TY - JOUR
T1 - Coinheritance of BRCA1 and BRCA2 mutations with Fanconi anemia and Bloom syndrome mutations in Ashkenazi Jewish population
T2 - Possible role in risk modification for cancer development
AU - Koren-Michowitz, M.
AU - Friedman, E.
AU - Gershoni-Baruch, R.
AU - Brok-Simoni, F.
AU - Patael, Y.
AU - Rechavi, G.
AU - Amariglio, N.
PY - 2005/3
Y1 - 2005/3
N2 - Fanconi anemia (FA) and Bloom syndrome (BS) are rare autosomal recessive genetic disorders manifesting in childhood, with a predisposition to cancer development in adolescence and adulthood. Both syndromes are relatively prevalent among the Ashkenazi Jewish population, and, in both syndromes, mutations specific to this population have been identified. Similarly, unique Ashkenazi mutations were found in the genes BRCA1 and BRCA2. These two genes, when mutated, play important roles in familial breast and ovarian carcinogenesis. The genes involved in the pathogenesis of the FA and BS belong to the general class of instability genes. Heterozygosity for the FA gene has no known promalignant potential, while the BS mutation carrier state was associated with an increased frequency of colorectal cancer. The especially frequent carrier state among the Ashkenazi Jewish population coupled with the high prevalence of BRCA1 and BRCA2 in the same population has led us to search for coinheritance affecting the potential for cancer development. One hundred Ashkenazi women with known BRCA1 and BRCA2 mutations were screened for the FA mutation IVS4+4 A→T and the BS mutation blmAsh. Our results indicate that there is an increased prevalence of both FA and BS mutation carriers among the population studied compared with the general Ashkenazi population (prevalence of FA mutation 4/100 women [4%] as compared to 35/3104 previously published controls [1.1%], P = 0.031, and for BS mutation 3/100 [3.2%] as compared to 36/4001 [0.9%], P = 0.058). There was no statistically significant effect of the coinheritance on cancer prevalence, type of cancer, or age of cancer onset. Coinheritance of FA and/or BS mutations seems to be more prevalent among BRCA mutation carriers, but a larger study encompassing more women may help in clarifying this issue.
AB - Fanconi anemia (FA) and Bloom syndrome (BS) are rare autosomal recessive genetic disorders manifesting in childhood, with a predisposition to cancer development in adolescence and adulthood. Both syndromes are relatively prevalent among the Ashkenazi Jewish population, and, in both syndromes, mutations specific to this population have been identified. Similarly, unique Ashkenazi mutations were found in the genes BRCA1 and BRCA2. These two genes, when mutated, play important roles in familial breast and ovarian carcinogenesis. The genes involved in the pathogenesis of the FA and BS belong to the general class of instability genes. Heterozygosity for the FA gene has no known promalignant potential, while the BS mutation carrier state was associated with an increased frequency of colorectal cancer. The especially frequent carrier state among the Ashkenazi Jewish population coupled with the high prevalence of BRCA1 and BRCA2 in the same population has led us to search for coinheritance affecting the potential for cancer development. One hundred Ashkenazi women with known BRCA1 and BRCA2 mutations were screened for the FA mutation IVS4+4 A→T and the BS mutation blmAsh. Our results indicate that there is an increased prevalence of both FA and BS mutation carriers among the population studied compared with the general Ashkenazi population (prevalence of FA mutation 4/100 women [4%] as compared to 35/3104 previously published controls [1.1%], P = 0.031, and for BS mutation 3/100 [3.2%] as compared to 36/4001 [0.9%], P = 0.058). There was no statistically significant effect of the coinheritance on cancer prevalence, type of cancer, or age of cancer onset. Coinheritance of FA and/or BS mutations seems to be more prevalent among BRCA mutation carriers, but a larger study encompassing more women may help in clarifying this issue.
KW - BRCA1
KW - BRCA2
KW - Bloom syndrome
KW - Fanconi anemia
UR - http://www.scopus.com/inward/record.url?scp=14644389348&partnerID=8YFLogxK
U2 - 10.1002/ajh.20310
DO - 10.1002/ajh.20310
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 15726604
AN - SCOPUS:14644389348
SN - 0361-8609
VL - 78
SP - 203
EP - 206
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 3
ER -