Jewish Individuals Research Articles

A636P is associated with early-onset colon cancer in Ashkenazi Jews.

Hereditary predisposition to colorectal cancer most often manifests itself as familial adenomatous polyposis from mutations of APC, or hereditary nonpolyposis colorectal cancer, resulting from mutations of MSH2, MLH1, MSH6, or other genes. Previously, we described a rare founder mutation MSH2*1906C > G in Ashkenazi Jews that was found in 8 of 1,345 individuals (0.6%) of Ashkenazi descent with colorectal cancer. This study seeks to characterize the proportion of individuals of Ashkenazi heritage with very early-onset colon cancer (diagnosed at age 40 or younger) that could be attributed to MSH2*1906C>G. We analyzed the carrier frequency of MSH2*1906C>G in paraffin samples from 31 Jewish patients age 40 or less, diagnosed with colorectal cancer at Memorial Sloan-Kettering and lymphocyte-derived DNA from 10 patients. We did not select for family history. Genotyping for MSH2*1906C>G was performed by polymerase chain reaction and restriction enzyme digestion methods. We detected the MSH2*1906G>C mutation in 3 of the 41 samples (7.14%) of patients who had colorectal cancer diagnosed at age 40 or younger. This incidence is significantly greater than the 8 in 1,345 (0.6%) we observed for cases of colorectal cancer in Ashkenazi Jews not selected for age (p = 0.004). Although very rare in the population, MSH2*1906G>C is found at an increased frequency in young Jewish patients with colorectal cancer. These results suggest that testing for the MSH2*1906G>C mutation should be included in the evaluation of Ashkenazi Jewish individuals diagnosed with early-onset colon cancer.

Multiplexed fluorescence analysis for mutations causing Tay-Sachs disease.

AbstractTay-Sachs disease is a severe, neurodegenerative disease fatal in childhood that is caused by deficiency of the enzyme β-hexosaminidase A (Hex A) (1). Tay-Sachs is most common in the Ashkenazi Jewish population, with an incidence of 1/3600 affected individuals and a carrier rate of approx 1 in 30 (1). Owing to the severity of the disease and the high incidence, carrier screening for Tay-Sachs disease has been available to Ashkenazi Jewish individuals since the 1970s, which has greatly reduced the number of affected children in this population. The standard method of carrier testing is by biochemical analysis for reduced Hex A activity in serum (2).KeywordsMutant AlleleCarrier ScreeningCarrier TestingAshkenazi Jewish PopulationResultant Polymerase Chain Reaction ProductThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

STR data for 13 loci from Jewish populations

A total of 124 Jewish individuals, categorized into four groups, have been analyzed for 13 STR loci. No significant differences between the groups were found, except for the FGA system. A high level of genetic variability was found in the overall population.

Refraiming the study of contemporary American Jewish Identity

The 30-year enterprise of studying American Jewish identification and involvement in Jewish life has been based mainly on sociodemographic surveys. These surveys have tracked the activity levels of Jewish individuals in terms of ritual practice, cultural and educational involvements and institutional affiliations, philanthropic giving, and friendship networks, but they have not looked directly at Jewish identity as understood in the psychological sense. The bulk of the research about American Jewish identity during this period has centered on the question, How Jewish are American Jews, whether in comparison to other American ethnic groups (in terms of structural distinctiveness), in comparison to Jews of prior generations, or in comparison to an idealized way of being Jewish. Yet it is more apparent than ever that the important issues about the nature of contemporary American Jewishness fall along a different frontier. A new question has emerged. How are American Jews Jewish? In what ways, if any do they connect to Jewishness and Judaism? American Jewry is more diverse and dispersed than before, and the Jewish group in America today is characterized by a degree of integration and social acceptance that contrasts sharply to the situation 50 years ago or to Europe in the 18 century. In this new environment no one is either forced to be Jewish or to escape from being Jewish. The dynamic of acceptance versus rejection or belligerence regarding one’s Jewishness has been replaced by a dynamic of finding Jewishness to be meaningful or remaining indifferent to it. Jewish continuity of the group as a whole has come to depend on the individual’s commitments and decision-making. For this reason, in addition to looking at Jewish practices and involvements in Jewish life, it is essential to examine the subjective, inner experience of being Jewish.

Du heder aux écoles actuelles : l'éducation juive, reflet d'un destin collectif

The author endeavours to show how, starting from the modern era to our days, the Jewish education has always depended on the successive identity types to which the Jewish minority in France chose to belong. Following the heder of the Jewish nations of the « ancien regime », the consistorial school comes after the emancipation with its difficult challenge : promoting Jewish individuals into the communal society and at the same time the acknowledgement by each one of his religious specificity. Primarily a favourite means of regenerating for the poor and the immigrant Jewish people, this means of improvement reaches the end of the thirties, unhappily weakening because of the success of the assimilation and the social secularisation of general society. Between the two World Wars and mainly on the eve of the second one, the first weaknesses begin to appear in French Judaism as a whole, and yearnings for a more religious aspect of the identity and a more favourable interest for zionism, although many still remain convinced « Israelites ». These yearnings are manifest in the newly born youth movements, mostly the French Israelite boy-scouts, and the creation of the Maimonide college in Paris, and, during the period of the occupation, will meet favourable conditions for their growth and the birth of new structures. However this renewal is transient. Not until the sixties and more effectively the seventies, the outburst of Jewish educational opportunities will be offered, and then the collapsing of the French Israelite model is the fundamental reason for this outburst.

Allele frequencies of nine STR loci of Jewish and Arab populations in Israel.

DNA typing of nine short tandem repeat (STR) loci was carried out on unrelated Israeli Jewish and Arab individuals. All loci were highly polymorphic and the distribution of the obtained genotypes did not deviate from Hardy-Weinberg equilibrium. A comparison between Jewish and Arab population data revealed statistically significant differences in allele frequency distributions for some of the loci. The results presented in this study enable the use of these nine STR loci for forensic, identification and paternity cases in the Jewish and the Arab populations of Israel.

Apples from the Desert (review)

Reviewed by: Apples From the Desert Stacy N. Beckwith Apples From the Desert, by Savyon Liebrecht. New York: The Feminist Press at the City University of New York, 1998. 234 pp. $19.95. Apples from the Desert is the first collection in English of short stories by one of Israel’s most lyrical, penetrating, and measured women authors, Savyon Liebrecht. The volume is the fourth to appear in the Helen Rose Scheuer Jewish Women’s Series, of the Feminist Press at the City University of New York. Comprising stories published in Hebrew between 1986 and 1992, this collection introduces Savyon Liebrecht to English readers as a writer who, finely translated, interweaves past and present times, and the coping efforts of Jewish and Arab individuals, families, and communities, in ways that invite repeated exploration of the intimate texture of contemporary life in Israel. Savyon Liebrecht was born in Germany in 1948 to Holocaust survivors from Poland. She came to the newly established State of Israel as a young girl. The particular strength of this anthology is that it allows the first- or second-hand Holocaust memories of a number of Liebrecht’s central characters to mingle with the personal resonances of the more current Israeli-Palestinian conflict, as the reader moves through the stories and experiences the echo of those just finished. Lily Rattok is a prominent scholar of Hebrew literature and a pioneer of Women’s Studies in Israel. As she explains in her introduction to this volume, Savyon Liebrecht was raised in a household that remained tethered to her parents’ memories of the Holocaust and to their past struggles for survival. The particular language of this formative home was silence, while visual exchange, through glances and meaningful looks, as well as facial expressions, enabled more substantive communication. In 1982, European film critic Yvette Biró described “visual thinking” as the cinematographer’s awareness that the human eye, both on and in society, “always compares.” 1 “Seeing is the confrontation of perception and knowledge,” per Biró, and in their varying realization of this, as if captured on film, Liebrecht’s characters exhibit their private and socially driven fears and foibles in sharp relief. Rattok writes that, “Liebrecht tries to play the role of a healer, presenting possibilities for mending the rifts that threaten the existence of Israeli society” (p. 20). The author may appear to be such a mender with respect to the cross-cultural encounters she sets up. These include confrontations between young Israelis and their seemingly intractable Holocaust survivor relatives, and encounters between different generations of Israelis with distinct socio-historical perspectives. Liebrecht also portrays relations between more and less advantaged Ashkenazic and Sephardic Israeli Jews, between Jews and Arabs, and in each of the above categories, encounters among and between men and women. [End Page 141] However, once brought together, Liebrecht’s various selves and Others develop through the eye of a realist. Liebrecht does not allow past trauma, of whatever magnitude, to beatify survivors in a modern, fast-paced Israel, nor new cross-cultural experiences, often registered in meaningful looks, to herald cure-all ententes. Even in the space of a short story, Liebrecht’s elderly characters are fascinating because of their obsessions and their inescapable degrees of self-centeredness. In this way they are on par with the protagonists in the only full-length Israeli novel to focus on an interplay of indomitable personalities in a suburban old age home and in Tel Aviv: Yehoshua Kenaz’s The Way to the Cats (1991). 2 From a different angle, the surprising insight that a young Ashkenazi war widow gains from her Sephardic mother-in-law after a silence of twelve years, illustrates the distance traveled by Israeli literature in representing this type of encounter. Savyon Liebrecht’s story, “Written in Stone,” reads like an inversion of Israel’s first urban, “inter- ethnic,” and immensely popular novel, The Street of Steps. 3 Set in Haifa in the early 1950s, the daughter of a wealthy Ashkenazi entrepreneur (Erella, just as in Liebrecht’s story) has thoughts of marrying a motherless young man from the city’s squalid Sephardic district. Beyond the anger of her father, Erella is ultimately dissuaded...

Jewish population genetic data in 20 polymorphic loci

Frequency data of 20 polymorphisms (13 autosomal and 6 Y-chromosome STRs and the Alu-insertion YAP) were determined in a sample of 124 unrelated Jewish individuals from Ashkenazi, Sephardic, North African and Oriental origin. The a priori statistical power of the set of studied loci was highly discriminating (PD=1 in 2.393 E+15 individuals for autosomal STRs, and a probability of finding two unrelated males with the same haplotype of less than 0.01). Some significant population differences were registered between Jews and other Circummediterranean populations in Y-chromosome loci frequencies.

Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) in ethnic populations in Texas; a report of a novel MTHFR polymorphic site, G1793A.

The importance of hyperhomocysteinemia, birth defects, and vascular diseases has been the subject of intense investigations. The polymorphic MTHFR mutations (C677T and A1298C) cause mild hyperhomocysteinemia, especially in homozygotes for C677T, but also in compound heterozygotes for C677T/A1298C. The subject of this report is the frequency of the polymorphic mutations in the MTHFR gene C677T, C1298A, and newly discovered mutation G1793A, as well as the association with MTRR polymorphic site A66G in different ethnic groups. Four ethnic groups were studied: African-Americans, Caucasians, Hispanics, and Ashkenazi Jews. There are statistically significant differences in the frequency of these alleles in the different populations studied, which impacts compound heterozygosity for such alleles in these populations. DNA samples obtained from the blood of healthy individuals of African-Americans, Hispanics, and Caucasians from south Texas were analyzed and compared to those obtained from Ashkenazi Jewish individuals. The polymorphic site, the G1793A allele, is least frequent among Ashkenazi individuals, 1.3%, compared to 6.9% among Caucasians (P = 0.001), 5.8% among Hispanics (P = 0.012), and 3.1% among African-Americans. The MTRR polymorphic site shows the lowest allele frequency among Hispanics, 28.6%, compared to 34% among African-Americans, 43.1% among Ashkenazi Jews (P = 0.002), and 54.4% among Caucasians (P < 0.0001). Statistically significant differences in allele frequencies of C677T and C1298A polymorphisms were also observed in these populations. Compound heterozygosity for multiple polymorphic alleles may play a role in birth defects and vascular diseases.

Genetic analysis of the APC gene regions involved in attenuated APC phenotype in Israeli patients with early onset and familial colorectal cancer.

The genetic basis for the majority of early onset or non-syndromic ‘familial’ colorectal cancer (CRC) is unknown. Attenuated APC phenotype is characterized by relatively few colonic polyps, early age at onset of colon cancer compared with the general population, and inactivating germline mutations within specific regions of the APC gene. We hypothesized that germline mutations within these APC gene regions, might contribute to early onset or familial CRC susceptibility. To test this notion, we analysed 85 Israeli patients with either early onset (< 50 years at diagnosis) or familial CRC for harbouring mutations within the relevant APC gene regions: exons 1–5, exon 9 and a region within exon 15 (spanning nucleotides c.3900 to c.4034; codons 1294 to 1338) using denaturing gradient gel electrophoresis (DGGE), and all of exon 15 employing protein truncation test (PTT). No inactivating, disease-associated mutations were detected in any patient. A novel polymorphism in intron 5 was detected in 16 individuals, 8 patients were carriers of the 11307K variant, a mutation prevalent among Jewish individuals with colorectal cancer, and 4 displayed the E1317Q variant. We conclude that in Israeli individuals with early onset or familial CRC, truncating mutations in the APC gene regions associated with attenuated APC phenotype probably contribute little to disease pathogenesis. © 2001 Cancer Research Campaign http://www.bjcancer.com

The I1307KAPCPolymorphism: Prevalence in Non-Ashkenazi Jews and Evidence for a Founder Effect

A missense mutation within the APC gene, I1307K, was described in Ashkenazi individuals at risk for colorectal cancer (CRC) and in the general population. The anecdotal reporting of the occurrence of this mutation in some non-Ashkenazi individuals led us to hypothesize that within the Jewish people, the I1307K polymorphism may reflect a founder mutation, and that the mutation is not restricted to ethnic Ashkenazis. To test that notion, and to establish the occurrence rate of the I1307K polymorphism in non-Ashkenazi Jewish populations, we screened Iraqi and Moroccan Jews and consecutive Jewish CRC patients and performed haplotype analysis with APC-linked markers in two I1307K carrier families. We analyzed Jewish individuals: 210 Moroccans, 160 Iraqis, 148 Ashkenazi, and 349 CRC patients (227 Ashkenazi and 122 non-Ashkenazi). The mutation detection scheme included PCR followed by denaturing gradient gel electrophoresis (DGGE) or modified restriction analysis (MRA). Haplotypes were assessed using three intragenic and three flanking markers. The I1307K polymorphism was detected in 29/227 Ashkenazi (12.8%), 2/122 (1.6%) non-Ashkenazi CRC patients, and in 2 individuals each (approximately 1%) within the Moroccan and Iraqi populations. Allelic pattern analysis in all our I1307K carriers, revealed a common haplotype for the three intragenic markers tested, in all mutation carriers, regardless of ethnic origin. The I1307K polymorphism, therefore, exists in all ethnic Jewish populations: Ashkenazi and non-Ashkenazi, with or without colon cancer. Jewish I1307K mutation carriers share a common allelic pattern with APC-linked markers. This strongly supports the notion of a founder mutation for I1307K.

Nonradioactive Detection of the Common Connexin 26 167delT and 35delG Mutations and Frequencies among Ashkenazi Jews

Mutations in the gap junction β2 (GJB2) gene, Connexin 26 (Cx26), cause nonsyndromic sensorineural recessive deafness (NSRD). Two frameshift mutations, 167delT and 35delG, are the most frequent Cx26 lesions causing NSRD. The 35delG mutation is panethnic, while the 167delT lesion occurs almost exclusively in the Ashkenazi Jewish population at a carrier frequency of 2 to 4%. To facilitate carrier detection, a simple nonradioactive allele-specific oligonucleotide (ASO) hybridization assay was developed for the 167delT and 35delG mutations. Screening of 1012 anonymous Ashkenazi Jewish individuals from the New York Metropolitan area revealed carrier frequencies for 167delT and 35delG of 3.96% (95% CI: 2.75–5.15%) and 0.69% (95% CI: 0.18–1.20%), respectively. This sensitive, specific, and relatively inexpensive method can reliably identify affected newborns and patients with NSRD as well as facilitate carrier screening for Connexin 26 deafness in the Ashkenazi Jewish community.

Rapid detection of the two common mutations in Ashkenazi Jewish patients with mucolipidosis type IV.

Among Ashkenazi Jewish individuals with mucolipidosis IV (ML IV), two mutations in the ML IV gene, IVS3-1A --> G and delEX1-EX7, account for more than 95% of disease alleles. The reported method of genotyping for the delEX1-EX7 mutation involves a cumbersome multistep procedure. In the present study, a new simplified one-step procedure is described that detects this mutation in both patients and carriers. An improved procedure is also described for detection of the IVS3-1A --> G mutation. Using these improved procedures, we have characterized the ML IV mutant alleles in 27 patients and 95 of their relatives from 22 families, and in 123 unrelated and unaffected Ashkenazi Jewish controls. Of the 27 ML IV patients, 16 patients (59.3%) were found to be homozygous for the IVS3-1A --> G mutation and 1 patient (3.7%) homozygous for the delEX1-EX7 mutation. Additionally, 9 patients (33.3%) were compound heterozygotes for IVS3-1A --> G/delEX1-EX7. Among the 123 Ashkenazi Jewish controls, two individuals were identified as heteroallelic with one IVS3-1A --> G mutation (carrier frequency: approximately 1 in 61); none showed the delEX1-EX7 mutation. The modifications described here provide a more facile means of genotyping patients and carriers and expand the possibilities for screening at-risk populations.

Prevalence of cystic fibrosis mutations in Israeli Jews.

The aim of this study was to evaluate the screening policies of cystic fibrosis (CF) in the Jewish population. The prevalence of mutations that account for CF in Israel have been defined in the past by determining the frequency of CF mutations in affected individuals. This study is a population-based study and is, therefore, different from previous patient-based studies. We found that the CF mutations D1152H, W1089X, and 405 + IG-->A were present in some ethnic groups in which no CF patients carrying these mutations were reported. These facts necessitate a reevaluation of the screening policy regarding the ethnic groups in Israel. We studied 9,430 healthy Jewish Israeli individuals of 36 countries of origin. The prevalence of CF mutations was 1:19, 1:19, 1:28, and 1:42 for the Ashkenazi, Sephardi, North African, and Eastern Jews, respectively. CF mutations were identified in 374 (4.0%) individuals. These included 173 (46.3%) carriers of the W1282X mutation; 110 (29.4%) found to carry delF508; 23 (6.1%) who carried G542X; 22 (5.9%) who carried 3849 + 10Kb (C-->T; 20 (5.3%) who carried D1152H; 10 (2.7%) who carried N1303K; 11 (2.9%) who carried 405 + IG-->A; 4 (1.1%) who carried W1089X; and one (0.3%) who carried S549R. No carriers were detected for the 1717-1G-->A, G85E, and T360K mutations, which were tested for in 7,383, 1,558, and 41 individuals, respectively.

Familial Dysautonomia Is Caused by Mutations of the IKAP Gene

The defective gene DYS, which is responsible for familial dysautonomia (FD) and has been mapped to a 0.5-cM region on chromosome 9q31, has eluded identification. We identified and characterized the RNAs encoded by this region of chromosome 9 in cell lines derived from individuals homozygous for the major FD haplotype, and we observed that the RNA encoding the IkappaB kinase complex-associated protein (IKAP) lacks exon 20 and, as a result of a frameshift, encodes a truncated protein. Sequence analysis reveals a T-->C transition in the donor splice site of intron 20. In individuals bearing a minor FD haplotype, a missense mutation in exon 19 disrupts a consensus serine/threonine kinase phosphorylation site. This mutation results in defective phosphorylation of IKAP. These mutations were observed to be present in a random sample of Ashkenazi Jewish individuals, at approximately the predicted carrier frequency of FD. These findings demonstrate that mutations in the gene encoding IKAP are responsible for FD.

Consent to the use of stored DNA for genetics research: A survey of attitudes in the Jewish population

The use of anonymized stored tissue is a routine practice in genetic research. Investigators who utilize stored samples are neither required nor able to obtain informed consent before each use. Many genetic studies, however, are conducted on specific ethnic populations (e.g., Ashkenazi Jews). The results in these cases, although individually anonymous, are not anonymous with respect to the ethnicity of the participants. This lack of group anonymity has led to concern about the possibility of stigmatization and discrimination based on the results of the genetic research. In the present study we surveyed Jewish individuals about their attitudes regarding the practice of using stored DNA samples for genetic research. Specifically, we were interested in whether attitudes about informed consent and willingness to participate in genetics research using stored DNA would depend on the circumstances in which the material was collected (i.e., clinical setting vs. research setting) and the characteristics of the disease or trait under investigation. Overall, most respondents reported that written informed consent should be required and that they would be willing to provide such consent. Participants were most willing to provide consent, however, when the sample had been collected in a research rather than clinical setting. Further, participants were more likely to endorse the need for obtaining consent when the sample was collected in a clinical setting. Finally, participants were significantly less willing to participate in research that examined stereotypical or potentially stigmatizing traits as opposed to research that examined medical or mental illnesses. © 2001 Wiley-Liss, Inc.

The Tyr978X BRCA1 Mutation in Non-Ashkenazi Jews: Occurrence in High-Risk Families, General Population and Unselected Ovarian Cancer Patients

Background: In Jewish individuals of Ashkenazi (East European) decent, three predominant mutations, 185 delAG and 5382insC (BRCA1) and 6174delT (BRCA2), seem to account for a substantial portion of germline mutations in high-risk breast/ovarian cancer families. Among non-Ashkenazi Jews, the 185delAG and the Tyr978X mutations, as well as several ‘private’ mutations have been reported within the BRCA1 gene. Objective: Assessing the occurrence rate of the Tyr978X BRCA1 germline mutation in Jewish non-Ashkenazi individuals: high-risk familial cases, unselected ovarian cancer patients and the general average risk Jewish Iraqi population. In addition, finding proof that this is a founder mutation. Methods: PCR amplification of the relevant fragment of the BRCA1 gene from constitutional DNA followed by restriction enzyme digest that differentiates the wild type from the mutant allele. In addition, BRCA1-linked markers were used for haplotype analysis. Results: The Tyr978X BRCA1 mutation was detected in 3/289 (1%) of the average-risk Jewish Iraqi population, in 7/408 (1.7%) high-risk Jewish non-Ashkenazi individuals (representing 332 unrelated families) and in 1/81 (1.2%) of unselected Jewish non-Ashkenazi ovarian cancer patients. Allelotyping using BRCA1-linked markers revealed an identical allelic pattern in all mutation carriers with the intragenic markers. Conclusions: Our findings suggest that this mutation is prevalent in Iraqi Jews, represents a founder mutation, and should be incorporated into the panel of mutations analyzed in high-risk families of the appropriate ethnic background.

Consent to the use of stored DNA for genetics research: a survey of attitudes in the Jewish population.

The use of anonymized stored tissue is a routine practice in genetic research. Investigators who utilize stored samples are neither required nor able to obtain informed consent before each use. Many genetic studies, however, are conducted on specific ethnic populations (e.g., Ashkenazi Jews). The results in these cases, although individually anonymous, are not anonymous with respect to the ethnicity of the participants. This lack of group anonymity has led to concern about the possibility of stigmatization and discrimination based on the results of the genetic research. In the present study we surveyed Jewish individuals about their attitudes regarding the practice of using stored DNA samples for genetic research. Specifically, we were interested in whether attitudes about informed consent and willingness to participate in genetics research using stored DNA would depend on the circumstances in which the material was collected (i.e., clinical setting vs. research setting) and the characteristics of the disease or trait under investigation. Overall, most respondents reported that written informed consent should be required and that they would be willing to provide such consent. Participants were most willing to provide consent, however, when the sample had been collected in a research rather than clinical setting. Further, participants were more likely to endorse the need for obtaining consent when the sample was collected in a clinical setting. Finally, participants were significantly less willing to participate in research that examined stereotypical or potentially stigmatizing traits as opposed to research that examined medical or mental illnesses.

Resistive Play

In this article, the author argues that the current Jewish sports movement exemplifies and symbolizes a “new Jewish visibility” in Vienna’s sociocultural field. It is thus part and parcel of a larger recent transformation that has brought Jewish individuals, collectivities, and institutions into Austria’s public sphere. Drawing on his ethnographic research on postwar Austrian-Jewish culture, the author argues that sport represents a privileged site in this development through its construction of an affirmative public Jewish subjectivity, negotiated, in turn, in light of the social reality of a recently expanding Jewish community.

The rate of the founder Jewish mutations in BRCA1 and BRCA2 in prostate cancer patients in Israel.

Inherited predisposition occurs in 5–10% of all prostate cancer (CaP) patients, but the genes involved in conferring genetic susceptibility remain largely unknown. Several lines of evidence indicate that germline mutations in BRCA1 and BRCA2 might be associated with an increased risk for CaP. Three mutations in these two genes (185delAG and 5382InsC (BRCA1) and 6174delT (BRCA2) occur in about 2.5% of the general Ashkenazi population, and the 185delAG BRCA1 mutation, in up to 1% of non-Ashkenazi Jews. In order to assess the contribution of these germline mutations to prostate cancer in Jewish Israeli patients, we tested 174 unselected prostate cancer patients (95 of Ashkenazi origin) for these mutations by PCR amplification and modified restriction enzyme digests. Patient’s age range was 45–81 years (median 66), and in 24 (14.4%) the disease was diagnosed prior to 55 years of age. Nineteen (11%) and 12 (6.9%) patients had a first or second degree relative with CaP or breast cancer, respectively. Overall, five mutation carriers were detected: 2/152 (1.3%) 185delAG, 2/104 (2%) 5382InsC, and 1/158 (0.6%) 6174delT. In all carriers, the disease was diagnosed after the age of 55, and only one of them had a family history of breast and CaP. In addition, no allelic losses at the BRCA1 locus were demonstrated in 17 patients with a family history of CaP, using seven microsatellite markers. We conclude that the rate of the predominant Jewish BRCA1 and BRCA2 mutations in CaP patients does not significantly differ from that of the general population, and that mutational inactivation of the BRCA1 is rare in familial CaP. Thus, germline BRCA1 and BRCA2 mutations probably contribute little to CaP occurrence, to inherited predisposition, and to early onset disease in Jewish individuals. © 2000 Cancer Research Campaign