Dataset Information

Hereditary prostate cancer in African American families: linkage analysis using markers that map to five candidate susceptibility loci.

ABSTRACT: African American men have the highest incidence of prostate cancer in the world. Despite this statistic, linkage studies designed to localise prostate cancer susceptibility alleles have included primarily men of Caucasian descent. In this report, we performed a linkage analysis using 33 African American prostate cancer families from two independent research groups. In total, 126 individuals (including 89 men with prostate cancer) were genotyped using markers that map to five prostate cancer susceptibility loci, namely HPC1 at 1q24-25, PCAP at 1q42.2-43, CAPB at 1p36, HPC20 on chromosome 20, and HPCX at Xq27-28. Multipoint mode-of-inheritance-free linkage analyses were performed using the GENEHUNTER software. Some evidence of prostate cancer was detected to HPC1 using all families with a maximum NPL Z score of 1.12 near marker D1S413 (P=0.13). Increased evidence of linkage was observed in the 24 families with prostate cancer diagnosis prior to age 65 years and in the 20 families with male-to-male transmission. Some evidence of prostate cancer linkage was also detected at markers mapping to PCAP, HPC20, and HPCX. Continued collection and analysis of African American prostate cancer families will lead to an improved understanding of inherited susceptibility in this high-risk group.

SUBMITTER: Brown WM

PROVIDER: S-EPMC2410149 | biostudies-literature | 2004 Jan

REPOSITORIES: biostudies-literature

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Hereditary prostate cancer in African American families: linkage analysis using markers that map to five candidate susceptibility loci.

Brown W M WM Lange E M EM Chen H H Zheng S L SL Chang B B Wiley K E KE Isaacs S D SD Walsh P C PC Isaacs W B WB Xu J J Cooney K A KA

British journal of cancer 20040101 2

African American men have the highest incidence of prostate cancer in the world. Despite this statistic, linkage studies designed to localise prostate cancer susceptibility alleles have included primarily men of Caucasian descent. In this report, we performed a linkage analysis using 33 African American prostate cancer families from two independent research groups. In total, 126 individuals (including 89 men with prostate cancer) were genotyped using markers that map to five prostate cancer susc ...[more]

PMID: 14735201

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Project description:BackgroundThe inability of aspirin (ASA) to adequately suppress platelet aggregation is associated with future risk of coronary artery disease (CAD). Heritability studies of agonist-induced platelet function phenotypes suggest that genetic variation may be responsible for ASA responsiveness. In this study, we leverage independent information from genome-wide linkage and association data to determine loci controlling platelet phenotypes before and after treatment with ASA.MethodsClinical data on 37 agonist-induced platelet function phenotypes were evaluated before and after a 2-week trial of ASA (81 mg/day) in 1231 European American and 846 African American healthy subjects with a family history of premature CAD. Principal component analysis was performed to minimize the number of independent factors underlying the covariance of these various phenotypes. Multi-point sib-pair based linkage analysis was performed using a microsatellite marker set, and single-SNP association tests were performed using markers from the Illumina 1 M genotyping chip from deCODE Genetics, Inc. All analyses were performed separately within each ethnic group.ResultsSeveral genomic regions appear to be linked to ASA response factors: a 10 cM region in African Americans on chromosome 5q11.2 had several STRs with suggestive (p-value < 7 x 10-4) and significant (p-value < 2 x 10-5) linkage to post aspirin platelet response to ADP, and ten additional factors had suggestive evidence for linkage (p-value < 7 x 10-4) to thirteen genomic regions. All but one of these factors were aspirin response variables. While the strength of genome-wide SNP association signals for factors showing evidence for linkage is limited, especially at the strict thresholds of genome-wide criteria (N = 9 SNPs for 11 factors), more signals were considered significant when the association signal was weighted by evidence for linkage (N = 30 SNPs).ConclusionsOur study supports the hypothesis that platelet phenotypes in response to ASA likely have genetic control and the combined approach of linkage and association offers an alternative approach to prioritizing regions of interest for subsequent follow-up.

Dataset Information

Hereditary prostate cancer in African American families: linkage analysis using markers that map to five candidate susceptibility loci.

Publications

Hereditary prostate cancer in African American families: linkage analysis using markers that map to five candidate susceptibility loci.

Similar Datasets

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