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עמוד בית
Mon, 15.07.24

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October 2008
L. Keinan-Boker, L. Lerner-Geva, B. Kaufman and D. Meirow

The frequency of pregnancy-associated breast cancer, a rare but serious occurrence, may increase in light of the secular trends for lower parity in general and for an older age at first full-term delivery in particular. Data on PABC[1] in individuals who are at high risk for breast cancer are limited. A computerized search of PUBMED showed that the reported incidence of PABC is 1:3000 pregnancies; it is often diagnosed at an advanced stage and its prognosis is inferior compared to non-PABC. Carriers of mutations in the genes BRCA1/2 may present a specific high risk group for PABC especially at younger ages. Women treated with fertility treatment drugs may be at a higher risk for PABC as well.  






[1] PABC = pregnancy-associated breast cancer


November 2007
Y. Laitman, B. Kaufmann, E. Levy Lahad, M.Z. Papa and E. Friedman

Background: Germline mutations in BRCA1 and BRCA2 genes account for only 20–40% of familial breast cancer cases. The CHEK2 gene encodes a checkpoint kinase, involved in response to DNA damage, and hence is a candidate gene for breast cancer susceptibility. Indeed, the CHEK2*1100delC truncating mutation was reported in a subset of mostly North European breast cancer families. The rate of the CHEK2*1100delC variant in the Ashkenazi* Jewish population was reported to be 0.3%.

Objectives: To evaluate whether CHEK2 germline mutations contribute to a breast cancer predisposition in Ashkenazi-Jewish high risk families.

Methods: High risk Ashkenazi Jewish women, none of whom was a carrier of the predominant Jewish mutations in BRCA1/BRCA2, were genotyped for germline mutations in the CHEK2 gene by exon-specific polymerase chain reaction followed by denaturing gradient gel electrophoresis and sequencing of abnormally migrating fragments.

Results: Overall, 172 high risk women were genotyped: 75 (43.6%) with breast cancer (average age at diagnosis 49.6 ± 9.6 years, mean ± SD) and 97 asymptomatic individuals (age at counseling 48.3 ± 8.2 years). No truncating mutations were noted and four previously described missense mutations were detected (R3W 1.2%, I157T 1.2%, R180C 0.6% and S428F 5%), one silent polymorphism (E84E 20.5%) and one novel missense mutation (Y424H 1.2%). Segregation analysis of the I157T and S428F mutations (shown to affect protein function) with the cancer phenotype showed concordance for the CHK2*I157T mutation, as did two of three families with the CHK2*S428F mutation.

Conclusions: CHEK2 missense mutations may contribute to breast cancer susceptibility in Ashkenazi Jews.

 






*  Of East European descent


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