The rate of RNASEL 471delAAAG mutation was previously reported to be less than 7% in Ashkenazi prostate cancer patients. It seems plausible that the same mutation may also be involved in breast/ovarian cancer predisposition in Jewish individuals. To evaluate the role of this mutation in cancer predisposition, a total of 1011 individuals including 294 Jewish men with prostate cancer, 61 Ashkenazi women with ovarian cancer and 50 unaffected women, matched for age and ethnicity, were genotyped for sequence anomalies in a single RNASEL gene amplicon using DGGE and sequencing. Additionally, 209 Ashkenazi BRCA1/2 mutation carriers, 205 high-risk non-carriers matched for cancer type and age at diagnosis, and 192 healthy Ashkenazi women were screened, using DHPLC and restriction methods. The 471delAAAG mutation was detected in a single male with prostate cancer (1/294, 0.3%), in two ovarian cancer patients (2/141, 1.4%) and in one of 242 healthy controls (0.41%). An abnormal DHPLC profile identical to the one produced by the 471delAAAG mutation was noted in 23 additional women. The rate of this polymorphism was significantly elevated in high-risk non-carrier women (16/205; 7.8%) than in BRCA1/2 carriers (2/209; 1.0%) and controls (5/192; 2.6%) (chi = 11.670; P < 0.001). Sequence analysis disclosed a silent polymorphism in Valine at codon 118: c.353 C- > T.The 471delAAAG mutation occurs rarely in Israeli prostate and breast/ovarian cancer patients. A silent polymorphism in the RNASEL gene occurs more prevalently in high-risk Ashkenazi breast/ovarian cancer patients without a BRCA1/2 mutation.

BACKGROUND:The precise genes involved in conferring prostate cancer risk in sporadic and familial cases are not fully known. OBJECTIVES:To evaluate the genetic profile within several candidate genes of unselected prostate cancer cases and to correlate this profile with disease parameters. METHODS:Jewish Israeli prostate cancer patients (n = 224) were genotyped for polymorphisms within candidate genes: p53, ER, VDR, GSTT1, CYP1A1, GSTP1, GSTM1, EPHX and HPC2/ELAC2, followed by analysis of the genotype with relevant clinical and pathologic parameters. RESULTS:The EPHX gene His113 allele was detected in 21.4% (33/154) of patients in whom disease was diagnosed above 61 years, compared with 5.7% (4/70) in earlier onset disease (P < 0.001). Within the group of late-onset disease, the same allele was noted in 5.5% (2/36) with grade I tumors compared with 18% (34/188) with grade II and up (P = 0.004). All other tested polymorphisms were not associated with a distinct clinical or pathologic feature in a statistically significant manner. CONCLUSIONS:In Israeli prostate cancer patients, the EPHX His113 allele is seemingly associated with a more advanced, late-onset disease. These preliminary data need to be confirmed by a larger and more ethnically diverse study.