RESUMO
OBJECTIVES: Patients with hereditary cancer syndromes are at high risk for a second primary cancer. Early identification of these patients after an initial cancer diagnosis is the key to implementing cancer risk-reducing strategies. METHODS: A commercial laboratory database was searched for women with a history of both breast and ovarian or colorectal and endometrial cancer who underwent genetic testing for hereditary breast and ovarian cancer (HBOC) or Lynch syndrome (LS). RESULTS: Among women with both breast and ovarian cancer, 22.4% (2,237/9,982) had a BRCA1 or BRCA2 mutation. Among women with both colorectal and ovarian cancer, 28.1% (264/941) had a mutation associated with LS. In 66.6% of BRCA1 or BRCA2 mutation carriers and in 58.3% of LS mutation carriers, >5 years passed between the cancer diagnoses. Of patients with HBOC and LS, 56 and 65.2%, respectively, met the National Comprehensive Cancer Network guidelines for hereditary cancer testing after their initial diagnosis based on their personal cancer history alone. CONCLUSIONS: A substantial number of women tested for LS or HBOC after being diagnosed with two successive primary cancers were diagnosed with a hereditary cancer syndrome. In many cases, the time interval between the diagnoses was long enough to allow for the implementation of surveillance and/or prophylactic measures.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Predisposição Genética para Doença , Mutação/genética , Síndromes Neoplásicas Hereditárias/genética , Neoplasias Ovarianas/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Criança , Pré-Escolar , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Feminino , Seguimentos , Testes Genéticos , Heterozigoto , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/genética , Síndromes Neoplásicas Hereditárias/diagnóstico , Proteínas Nucleares/genética , Neoplasias Ovarianas/diagnóstico , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
Hemoglobinopathies represent a unique set of genetic disorders. Formerly, many affected individuals did not survive to childbearing age. Affected women now commonly reach childbearing age and desire pregnancy. Successful pregnancy is possible in many cases with carefully coordinated obstetric and medical management. Genetic screening and prenatal diagnosis is an important aspect of prenatal care in these disorders. DNA mutation analysis offers rapid and accurate fetal diagnosis. Pregnancy also offers a unique situation in that cord blood has become a valuable source of stem cells for transplant. This allows the potential role of the unaffected fetus as a donor for affected siblings. In addition, it was proposed that the fetus may be able to act as a donor of stem cells for an affected mother. Despite current screening recommendations,many couples are not aware that they are carriers; it is common for a child to be born with an unexpected, serious hemoglobinopathies. For this reason, newborn screening programs have been introduced in most high-risk areas. Early diagnosis can facilitate implementation of proper preventive health measures, education of the parents regarding their carrier status, and provide the child with ongoing comprehensive care.
Assuntos
Hemoglobinopatias/diagnóstico , Hemoglobinopatias/terapia , Complicações Hematológicas na Gravidez/diagnóstico , Complicações Hematológicas na Gravidez/terapia , Anemia Falciforme/diagnóstico , Anemia Falciforme/genética , Anemia Falciforme/terapia , Feminino , Aconselhamento Genético , Hemoglobinopatias/genética , Humanos , Gravidez , Cuidado Pré-Natal , Talassemia alfa/diagnóstico , Talassemia alfa/genética , Talassemia alfa/terapia , Talassemia beta/diagnóstico , Talassemia beta/genética , Talassemia beta/terapiaRESUMO
Pavlovian autoshaping conditioned responses (CRs) are complex sequences of conditioned stimulus (CS)-directed skeletal-motor responses that are elicited by CS objects predictive of food unconditioned stimulus (US). Autoshaping CRs are observed under conditions known to be conducive to elevations in plasma corticosterone levels, as, for example, in response to the eating of food as well as in response to signals predictive of food. Two experiments investigated the relationships between Pavlovian autoshaping procedures, the performance of Pavlovian autoshaping CRs, and plasma corticosterone levels in male Long-Evans rats. In Experiment 1, rats in the CS-US paired group (n=30) were given 20 daily sessions of Pavlovian autoshaping training wherein the insertion of a retractable lever CS was followed by the response-independent presentation of the food US. Tail blood samples obtained after the 20th autoshaping session revealed higher plasma corticosterone levels in the CS-US paired group than in the CS-US random control group (n=10). In Experiment 2, rats (n=35) were assessed for basal plasma corticosterone levels 2 weeks prior to autoshaping training. Plasma samples obtained immediately following the first autoshaping session, and prior to the acquisition of lever-press autoshaping CR performance, revealed higher plasma corticosterone levels in the CS-US paired group (n=24) relative to basal levels. This effect was not observed in the CS-US random control group (n=11). Data suggest that corticosterone release is a physiological endocrine Pavlovian CR induced by lever CS-food US pairings during Pavlovian autoshaping procedures, rather than a by-product of autoshaping CR performance. Implications of the link between autoshaping procedures and corticosterone release are discussed.