Association of hereditary prostate cancer gene polymorphic variants with sporadic aggressive prostate carcinoma.
BACKGROUND
ELAC2, MSR1, and RNASEL are candidate genes for hereditary prostate carcinoma (HPC). While, studies have demonstrated that single nucleotide polymorphisms (SNPs) in these genes are associated with sporadic disease as well as HPC, these results are often not replicated in follow-up studies. Given that the majority of patients studied had localized disease and up to 50% of localized prostate cancer is clinically insignificant, the inability to replicate the initial findings may reflect that some subjects had indolent tumors. Herein, we examine patients with metastatic disease to determine if an association exists between HPC SNPs and unambiguously significant prostate cancer.


METHODS
We examined polymorphisms within ELAC2 (S217L, A541T, E622V), MSR1 (P275A, R293X, aIVS5-59c), and RNASEL (E265X, R462Q, D541E) in 150 European-Americans with metastatic prostate cancer and 170 prostate cancer-free controls using pyrosequencing assays.


RESULTS
Only ELAC2 217L (37% cases vs. 29% controls (P=0.034)) and RNASEL 541E (61% cases vs. 53% controls (P=0.045)) were over-represented. Analysis of genotypes revealed that presence of the leucine ELAC2 allele (OR 1.54: 95% CI=0.99-2.41, SS vs. SL, LL) and homozygosity for the glutamic acid RNASEL allele (OR 1.68: 95% CI=1.04-2.70, EE vs. DE, DD) were associated with increased risk. Patients with both genotypes were of particularly high-risk (OR 2.66: 95% CI=1.36-5.19).


CONCLUSIONS
These results suggest that, in a European-American population, ELAC2 217L and RNASEL 541E are associated with metastatic sporadic disease. ELAC2 and RNASEL SNP analysis may prove useful in determining which patients are at risk for developing clinically significant prostate carcinoma.
Noonan-Wheeler
Ferrin C
FC
Department of Surgery, Washington University School of Medicine, Barnes-Jewish Hospital, St. Louis, Missouri 63110, USA.
Wu
William
W
Roehl
Kimberly A
KA
Klim
Aleksandra
A
Haugen
John
J
Suarez
Brian K
BK
Kibel
Adam S
AS
D001483:Base Sequence; D017931:DNA Primers; D004722:Endoribonucleases / Q000235:genetics; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D051117:Scavenger Receptors, Class A / Q000235:genetics; D014481:United States; D044465:White People
D017931:DNA Primers; C421605:ELAC2 protein, human; C495139:MSR1 protein, human; D009363:Neoplasm Proteins; D051117:Scavenger Receptors, Class A; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease