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African American men were significantly more likely to have prostate cancer at needle biopsy than were white men in a study reported by Dr. William Dale.
In another study presented by Dr. Jerome Jean-Gilles Jr., researchers identified biologic differences that may help explain the disproportionately unfavorable outcome of prostate cancer in African Americans, compared with whites.
One of the most striking and unexpected findings in Dr. Dale's study was the high percentage of African Americans who said during postbiopsy interviews it was "impossible" that they could have prostate cancer.
Perceptions of disbelief about their diagnosis were expressed by about 55% of black men, compared with less than 20% of white men.
Yet the positive biopsy rate was 70% among 93 African Americans, compared with 50% among 96 whites referred after screening positive for possible prostate cancer, according to Dr. Dale and his colleagues at the University of Chicago.
In a multivariate analysis of predictors of higher estimated likelihood of cancer, there was a negative correlation with African American race and health status, and a positive correlation with age and cancer-specific anxiety.
Surprisingly, there was no correlation between the presence of symptoms, prostate-specific antigen (PSA) scores, education, and income.
African Americans in the study were more likely to have higher prebiopsy PSA levels (9.3 ng/mL vs. 7.5 ng/mL). The average age in both ethnic groups was 63 years.
Despite an emphasis on men being well-informed before undergoing prostate cancer screening, the findings could be explained by a lack of information at the time of biopsy and by a patient's desire to remain hopeful and avoid expressing concerns they feel could affect their outcomes, according to Dr. Dale.
The study was supported by the National Cancer Institute and the National Institute on Aging.
In the second study, researchers identified biologic differences between prostate cancer in African Americans compared with whites.
Array-based comparative genomic hybridization (array-CGH) was used to evaluate prostate tumor tissue in 40 men, both African American and white, who underwent radical prostatectomy for prostate cancer.
Array-CGH allows genome-wide mapping and provides a high-resolution look at targeted regions of the genome. It has been used to identify signaling and metabolic pathways associated with tumor progression, as well as to detect submicroscopic chromosomal deletions and duplications in patients with mental retardation and other disabilities.
Array-CGH identified 28 chromosomal alterations that were significantly different between African American and Caucasian men, Dr. Jean-Gilles said. In all, 11 regions were more commonly altered in African Americans than in whites. Those regions were 3q25-26, 3q28-29, 4p12-14, 4p13, 9q21, 10q11, 11q14, 12p13, 14q12, 16p11, and 20p11-20q11.
Hierarchical clustering of gene expression data from 19 African Americans and 14 Caucasians revealed two distinct clusters.
One cluster consisted of Caucasian patients and the other of African American patients, with 81% of African Americans in one cluster and 79% of Caucasians in the other.
"This shows that there are recurrent expression patterns in prostate tumors and that these patterns are different for African Americans and for Caucasians," said Dr. Jean-Gilles, who was a research fellow at New York University School of Medicine at the time of the study, and is now a resident at Brown University in Providence, R.I.
Of the 28 altered chromosomal regions, 27 were correlated with gene-expression changes. Gene ontology and pathway analyses also were conducted, revealing 16 pathways that were altered in both cohorts including apoptosis, cell cycle, and proteasome degradation.
There were, however, several pathways that were distinct to each cohort. Among Caucasians, five pathways showed altered gene expression: G1/S cell cycle, gonadotropin-releasing hormone signaling, histidine metabolism, integrin-mediated cell adhesion, and matrix metalloproteinase. Among African Americans, three distinct pathways displayed altered gene expression: cell adhesion, neutral endopeptidase, and ubiquitin-mediated proteolysis.
Dr. Jean-Gilles said that the pilot study is a proof of concept and that a larger sample size and higher-resolution arrays are needed to validate the findings. The study was led by Dr. Iman Osman, of New York University.
ASCO discussant Rick Kittles, Ph.D., of the University of Chicago, said one of the issues with studies that try to compare tumor tissue by race is the level of heterogeneity in both samples and patients. Some African Americans share a European background with Caucasian Americans, while prostate cancer itself is an extremely heterogeneous disease. Thus he questioned whether the changes observed reflect differential behavior of the disease or normal differences between African Americans and European Americans.
Dr. Kittles also noted that several recent studies have identified variants on chromosome 8q24 as a key genetic risk factor for prostate cancer, and that signal was not observed in the current study.
Dale W., et al. Perception of African American men of their likelihood of a cancer diagnosis at the time of prostate biopsy. Abstract 6503.
Jean-Gilles Jr. J., et al. Different chromosomal alterations correlate with gene expression in African American (AA) versus Caucasian American (CA) prostate cancer (PC) patients. Abstract 5000.
Commentary |
Despite the established fact that black men in general present with more advanced disease and have worse outcomes, debate has raged over whether similar men, treated similarly, have similar outcomes. Stated in other words: For a given age, prostate-specific antigen level, and digital rectal examination findings, are black and white men equally likely to have cancer and equally likely to have a poor outcome? Perhaps more important, how do the races perceive their vulnerability to cancer? The first abstract suggests that, despite black men being more likely to have cancer on biopsy, they view themselves as being at lower risk. Specifically, a study from the University of Chicago found that black men undergoing biopsy were significantly more likely to have cancer (70% vs. 44%, P less than .05). Despite being referred for biopsy, however, 58% of black men said that they had a 0% chance of having cancer (i.e. it was impossible). This compared with 25% among white men (P less than .01). Though this was a small study, if confirmed in future studies, the implications are important. Specifically, despite intensive efforts to educate black men about the risk of prostate cancer, this study would suggest those efforts are not translating into a greater knowledge about prostate cancer among black men. As such, these findings arouse concern; they imply that much more needs to be done to narrow the prostate cancer education gap between the races. Only once this gap is overcome, will we see the disparity in morbidity start to narrow. That black men on average present more commonly with advanced disease and have poorer outcomes than white men has long been known. While much of this may be attributable to socioeconomic factors, they are unlikely to explain the complete spectrum of observed racial disparity. Therefore, interest has been intense in identifying biological explanations. The second abstract suggests black and white men have genetic differences within tumors. Investigators from New York University and Memorial Sloan Kettering Cancer studied the genetics of 40 tumors from black and white men who underwent radical prostatectomy. Using the latest in genomic technology, the researchers identified several genetic areas that differed significantly by race. This led to the identification of several molecular pathways that may be differentially regulated within each race. While the findings are promising, the authors concluded that larger studies are needed to verify these results. Moreover, black men in the United States often share a significant genetic background with white men. As such, whether the results stem from true genetic differences inherent in the races, tumor differences, lifestyle differences, or some other factor remains unclear. It is hoped, however, that this type of research will continue to unravel the complexity of race and prostate cancer at the genetic level, with the ultimate goal of narrowing the gap in prostate cancer disparity. — Stephen J. Freedland, M.D.and Judd W. Moul, M.D.
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