, including the one most well-known for tobacco-related tumors, TP53.
“We know TP53 mutation happens in 55 percent of all cancer patients,” said Wei Zhang, the study’s lead author and the Hanes and Willis Family Professor in Cancer at Wake Forest School of Medicine. “In our study, we found that the African-American population had close to a 70 percent mutation rate. This data suggests that increases in TP53 mutation in African-Americans may be responsible for the observed resistance to chemotherapy and a poorer prognosis overall.”
Wake Forest Baptist researchers said tumors from study participants were sequenced to identify mutations and genetic alterations associated with smoking and/or black ancestry.
Researchers also found that a number of genes — including those that repair DNA damage and remodel chromatin — mutated at higher frequencies in black patients with cancer.
Additionally, they identified other genes that were highly mutated in current and former smokers, regardless of race.
“These results provide strong evidence that genomic instability is a fundamental hallmark of cancer and the events underlying the regulation of genome stability are centered on interactions with environmental factors and lifestyle, such as smoking,” Zhang said.
The study was posted three days after the U.S. Food and Drug Administration revealed its latest regulatory proposals that focus on the limiting, if not elimination, of menthol as a traditional cigarette flavoring.
Menthol styles, which are mint-flavored, have proven controversial for decades because they are considered a smoother way to smoke traditional cigarettes, and because manufacturers have been accused of specifically marketing them to minority consumers.
In 2009, Congress exempted menthol from banned flavorings in traditional cigarettes in the federal Tobacco Control Act.
FDA Commissioner Scott Gottlieb said the agency believes menthol in traditional cigarettes, and candy and fruit flavorings in e-cigarettes and vaporizers, are used to entice underage youth to tobacco products.
Advocates and public-health officials argue that without menthol, many smokers would choose not to smoke a tobacco-flavored product and quit.
Menthol’s popularity with smokers led Reynolds American Inc. to spend $29.25 billion in June 2015 to acquire Newport from Lorillard Inc. of Greensboro. Reynolds, now fully owned by British American Tobacco PLC, holds 56 percent of the U.S. menthol cigarette market share.
“It is important to better understand and treat cancers and other diseases caused by cigarette smoking,” said David Sweanor, an adjunct law professor at the University of Ottawa and the author of several electronic-cigarette studies. “It is great to see research that helps us better understand cigarette-caused disease and hopefully helps in the discovery of treatments.
“At the same time, this underscores the need for policy changes that remove unnecessary risks for anyone using nicotine,” Sweanor. “We are learning how some already-disadvantaged populations are at much greater risk.”
Zhang cautioned that the study’s findings need further validation in a larger trial.
“These exciting findings uncover new genetic information related to smoking that may lead to the development of novel diagnostic and therapeutic options for patients,” said the study’s co-corresponding author, Dr. Boris Pasche, the director of the medical center’s Comprehensive Cancer Center.