RESUMO
BACKGROUND: A meta and pooled analysis of published and unpublished case-control studies was performed to evaluate the association of CYP17 (rs743572) and CYP3A4 (rs2740574) polymorphisms and prostate cancer (PCa) in men from the USA, Caribbean, and Africa. METHODS: Eight publications (seven studies) and two unpublished studies for CYP17 included 1,580 subjects (559 cases and 1,021 controls) and eleven publications and three unpublished studies for CYP3A4 included 3,400 subjects (1,429 cases and 1,971 controls). RESULTS: Overall, the CYP17 heterozygous and homozygous variants were not associated with PCa, but they confer a 60% increased risk of PCa in a sub-group analysis restricted to African-American men (T/C + C/C, OR: 1.6, 95% CI: 1.1-2.4). No associations were observed for CYP3A4, overall and in stratified analyses for African-Americans and Africans. The pooled analysis suggests that after adjusting for study, age, PSA, and family history of PCa, CYP17 was associated with PCa for men of African ancestry (Adjusted OR: 3.5, 95% CI: 1.2-10.0). CONCLUSIONS: Our findings suggest that genetic factors involved in the androgen pathway play a role in PCa risk among men of African ancestry.
Assuntos
Negro ou Afro-Americano/genética , Negro ou Afro-Americano/estatística & dados numéricos , Citocromo P-450 CYP3A/genética , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/genética , Esteroide 17-alfa-Hidroxilase/genética , Adulto , Idoso , Região do Caribe/epidemiologia , Estudos de Casos e Controles , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Polimorfismo Genético/genética , Fatores de Risco , Programa de SEER/estatística & dados numéricos , Estados Unidos/epidemiologiaRESUMO
The purpose of this study was to generate stable cell cultures from head and neck squamous cell carcinomas (HNSCC), and retrospectively analyze the factors associated with successful cell line establishment. Fifty-two HNSCC cell lines were isolated from a series of 199 tumors collected between 1992 and 1997 at the University of Pittsburgh Medical Center. Cell lines were characterized at the molecular and cellular level to determine the features associated with cell line formation. Successful cell line formation was dependent on multiple factors, including gene amplification involving chromosomal band 11q13, local and/or regional involvement of lymph nodes, and alcohol usage. The establishment of HNSCC cell lines enriches the resources available for cancer research. Our findings indicate that generation of stable cell lines from HNSCC is biased towards tumors with a poor prognosis. Our 52 stable lines comprise one of the largest series of HNSCC cell lines in the literature, with complete demographic, histopathologic, clinical, and survival data.
Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Adulto , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Feminino , História do Século XVIII , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Prognóstico , Fatores de RiscoRESUMO
Human papillomavirus (HPV) has been associated with head and neck squamous cell carcinomas (HNSCC), especially of the oropharynx, with highest distribution in the tonsils. HPV infection has been associated with improved outcome, although not all the studies show consistent results. The reason for this is not clear. We reviewed all published articles and conducted a meta-analysis on the overall relationship between HPV infection and overall survival (OS) and disease-free survival (DFS) in HNSCC. Patients with HPV-positive HNSCC had a lower risk of dying (meta HR: 0.85, 95% CI: 0.7-1.0), and a lower risk of recurrence (meta HR: 0.62, 95%CI: 0.5-0.8) than HPV-negative HNSCC patients. Site-specific analyses show that patients with HPV-positive oropharyngeal tumours had a 28% reduced risk of death (meta HR: 0.72, 95%CI: 0.5-1.0) in comparison to patients with HPV-negative oropharyngeal tumours. Similar observations were made for DFS (meta HR: 0.51, 95% CI: 0.4-0.7). There was no difference in OS between HPV-positive and negative non-oropharyngeal patients. The observed improved OS and DFS for HPV-positive HNSCC patients is specific to the oropharynx; these tumours may have a distinct etiology from those tumours in non-oropharyngeal sites.