NCI Studies Examine Racial Disparity in Survival Among Patients With Endometrial Cancer

Researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, report findings that suggest a biological disparity for endometrial cancer exists between Caucasians and African Americans. The research was done in conjunction with Walter Reed Army Medical Center and other institutions. Two separate studies, one examining patient outcomes in four endometrial cancer clinical trials¹, and the other looking at gene expression patterns in endometrial tumors², provide evidence that biological factors can contribute to the significant racial disparity in survival rates for this cancer. Both studies will be presented at the Society of Gynecologic Oncologists (SGO) 2005 Annual Meeting on Women’s Cancer, March 19-23, 2005, in Miami, Fla., and will be published later this year.

It is estimated that in 2005 there will be approximately 40,000 new cases of cancer of the endometrium, or lining of the uterus, and about 7,000 endometrial cancer-related deaths. While the rate for new cancers in African-American women is lower than for Caucasians, African-American women have a greater mortality rate from endometrial cancer than Caucasians; an NCI 1989-1994 review reported that 5-year survival for endometrial cancer was 86 percent in Caucasians but only 54 percent in African Americans.

“The etiology underlying this disparity is multi-fold,” said LTC Larry Maxwell, M.D., of Walter Reed’s Department of Obstetrics and Gynecology and NCI, an author of both studies. “It can include cultural differences in dealing with medical illness and unequal access to the proper care and therapy, but could also arise from a difference in biology which may result in more aggressive tumors in some populations.”

Maxwell and his group sought to uncover the role of biology by examining survival outcome in a setting that should provide equal treatment to all patients: a clinical trial. The researchers studied data from four trials performed by the Gynecologic Oncology Group (GOG), an NCI-funded cooperative group that coordinates most of the large therapeutic gynecologic cancer studies in the United States. The survival rates for 168 African-American patients and 997 Caucasian patients with Stage III, Stage IV or recurrent endometrial cancer were compared. The analysis showed that African-American women with endometrial cancer have a 25 percent greater chance of dying than Caucasian women with the same diagnosis, and the overall median survival for African-American patients was 10.6 months compared to 12.2 months for Caucasians.

In the second study, the investigators evaluated global gene expression among endometrial cancer patients to determine any specific differences that may account for a biological disparity. Tumors from 18 African-American patients and 27 Caucasian patients were matched and compared according to stage, tumor grade, and cell type. In the initial analysis, Maxwell and his group could not identify expression profiles unique to each race. However, when they excluded early-stage cancers and focused only on advanced stage cancers, they observed expression profiles that did cluster according to race; 325 total transcripts had different expression levels in African Americans and Caucasians.

“Both of these studies suggest that underlying molecular differences may partially explain the disparity in survival outcome for endometrial cancer for these two groups,” said Maxwell. He added that the studies do not imply that African Americans and Caucasians are genetically different, but rather that multiple factors including environment and culture may result in a difference in gene expression. “Further research is needed to determine how these differences can be used to help identify better therapies for high-risk minority groups.”

“Though this study looks at one particular cancer in terms of racial disparities, we hope that it may shed light on our broader work in this area,” said Harold Freeman, M.D., director of the NCI Center to Reduce Cancer Health Disparities.

1 “Racial disparity among patients with advanced/recurrent endometrial adenocarcinomas: a Gynecologic Oncology Group (GOG) study.” G. Larry Maxwell, Chunquio Tian, John I. Risinger, Carol Brown, Wendy Brewster.

2 “Racial disparity in global gene expression among patients with advanced endometrial adenocarcinoma.” G. Larry Maxwell, G.V.R. Chandramouli, Lou Dainty, Tracy Litzi, Michael A. Bidus, Andrew Berchuck, Carl J. Barrett, John I. Risinger.

Tim Bonfield, Cincinnati Enquirer, April 6, 2005

A gene mutation developed generations ago to protect West African people against malaria may help explain why modern African-American men are more likely to develop prostate cancer and die from it than white men, according to a study led by University of Cincinnati researchers.

The mutation, which affects how the body develops tumors, is found in about 70 percent of African-Americans, according to Dr. Alex Lentsch, a researcher with UC’s surgery department. The study was presented Tuesday at the Experimental Biology 2005 conference in San Diego.

The mutation blocks a red blood cell receptor known as the Duffy antigen receptor for chemokines. Chemokines are small proteins that can help tumors grow by promoting blood vessel growth.

In mice, when the receptor is genetically “knocked out,” chemokines remain active at forming new blood vessels, allowing tumors to grow faster. The same kind of “knockout” happened naturally in West African men as a result of the anti-malarial mutation, the study says.

“Our research shows that prostate cancer could grow more aggressively in men who have the mutated gene,” Lentsch said. “We think this is an important first step to understanding why African-American men have a 60 percent higher prevalence of prostate cancer and double the mortality compared with white men.”

Prostate cancer is the No. 2 cause of cancer death (after lung cancer) in African-American men in Ohio, according to a 2003 state health report.

More than 800 black men per year develop prostate cancer statewide, and more than 200 per year die of it.

Dwight Tillery, executive director of UC’s Closing the Gap program on reducing racial disparities in health care, praised the findings.

“If heredity is a major culprit, then hopefully, this (study) will lead us to a remedy,” Tillery said.