Washington D.C. -- Faulty cell cycle "checkpoints" that fail to respondto DNA damage effectively may contribute to the high incidence of lungcancer in African-Americans, say researchers at Georgetown University'sLombardi Comprehensive Cancer Center and the National Cancer Institute(NCI).
Their study, reported in the October 15 issue of Cancer Research, isthe first epidemiological study to show the association of lung cancerrisk in African-Americans and efficiency of the critical "G2/Mcheckpoint." While the researchers report that this checkpoint wasgenerally less effective in the group of African-American lung cancerpatients they studied, they found this risk to be especially high inAfrican-American women and nearly a five-fold increase in lung cancerrisk in women with faulty G2-M checkpoint compared to women withefficient G2-M checkpoint. The study did not found any association ofthis checkpoint with lung cancer risk in whites.
"Although the study has limitations, our findings suggest onepossible explanation for the higher incidence of lung cancer in AfricanAmericans, who as a group smoke less than whites, yet still developmore lung cancer at comparatively younger ages," said the study's leadauthor, Yun-Ling Zheng, M.D., Ph.D., an assistant professor in theDepartment of Oncology at the Lombardi Comprehensive Cancer Center.
"Epidemiologists have long known that cancers are expressed at varyingrates in different racial groups, but we are only now able to useadvanced research techniques to look at the molecular reasons for thesedisparities," Zheng said. "The value of such research is that it canprovide new tools for risk calculation."
According to a 2002 report by the Surveillance, Epidemiology, and EndResults (SEER), the incidence of lung cancer in African-American menwas 42 percent higher compared with the incidence in white men, and therisk of lung cancer for African-American women was 13 percent higher.
Cell cycle checkpoints are mechanisms that regulate progression throughthe cell cycle of growth and division, ensuring that each step takesplace only once and in the right sequence. This study looked at theG2/M checkpoint, a specific point in the cell cycle that determines ifthe cell should temporarily halt its march toward division, allowingmore time for the damage to be repaired.
This checkpoint can be activated if a cell's genetic material isdamaged or if mistakes were made when DNA was replicated. A lessefficient checkpoint, however, would not catch and repair all DNAabnormalities, which could lead to genetic instability and thedevelopment of cancer, Zheng said.
To conduct the study, Zheng and her colleagues at the National CancerInstitute collected information as well as blood samples from 216patients with lung cancer and from 340 cancer-free control participantsfrom the Baltimore, Maryland area.
They then cultured the white blood cells, exposed them to gammaradiation, which inflicts genetic damage, and then they evaluated thecell cycle checkpoint. After adjusting for age, gender and a patient'shistory of smoking, the researchers found that a lower level ofradiation-induced G2/M arrest was associated with an increased risk oflung cancer among African-Americans.
The senior author of the study was Curtis C. Harris, M.D., of theLaboratory of Human Carcinogenesis, at the NCI, which also funded theresearch. Other co-authors include Zhipeng Yu, B.S., of the NCI;Christopher Loffredo, Ph.D. and Peter Shields, M.D., of GeorgetownUniversity Medical Center; Anthony Alberg, Ph.D., and Rex Yung, M.D.,of Johns Hopkins Medical Institutions; and Raymond Jones, Ph.D., DonnaPerlmutter M.S., and Mark Krasna, M.D., of the University of MarylandSchool of Medicine.
The Lombardi Comprehensive Cancer Center, part of Georgetown UniversityMedical Center and Georgetown University Hospital, seeks to improve thediagnosis, treatment and prevention of cancer through innovative basicand clinical research, patient care, community education and outreach,and the training of cancer specialists of the future. Lombardi is oneof only 39 comprehensive cancer centers in the nation, as designated bythe National Cancer Institute, and the only one in the Washington DCarea. For more information, go to http://lombardi.georgetown.edu/
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