Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men.
A whole-genome admixture scan in 1,597 African Americans identified a 3.8 Mb interval on chromosome 8q24 as significantly associated with susceptibility to prostate cancer [logarithm of odds (LOD) = 7.1]. The increased risk because of inheriting African ancestry is greater in men diagnosed before 72 years of age (P < 0.00032) and may contribute to the epidemiological observation that the higher risk for prostate cancer in African Americans is greatest in younger men (and attenuates with older age). The same region was recently identified through linkage analysis of prostate cancer, followed by fine-mapping. We strongly replicated this association (P < 4.2 x 10(-9)) but find that the previously described alleles do not explain more than a fraction of the admixture signal. Thus, admixture mapping indicates a major, still-unidentified risk gene for prostate cancer at 8q24, motivating intense work to find it.
Freedman
Matthew L
ML
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Haiman
Christopher A
CA
Patterson
Nick
N
McDonald
Gavin J
GJ
Tandon
Arti
A
Waliszewska
Alicja
A
Penney
Kathryn
K
Steen
Robert G
RG
Ardlie
Kristin
K
John
Esther M
EM
Oakley-Girvan
Ingrid
I
Whittemore
Alice S
AS
Cooney
Kathleen A
KA
Ingles
Sue A
SA
Altshuler
David
D
Henderson
Brian E
BE
Reich
David
D
D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000483:Alleles; D002874:Chromosome Mapping / Q000379:methods*; D002898:Chromosomes, Human, Pair 8; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors
D005819:Genetic Markers