RESUMO
This Review summarizes the cumulative results of the National Cancer Institute Clinical Genetics Branch Multidisciplinary Etiologic Study of Familial Testicular Germ Cell Tumors (FTGCT). Initiated 12 years ago, this protocol enrolled 724 subjects from 147 unrelated families with either ≥2 affected men (n = 90) with TGCT or a proband with bilateral TGCT and a negative family history for this cancer (n = 57). Data were collected directly from 162 subjects evaluated at the NIH Clinical Center, and 562 subjects provided information from their home communities (Field Cohort). The primary study aims included (i) ascertaining, enrolling eligible FTGCT kindred, (ii) characterizing the clinical phenotype of multiple-case families, (iii) identifying the underlying genetic mechanism for TGCT susceptibility in families, (iv) evaluating counseling, psychosocial, and behavioral issues resulting from membership in an FTGCT family, and (v) creating an annotated biospecimen repository to permit subsequent translational research studies. Noteworthy findings include (i) documenting the epidemiologic similarities between familial and sporadic TGCT, (ii) demonstrating significantly younger age-at-diagnosis for familial vs. sporadic TGCT, (iii) absence of a dysmorphic phenotype in affected family members, (iv) shifting the focus of gene discovery from a search for rare, highly penetrant susceptibility variants to the hypothesis that multiple, more common, lower penetrance genes underlie TGCT genetic risk, (v) implicating testicular microlithiasis in FTGCT risk, and (vi) observing that aberrant methylation may contribute to FTGCT risk. A clinically based, biospecimen-intensive, multidisciplinary research strategy has provided novel, valuable insights into the etiology of FTGCT, and created a research resource which will support FTGCT clinical and laboratory studies for years to come.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Testiculares/genética , Bancos de Espécimes Biológicos , Aconselhamento Genético , Predisposição Genética para Doença , Testes Genéticos , Hereditariedade , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/terapia , Linhagem , Fenótipo , Medicina de Precisão , Prognóstico , Projetos de Pesquisa , Medição de Risco , Fatores de Risco , Neoplasias Testiculares/patologia , Neoplasias Testiculares/terapiaRESUMO
BACKGROUND: A positive family history is a known risk factor for several cancers; thus, obtaining a thorough family cancer history is essential in cancer risk evaluation and prevention management. METHODS: The Family Health Study, a telephone survey in Connecticut, was conducted in 2001. A total of 1,019 participants with demographic information and family cancer history were included in this study. Prevalence of a positive family history of breast, colorectal, prostate, and lung cancer for first- and second-degree relatives was estimated. Logistic regression was used to compare prevalence by demographic factors. RESULTS: A positive family history among first-degree relatives was reported by 10.9% (95% Confidence Interval, CI = 8.8-13.3) of respondents for breast cancer, 5.1% (95% CI = 3.9-6.7) for colorectal cancer, 7.0% (95% CI = 5.2-9.4) for prostate cancer, and 6.4% (95% CI = 4.9-8.3) for lung cancer. The reported prevalence of family history of specific cancers varied by sex, age and race/ethnicity of the respondents. CONCLUSION: Family history prevalence for 4 of the most common adult solid tumors is substantial and the reported prevalence varied by respondent characteristics. Additional studies are needed to evaluate tools to promote accurate reporting of family history of cancer.
Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias Colorretais/epidemiologia , Predisposição Genética para Doença , Neoplasias Pulmonares/epidemiologia , Anamnese/estatística & dados numéricos , Neoplasias da Próstata/epidemiologia , Adulto , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Neoplasias Colorretais/genética , Neoplasias Colorretais/prevenção & controle , Saúde da Família , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/prevenção & controle , Masculino , Pessoa de Meia-Idade , Prevalência , Neoplasias da Próstata/genética , Neoplasias da Próstata/prevenção & controle , Fatores de Risco , Inquéritos e Questionários , Estados Unidos/epidemiologiaRESUMO
The close functional relationship between p53 and the breast cancer susceptibility genes BRCA1 and BRCA2 has promoted the investigation of various polymorphisms in the p53 gene as possible risk modifiers in BRCA1/2 mutation carriers. Specifically, two polymorphisms in p53, c.97-147ins16bp and p.Arg72Pro have been analysed as putative breast cancer susceptibility variants, and it has been recently reported that a p53 haplotype combining the absence of the 16-bp insertion and the presence of proline at codon 72 (No Ins-72Pro) was associated with an earlier age at the onset of the first primary tumour in BRCA2 mutation carriers in the Spanish population. In this study, we have evaluated this association in a series of 2932 BRCA1/2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2.
