Characterization of germline copy number variation in high-risk African American families with prostate cancer.
BACKGROUND
Prostate cancer is a complex multi-allelic disease and the most common malignancy in men. The incidence of prostate cancer in African American men is more than twice as high as that of any other race. Despite the high prevalence of prostate cancer amongst African American men, this population has been under represented in genetic studies of prostate cancer. Although genomic copy number variations (CNVs) have been detected in prostate tumors, this is the first study describing germline CNVs in African American hereditary prostate cancer families.


METHODS
Ten high-risk African American families with three or more affected individuals and with an early age of onset were recruited. From these families, 37 individuals, including 23 affected males, and 14 unaffected males, were selected for CNV analysis. Array comparative genomic hybridization was used to characterize germline CNVs unique to African American men with hereditary prostate cancer.


RESULTS
Through common aberration analysis in affected family members; novel CNVs were identified at chromosomes 1p36.13 and 16q23.3. Differential analysis comparing affected and unaffected family members identified 9.4 kb duplication on chromosome 14q32.33 which segregate with prostate cancer patients in these high-risk families.


CONCLUSIONS
The duplication at 14q32.33 encompasses IGHG3 gene which has been shown to have both significant gains in copy number as well as overexpression in prostate tumors in African Americans. These CNVs may represent a component of genetic predisposition which contributes to the high prevalence and mortality of prostate cancer in African American men.
Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
Elisa M
EM
Ledet
Xiaofeng
X
Hu
Oliver
O
Sartor
Walter
W
Rayford
Marilyn
M
Li
Diptasri
D
Mandal
D001741:Black or African American / Q000235:genetics* / Q000706:statistics & numerical data*; D000368:Aged; D000818:Animals; D002878:Chromosomes, Human, Pair 1; D002883:Chromosomes, Human, Pair 14; D002885:Chromosomes, Human, Pair 16; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics*; D005192:Family Health; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011471:Prostatic Neoplasms / Q000208:ethnology* / Q000235:genetics*; D012307:Risk Factors; D014481:United States / Q000453:epidemiology