Chromosome 8q24 risk variants in hereditary and non-hereditary prostate cancer patients.
BACKGROUND
Multiple variants in three regions at 8q24 are consistently found to be associated with prostate cancer (PCa) risk in population-based association studies. The role that these variants may play in familial prostate cancer risk has not been extensively investigated.


METHODS
We evaluated 12 SNPs at three 8q24 regions using population-based association and family-based linkage and association methods in hereditary PCa (HPC) probands and their families, non-HPC patients, and unaffected screened controls, all recruited at Johns Hopkins Hospital.


RESULTS
For multiple variants in Region 1 (e.g., rs1447295) and Region 2 (e.g., rs16901979), we found statistically significantly higher frequencies of previously identified risk alleles and genotypes in HPC probands than in unaffected controls. Furthermore, in Region 2 the risk alleles were statistically significantly more frequent in HPC probands than in non-HPC patients. Family-based transmission tests found risk alleles of SNPs in Region 2, but not in Regions 1 and 3, were significantly over-transmitted to affected men in these families. We found little evidence supporting PCa linkage at 8q24 in 168 HPC families, in part explained by the observation of multiple, different risk allele-containing haplotypes segregating in the vast majority of these families.


CONCLUSIONS
Our study further supports the presence of PCa susceptibility loci at 8q24, particular at Region 2, and also provides evidence that these SNPs play an important role in familial prostate cancer. Large family-based studies are needed to confirm our novel findings.
Sun
Jielin
J
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Lange
Ethan M
EM
Isaacs
Sarah D
SD
Liu
Wennuan
W
Wiley
Kathleen E
KE
Lange
Leslie
L
Gronberg
Henrik
H
Duggan
David
D
Carpten
John D
JD
Walsh
Patrick C
PC
Xu
Jianfeng
J
Chang
Bao-Li
BL
Isaacs
William B
WB
Zheng
S Lilly
SL
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics*; D012307:Risk Factors