RESUMO
The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with reduced enzyme activity, hyperhomocysteinaemia and increased risk for atherosclerosis in homozygotes. We examined the frequency of this mutation and its association with disease pattern in 491 Jewish women with either sporadic (n = 355; 72%) or hereditary (n = 136; 28%) breast and/or ovarian cancer and in 69 asymptomatic BRCA1/2 mutation carriers, genotyped for the three predominant Jewish founder BRCA1/2 mutations (185delAG, 5382insC and 6174delT). 677T homozygotes were equally distributed among women with sporadic breast and/or ovarian cancer (71/355; 20.0%) and among BRCA1/2 mutation carriers (43/205; 21.0%) (P=non-significant). 677T homozygotes were equally distributed among women diagnosed with breast cancer prior to (22/122; 18.0%) and after 42 years of age (42/243; 17.3%). Among BRCA1/2 carriers, the rate of 677T homozygotes in manifesting cancer (32/136; 23.5%) and asymptomatic individuals (11/69; 15.9%) was not significantly different. The rate of 677T homozygotes (24/72; 33.3%) was higher (P=0.0026) among women with bilateral breast cancer and those with both breast and ovarian carcinoma than among those with unilateral breast cancer (64/365; 17.5%). Differences in morbidity (one versus multiple breast/ovarian tumours) are mainly attributed to 677T homozygosity and partly to BRCA1/2 mutations. Confirmation of these data, namely, that the 677T allele is significantly more common in cases of bilateral breast cancer or combined breast and ovarian cancer would have important clinical implications.
Assuntos
Proteína BRCA1/genética , Neoplasias da Mama/genética , Judeus/genética , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Polimorfismo Genético/genética , Fatores de Transcrição/genética , Adulto , Proteína BRCA2 , Neoplasias da Mama/etnologia , Estudos de Coortes , Feminino , Homozigoto , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2) , Pessoa de Meia-Idade , Neoplasias Ovarianas/etnologia , Fatores de RiscoRESUMO
We present the first report of prenatal diagnosis of X-linked hyper-IgM syndrome by PCR-mediated site directed mutagenesis (PSM) in a woman known to carry the Q220X mutation in the CD40L gene. Using the simple PSM assay, the Q220X mutation was identified by chorionic villous sampling (CVS) at 11 weeks' gestation and the pregnancy was terminated.
Assuntos
Ligante de CD40/genética , Hipergamaglobulinemia/diagnóstico , Imunoglobulina M , Mutagênese Sítio-Dirigida , Diagnóstico Pré-Natal , Adulto , Primers do DNA , Feminino , Humanos , Hipergamaglobulinemia/genética , Masculino , Reação em Cadeia da Polimerase , GravidezRESUMO
The frequency of the APC I1307K mutation and its association with disease pattern was examined in 996 Ashkenazi women consisting of individuals with either sporadic (n = 382) or hereditary (n = 143) breast and/or ovarian cancer; asymptomatic BRCA1/2 mutation carriers (185delAG, 5382insC and 6174delT) (n= 53) and healthy controls (n= 418). The I1307K allele was equally distributed among women with sporadic (17/382; 4.6%) and inherited (10/143; 7%) breast and/or ovarian cancer irrespective of their being diagnosed before or after 42 years of age and among asymptomatic (7/53; 13.2%) and cancer manifesting BRCA1/2 carriers (10/143; 7%). Taken together, the prevalence of the I1307K allele was significantly higher in BRCA1/2 carriers compared to non-BRCA1/2 carriers (17/196; 8.7% and 40/800, 5%; respectively). The high prevalence of the I1307K allele among BRCA1/2 carriers is not associated with increased cancer risk but seems to be genetically connected because of Jewish ancestry.