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Racial genetic admixture linked to endometrial cancer outcomes


 

AT THE ANNUAL MEETING ON WOMEN'S CANCER

LOS ANGELES – Racial makeup based on genetic testing trumps self-reported race as a predictor of endometrial cancer outcomes, suggests the results of a study reported at the annual meeting of the Society of Gynecologic Oncology.

Researchers compared patient self reports of racial identity and the results of genotyping for markers of race in 217 women with endometrial cancer who had any-stage endometroid tumors.

The risk of cancer progression or death rose by 2% with each 1% increase in African racial genetic admixture and fell by 3% with each 1% increase in European racial genetic admixture.

"Racial genetic admixture significantly predicts the risk of recurrence and progression-free survival in endometrial cancer patients. Importantly, this risk is irrespective of self-designated race and could be used to stratify and identify patients’ recurrence risk," reported lead author Dr. Rodney P. Rocconi, a gynecologic oncologist at the Mitchell Cancer Institute and University of South Alabama in Mobile.

The results are worth examining as a key "to unraveling the etiology of this disparity, with the hopes of improving treatment outcomes and eventually eliminating this racial disparity in the future."

Dr. Rocconi acknowledged that the study included only endometroid tumors, and noted that black women typically have higher proportions of carcinosarcoma and type 2 endometrial cancers, a distinction that’s not always known preoperatively.

"In an ideal world, we would like to evaluate that (larger) population," Dr. Rocconi said. But "it came down to having enough funding to evaluate a population that is meaningful. In the future, by all means, it would be an extremely important population to look at."

African American women make up just 7% of all patients with endometrial cancer but account for 15% of deaths from the disease, he noted.

"To date, breaking down the definition of race in cancer racial disparity has largely been overlooked. Considering the majority of racial disparity research utilizes self-designated race, this in my opinion is the greatest limitation in this type of research. Self-designated race can be used as a proxy, but it is not precise in measurement of population differences. It cannot infer genetic similarity," he said.

Genetic testing "can mathematically calculate the place of origin genetically. Thus, it’s a more precise definition of race, and this methodology is important in teasing out those true factors of racial disparity. Simply put, this definition allows a continuous variable, a true percentage of African descent, as opposed to a categorical value of self-designated African American [race]," he said.

For the study, Dr. Rocconi and his coinvestigators identified women from Gynecologic Oncology Group (GOG) trial 210 who had endometroid tumors.

The team extracted DNA from tumor-free tissue samples and performed genotyping for 140 ancestry informative markers (AIMs), or single-nucleotide polymorphisms that occur in different frequencies in populations from different world geographic regions.

The 5-year rate of progression-free survival was 82% among self-reported white women and 74% among self-reported African American women, Dr. Rocconi reported.

Mean racial genetic admixture scores showed considerable racial genetic heterogeneity among both self-reported African American women (65% African, 20% European, and 15% Native American Indian) and self-reported white women (77% European, 17% Native American Indian, and 6% African).

After adjustment for self-reported race, women’s risk of progression or death rose significantly with each 1% increase in African racial genetic admixture (hazard ratio, 1.02) and fell significantly with each 1% increase in European racial genetic admixture (HR, 0.97).

When women were stratified into quintiles of African racial genetic admixture, the risk of events rose steadily with quintile. Relative to their peers having 0%-2% of this racial genetic composition, women having 72%-86% were 7.7 times more likely to experience progression or death.

"For a reference, this is higher than any of the factors we take into account on a daily basis when stratifying high- or intermediate-risk endometrial cancer for recurrence," noted Dr. Rocconi, who disclosed that the study was sponsored by Amgen through a Young Investigator Award.

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