Association between polymorphisms in cell cycle genes and advanced prostate carcinoma.
BACKGROUND
Single nucleotide polymorphisms (SNPs) have been associated with a variety of malignancies including prostate carcinoma (PCa). Since a high percentage of PCa patients have low risk disease, of particular interest is not whether SNPs are associated with localized PCa, but whether they are associated with aggressive, potentially lethal disease. Herein, we explored the role of SNPs in cell cycle genes to determine if they were associated with advanced PCa.


METHODS
Nine previously implicated SNPs in six cell cycle genes were evaluated in a European-American cohort of 186 patients with advanced PCa and 222 cancer-free controls. All patients received hormone ablation and had either a PSA>50 ng/ml or documented metastatic disease. Controls were all 75 years of age or older, had a negative DRE and had a PSA<4.0 ng/ml. All genotypes were determined using Pyrosequencing assays.


RESULTS
One of nine (CDKN1A c10791t) was statistically different (P<0.05) and an additional two of nine (CCND1 a870g and MDM2 tSNP309g) approached significance (P<0.1). Analysis of genotypes revealed that presence of at least one copy of the t allele of MDM2 tSNP309g was associated with an increased risk of advanced PCa (OR 2.26: 95% CI=1.15-4.46) which was particularly strong in androgen-independent disease (OR 2.28: 95% CI=1.01-5.12) and younger age of diagnosis (OR 2.61: 95% CI=1.05-6.46).


CONCLUSIONS
These results suggest that in a European-American population, SNPs within cell cycle genes are promising markers for aggressive PCa. Larger studies will be needed to confirm these findings.
Kibel
Adam S
AS
Department of Surgery, Washington University School of Medicine, Barnes-Jewish Hospital, St. Louis, Missouri 63110, USA. kibela@wustl.edu
Jin
Carol H
CH
Klim
Aleksandra
A
Luly
Jason
J
A Roehl
Kimberly
K
Wu
William S
WS
Suarez
Brian K
BK
D000368:Aged; D002277:Carcinoma / Q000453:epidemiology* / Q000235:genetics* / Q000556:secondary; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D018816:Genes, cdc; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors