Israel Medical Association Journal

Background: Recent genetic susceptibility findings in Jews of Eastern European descent, commonly called Ashke­nazi Jews, have led to concerns that they may be stigmatized as being more cancer prone than other groups.

Objective: To examine the hypothesis that site-specific or all-cancer incidence and mortality rates are higher than expected in Ashkenazi Jews worldwide when compared with referent populations.

Methods: A MEDLINE search was performed using keywords "Jews", "cancer", "incidence" and "mortality" to identify studies directly relevant to the primary study question.

Results: Little evidence suggested that all-cancer inci­dence or mortality is higher in Ashkenazi Jews than in North American non-Hispanic whites. Ashkenazi Jewish men appear to have relatively low cancer rates, which may be due to lower tobacco use. Colorectal cancer was shown to disproportio­nately overburden Ashkenazi Jews, who may also be at increased risk for ovarian, pancreatic and stomach cancer, and non-Hodgkin’s lymphoma. Little evidence was found support­ing an elevated risk of breast cancer in Ashkenazi Jewish women. Rates of lung, cervical, penile and prostate cancers appear low in this population. Rate disparities were generally attributed to lifestyle differences, particularly diet and tobacco use, rather than to genetic predisposition.

Conclusions: Ashkenazi Jews do not appear to have a higher total cancer burden than comparable North American populations. Any cancer rate differentials in this group are more likely to be related to lifestyle and dietary factors than to genetics. However, colorectal cancer rates in Ashkenazi Jews may be the highest of any ethnic group in the world and cancer controllers should consider this when developing future screening, diagnostic and policy strategies.

The screening program in Israel for Tay-Sachs disease has proven very successful, giving Jewish couples a choice not to have affected children. The technology of carrier detection is now possible in several other severe genetic diseases that are relatively frequent among Jews. Due to the current confusion, a policy is needed to determine how the TSD screening program should be continued in the Israeli Jewish population. We propose that such a screening program include only mutations agreed by consensus as causing a disease severe enough to warrant the possibility of therapeutic abortion. We also propose that general screening include only mutations that are relatively frequent, taking into account the carrier frequencies in the Israeli Jewish population.

Background: Achondroplasia is the most frequent form of disproportionate short stature, characterized by rhizomelic shortening of the limbs. This disorder is inherited as an autosomal dominant trait, although most of the cases are sporadic, a result of a de novo mutation. A recurrent glycine to arginine mutation at codon 380 (G380R) in the transmembrane domain of the fibroblast growth factor receptor 3 gene was found to cause achondroplasia among different populations. This is most uncommon in other autosomal dominant genetic diseases.

Objectives: To determine whether this mutation is also common among Jewish patients from diverse ethnic groups and among the Arab population in Israel.

Methods: We examined the G380R mutation (G>A and G>C transition) and the mutation G375C (G>T transition at codon 375) in 31 sporadic patients and in one family diagnosed clinically to have achondroplasia.

Results: We found the G>A transition at codon 380 in 30 of our patients and the G>C transition in one patient. We were not able to detect any of the three mutations in two patients with an atypical form of achondroplasia.

Conclusions: Our results further support the unusual observation that nucleotide 1138 of the FGFR3 gene is the most mutable nucleotide discovered to date across different populations.

_________________________________

FGFR3 = fibroblast growth factor receptor 3