Mutation screening and association study of the candidate prostate cancer susceptibility genes MSR1, PTEN, and KLF6.
BACKGROUND
MSR1, PTEN, and KLF6 have been implicated as candidate susceptibility genes for prostate tumorigenesis.


METHODS
Three hundred Jewish prostate cancer patients were screened for alterations in these genes.


RESULTS
MSR1 was conserved in all patients. PTEN screening revealed a novel missense mutation and a silent change. Five KLF6 alterations were detected in 17 patients, including Q160X, the only nonsense KLF6 germline mutation described to date in a cancer patient. The KLF6 IVS1-27G>A polymorphism, recently associated with prostate cancer risk, was detected in 11.9% of the patients and 17.3% of the controls (P = 0.043). IVS1-27A allele frequency was significantly lower in prostate cancer patients (P = 0.030), specifically in Ashkenazi patients (P = 0.047) compared to controls.


CONCLUSIONS
We found no evidence that MSR1 and PTEN germline mutations are associated with prostate cancer risk in Jews. The negative association between KLF6 IVS1-27A and prostate cancer risk supports a population-specific effect of susceptibility alleles in prostate tumorigenesis.
Bar-Shira
Anat
A
Genetic Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Matarasso
Noa
N
Rosner
Serena
S
Bercovich
Dani
D
Matzkin
Haim
H
Orr-Urtreger
Avi
A
D000328:Adult; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D007557:Israel; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000502:physiology; D010375:Pedigree; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D051117:Scavenger Receptors, Class A / Q000235:genetics* / Q000502:physiology
D004273:DNA, Neoplasm; C105465:KLF6 protein, human; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; C495139:MSR1 protein, human; D011518:Proto-Oncogene Proteins; D051117:Scavenger Receptors, Class A; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human