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Chromosome 8q24 risk variants in hereditary and non‐hereditary prostate cancer patients
Author(s) -
Sun Jielin,
Lange Ethan M.,
Isaacs Sarah D.,
Liu Wennuan,
Wiley Kathleen E.,
Lange Leslie,
Gronberg Henrik,
Duggan David,
Carpten John D.,
Walsh Patrick C.,
Xu Jianfeng,
Chang BaoLi,
Isaacs William B.,
Zheng S. Lilly
Publication year - 2008
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20695
Subject(s) - prostate cancer , proband , single nucleotide polymorphism , genetics , haplotype , allele , population , biology , cancer , oncology , medicine , genotype , mutation , gene , environmental health
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. Prostate 68: 489–497, 2008. © 2008 Wiley‐Liss, Inc.