Abstract
Prostate cancer (PCa) remains the most common male specific cancer worldwide as well as the second leading cause of cancer death in industrial countries. The incidence of PCa is expected to increase because of the increase in the ageing population. Multiple epidemiological studies have confirmed that PCa occurs at a higher prevalence and with a greater mortality rate in African American (AA) men than in other populations in the United States. The African American Hereditary Prostate Cancer Study (AAHPC) was initiated to recruit African American families into a hereditary prostate cancer study with the goal of undertaking genomic analysis to aid in identification of genetic factors in African Americans, which may in part explain the increased incidence and/or mortality from PCa in this population.
We previously performed a genomic scan and genetic linkage analysis on 77 AAHPC families to show the evidence for the segregation of potentially important HPC susceptibility loci. All 77 families had at least three cases and three unaffected family members providing blood specimens for the linkage study. These pedigrees were also classified by the mode of transmission into ‘no-male-to-male (NMM)’ and ‘male-to-male (MM)’ families. The NMM families show no evidence of potential male-to-male transmission of PCa and are thus useful for Chromosome X linkage analysis. Parametric and nonparametric linkage analysis using GENEHUNTER and GENEHUNTER-PLUS programs in addition to Ordered Subset Analysis (OSA) and linear nonparametric allele sharing methods using ASM showed peaks at 11q22, 17p11 and Xq21. We repeated the chromosome X analyses using the 29 NMM families, and the LOD score at Xq21 increased. Linkage analysis of the 16 families with > 6 affected members revealed two candidate regions at 2p21 (D2S2259) and 22q12 (D22S280) which had not been observed in the 77 families. A finemapping study using the same 77 families in the 17p region confirmed the peak, with one family having genome-wide significance in this region. Hence more study is warranted in this region and further finemapping and sequencing studies are planned.
Second AACR International Conference on the Science of Cancer Health Disparities— Feb 3–6, 2009; Carefree, AZ