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 IVSI-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 IVSI-27A and prostate cancer risk supports a population-specific effect of susceptibility alleles in prostate tumorigenesis.