Sunday, March 24, 2013
Disease progression and hazard for recurrence of endometrial cancer are significantly worse in patients with the highest degree of African genetic ancestry
For every 10% increase in a patient's African racial genetic admixture, risk of disease progression increased by a hazard ratio of 1.27 according to Rodney Rocconi, MD, of the University of South Alabama in Mobile, and colleagues. Study participants in the highest quartile of African racial genetic admixture had a significant and nearly eight-fold risk of recurrence, Rocconi said. Rocconi noted that African-American patients are disproportionately more likely to die of endometrial cancer: They make up 7% of endometrial cancer diagnoses, but account for 15% of all deaths. He added that they are "60% to 80% more likely to die from endometrial cancer" than other populations, even within data from randomized, controlled trials. One major limitation in studying genetic factors of race is the way individuals define race. Many participants have self-defined race, but factors associated with genetics relate to continent or continents of origin, which the researchers referred to as a person's admixture. The authors evaluated the association of racial genetic admixture with endometrial cancer recurrence and progression-free survival (PFS) in case-cohort study of 217 endometrial cancer patients (stage I-IV) with endometrioid histology. Participants were stratified by self-declared race (African American or white) and disease stage. Researchers sampled patients' tumors and tumor-free DNA to evaluate participants' ancestral genetic makeup and estimate racial genetic admixture. The sample consisted of 81 self-declared African Americans and 136 self-declared white participants. Based on self-declared race, there was no significant difference between groups in PFS. When participants were evaluated based on racial genetic admixture, each 1% of African ancestry was significantly associated with a 2.4% increase in risk of disease progression and a 27% hazard increase with every 10% of African ancestry. Participants had a positive protective association with European racial genetic admixture, with a 2.5% increase in hazard for PFS for every 1% genetic admixture and a 23% increase in hazard for PFS for every 10%. By quintile of racial genetic admixture among African-American participants, those in the highest quintile - 72% to 86% - had a nearly eight-fold risk of disease progression. Increasing quintiles of African-American genetic heritage were associated with higher risks of disease progression, though these associations were not significant, which Rocconi noted may be due to the low sample size per quintile. These genetic factors were significantly predictive of "risk of recurrence and PFS in endometrial cancer patients" and that these hazards existed "irrespective of self-designated race." Rocconi noted that further study of genetic definitions of race were important to better understand sources of disparity and improved outcomes in cancer patients.