Association analysis of the ephrin-B2 gene in African-Americans with end-stage renal disease.

BACKGROUND: Genome scans in African-Americans with end-stage renal disease (ESRD) identified linkage on chromosome 13q33 in the region containing the ephrin-B2 ligand (EFNB2) genes. Interactions between the ephrin-B2 receptor and ephrin-B2 ligand play essential roles in renal angiogenesis, blood vessel maturation, and kidney disease. METHODS: The EFNB2 gene was evaluated as a positional candidate for non-diabetic and diabetic ESRD susceptibility in 1,071 unrelated African-American subjects; 316 with non-diabetic etiologies of ESRD, 394 with type 2 diabetes-associated ESRD and 361 healthy controls. Single nucleotide polymorphism (SNP) genotyping was performed on the Sequenom Mass Array System. Statistical analyses were computed using Dandelion version 1.26, Snpaddmix version 1.4 and Haploview version 3.32. RESULTS: Twenty-eight HapMap tag SNPs were genotyped spanning the 39 kilobases (kb) of the EFNB2 coding region, with average spacing of 1.43 kb. Analysis of 710 ESRD patient samples and 361 controls provided no evidence of single SNP associations in either diabetic or non-diabetic ESRD; although nominal evidence of association with all-cause ESRD was observed with a two SNP (p = 0.022) and three SNP (p = 0.023) haplotype, both containing SNPs rs7490924 and rs2391335 in intron 1. CONCLUSIONS: Although an attractive positional candidate gene, polymorphisms in the EFNB2 gene do not appear to contribute in a substantial way to non-diabetic, diabetic or all-cause ESRD susceptibility in African-Americans. Additional genes within the chromosome 13q33 linkage interval are likely contributors to African-American non-diabetic ESRD.

Participation in surgical oncology clinical trials: gender-, race/ethnicity-, and age-based disparities.

OBJECTIVE: To characterize the representation of racial/ethnic minorities, women, and older persons among participants in surgical trials sponsored by the National Cancer Institute (NCI). METHODS: The NCI Clinical Trial Cooperative Group surgical oncology trials database was queried for breast, colorectal, lung, and prostate cancers treated during the period 2000-2002 (n=13,991). Data from the SEER program and the Census were used to estimate age-, gender-, and race/ethnicity-specific incidence of the same cancers among U.S. adults during the same period. Enrollment fraction (EF), defined as the number of trial enrollees divided by the estimated U.S. cancer cases in each demographic group, was the primary outcome measure. Logistic regression was used to compare the enrollment of racial/ethnic, gender and age subgroups in this analysis. RESULTS: Relative to white patients (EF=0.72%), lower EFs were noted in African-American (0.48%, odds ratio [OR] vs whites 0.67, P<0.001), Hispanic (0.54%, OR 0.76, P<0.001), and Asian/Pacific islander (0.59%, OR 0.82, P=0.001) patients. Overall, women were more likely to enroll in surgical trials (1.12%) than men (0.22%, OR 5.06, P<0.001). Patients 65-74 years of age (EF 0.45%) were less likely to be enrolled than those 20-44 years of age (EF=2.28%, OR 0.20, P=0.001). CONCLUSIONS: The enrollment in surgical oncology trials is very low across all demographics. However, racial/ethnic minorities and older persons are less likely to be enrolled in cooperative group surgical oncology trials than are whites and younger patients. The high EF for women is due to the high availability of trials for women with breast cancer. Strategies to increase accrual to surgical trials and ameliorate disparities related to race/ethnicity, gender, and age are needed.