The 471delAAAG mutation and C353T polymorphism in the RNASEL gene in sporadic and inherited cancer in Israel.

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.