Replication Of Prostate Cancer Risk Loci In A Japanese Case-Control Association Study

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Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Cancer / Oncology
Article Date: 27 Oct 2009 - 0:00 PDT

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Genome-wide association studies can identify genetic allele variants of low penetrance that are strongly associated with cancer. This has been reported for prostate cancer (CaP) in a cohort of men with European ancestry. In the online edition of the Journal of the National Cancer Institute, Dr. Yamada and associates evaluate the association of 23 risk single-nucleotide polymorphisms (SNPs) and clinical characteristics with CaP in a cohort of Japanese men. The importance is to determine how cancer risks are genetically influenced in different ethnic populations.

DNA samples were obtained form 311 Japanese patients diagnosed with CaP between 2004 and 2006, 1,035 control men of Japanese ancestry undergoing health screening and 68 men without CaP. A total of 23 SNPs were selected for PCR and mass spectrometry on a genotyping platform.

For case patients the mean age was 66.7 years, the median PSA was 9.1ng/ml and 81% had Gleason score 7 or less. The 23 SNPs represented 17 distinct loci and nine SNPs were mapped to 10q, two SNPs each to 11q and 17q, and one each to 2p, 3p, 6q, 7q, 19q, and Xp. Seven known SNPs previously identified at 8q24, 17q12, and 3p12 were associated with CaP risk. Fifteen SNPs did not achieve significance. Only one of the two reported SNPs at 17q12 was associated with CaP risk in Japanese men. The five SNPs associated with CaP risk were evaluated for association with three specific clinical characteristics: Gleason score, tumor aggressiveness and patient age at diagnosis. No association was found with Gleason score or tumor aggressiveness, but two SNPs were associated with age younger than 66 years.

Overall, men with six or more risk alleles (27% of case men and 11% of control men) had a 6-fold increased risk of developing CaP compared with men who carried two or less of the risk alleles. Combining total number of risk alleles with Gleason score or CaP aggressiveness was not statistically significant. Men who carried 6 or more risk alleles (compared with men who carried 2 or less) had an increased risk of developing CaP at a younger age with a decrease in age at diagnosis by 0.68 years for each additional risk allele. Thus, risk alleles differed in Japanese men compared with European men and show the importance of validating genomic variants in different patient populations.

J Natl Cancer Inst. 2009 Sep 2. [Epub ahead of print]

Written by Christopher P. Evans, M.D.

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