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1.
Cancer ; 124(7): 1342-1349, 2018 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-29266207

RESUMEN

BACKGROUND: Bovine leukemia virus (BLV) and human papillomavirus (HPV) were previously identified in human breast tissue and have been associated with breast cancer in independent studies. The objective of the current study was to test for the presence of BLV and HPV in the same breast tissue specimens to determine whether the viruses were associated with breast cancer either singly or together. METHODS: Archival formalin-fixed paraffin-embedded breast tissue sections from 216 women were received from The University of Texas MD Anderson Cancer Center along with patient diagnosis. In situ polymerase chain reaction and/or DNA hybridization methods were used to detect targeted DNA segments of BLV and HPV. Standard statistical methods were used to calculate age-adjusted odds ratios, attributable risk, and P values for the trend related to the association between presence of a virus and a diagnosis of breast disease. RESULTS: Women diagnosed with breast cancer were significantly more likely to have BLV DNA in their breast tissue compared with women with benign diagnoses and no history of breast cancer. Women with breast pathology classified as premalignant and no history of breast cancer also were found to have an elevated risk of harboring BLV DNA in their breast tissue. HPV status was not associated with malignancy, premalignant breast disease, or the presence of BLV in the breast tissues. CONCLUSIONS: The data from the current study supported previous findings of a significant association between BLV DNA in breast tissue and a diagnosis of breast cancer, but did not demonstrate oncogenic strains of HPV associated with breast cancer or the presence of BLV DNA in breast tissue. The authors believe the findings of the current study contribute to overall knowledge regarding a possible causal role for viruses in human breast cancer. Cancer 2018;124:1342-9. © 2017 American Cancer Society.


Asunto(s)
Neoplasias de la Mama/virología , Carcinoma Ductal de Mama/virología , Carcinoma Lobular/virología , Leucosis Bovina Enzoótica/complicaciones , Virus de la Leucemia Bovina/aislamiento & purificación , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Animales , Neoplasias de la Mama/epidemiología , Carcinoma Ductal de Mama/epidemiología , Carcinoma Lobular/epidemiología , Estudios de Casos y Controles , Bovinos , ADN Viral/genética , Leucosis Bovina Enzoótica/virología , Femenino , Estudios de Seguimiento , Humanos , Virus de la Leucemia Bovina/genética , Persona de Mediana Edad , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Pronóstico , Texas/epidemiología
2.
Breast Cancer Res Treat ; 157(2): 351-361, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27146587

RESUMEN

Among women diagnosed with ductal carcinoma in situ (DCIS), we identified factors associated with local invasive cancer (LIC) and regional/metastatic invasive cancer (RMIC) and provide 10-year risks based on clinically relevant factors. We created a retrospective, population-based cohort of 1492 women with an initial diagnosis of DCIS (1983-1996) treated by lumpectomy alone. Histological and molecular markers (Ki67, ER, PR, COX-2, p16, ERBB2) were collected on DCIS cases with a subsequent tumor (DCIS, LIC, or RMIC) and a subsample of frequency-matched controls without subsequent tumors. Competing risks methods were used to identify factors associated with LIC and RMIC and cumulative incidence methods to estimate 10-year risks for combinations of factors. Median follow-up time was 12.6 years (range 0.5-29.5 years). The overall 10-year risk of LIC (11.9 %) was higher than for RMIC (3.8 %). About half of women with initial DCIS lesions are detected by mammography and p16 negative and have a 10-year risk of LIC of 6.2 % (95 % CI 5.8-6.8 %) and RMIC of 1.2 % (95 % CI 1.1-1.3 %). Premenopausal women whose DCIS lesion was p16 positive or p16 negative and detected by palpation had high 10-year risk of LIC of 23.0 % (95 % CI 19.3-27.4 %). Ten-year risk of RMIC was highest at 22.5 % (95 % CI 13.8-48.1 %) for those positive for p16, COX-2, and ERRB2, and negative for ER, but prevalence of this group is low at 3 %. Ten-year risk of LIC and RMIC is low for the majority diagnosed with DCIS. Combinations of molecular markers and method of detection of initial DCIS lesion can differentiate women at low and high risk of LIC and RMIC.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/cirugía , Carcinoma Intraductal no Infiltrante/diagnóstico , Carcinoma Intraductal no Infiltrante/cirugía , Adulto , Anciano , Neoplasias de la Mama/metabolismo , Carcinoma Intraductal no Infiltrante/metabolismo , Femenino , Humanos , Mamografía , Mastectomía Segmentaria , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento , Adulto Joven
3.
Am J Epidemiol ; 177(1): 75-83, 2013 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-23221727

RESUMEN

Meningioma is an intracranial tumor with few confirmed risk factors. Recent research points to an impact on meningioma risk from factors related to immune function and development, such as allergy, immunoglobulin E, and Varicella infection status. To further explore an association with immune function, the authors assessed individual seroreactivity to meningioma tumor-associated antigens among participants enrolled in a multicenter, population-based US case-control study of meningioma (2006-2009). Serum samples from cases (n = 349) and controls (n = 348) were screened for autoantibody reactivity to 3 proteins identified in previous studies: enolase 1 (ENO1), NK-tumor recognition protein (NKTR), and nuclear mitotic apparatus protein 1 (NUMA1). Case-control differences were not strong overall (adjusted odds ratio (OR)(ENO1 (continuous)) = 1.1, 95% confidence interval (CI): 0.6, 1.9 (P(trend) = 0.3); adjusted OR(NKTR (continuous)) = 1.3, 95% CI: 0.7, 2.4 (P(trend) = 0.02); and adjusted OR(NUMA1 (continuous)) = 1.1, 95% CI: 0.7, 1.8 (P(trend) = 0.06)); however, antibodies to NKTR and NUMA1 were detected at higher levels in cases than in controls, particularly among men (for men, adjusted OR(ENO1 (continuous)) = 1.6, 95% CI: 0.5, 4.7 (P(trend) = 0.24); adjusted OR(NKTR (continuous)) = 4.3, 95% CI: 1.2, 15 (P(trend) = 0.009); and adjusted OR(NUMA1 (continuous)) = 3.6, 95% CI: 1.1, 11 (P(trend) = 0.006)). These results indicate that men with meningioma commonly react with a serologic antimeningioma response; if supported by further research, this finding suggests a distinctive etiology for meningioma in men.


Asunto(s)
Autoanticuerpos/sangre , Meningioma/sangre , Meningioma/inmunología , Adulto , Anciano , Antígenos Nucleares/sangre , Biomarcadores de Tumor/sangre , Proteínas de Ciclo Celular , Proteínas de Unión al ADN/sangre , Eccema/epidemiología , Femenino , Humanos , Hipersensibilidad/epidemiología , Masculino , Meningioma/epidemiología , Persona de Mediana Edad , Proteínas Asociadas a Matriz Nuclear/sangre , Fosfopiruvato Hidratasa/sangre , Receptores Inmunológicos/sangre , Factores Sexuales , Fumar/epidemiología , Factores Socioeconómicos , Proteínas Supresoras de Tumor/sangre , Estados Unidos
4.
Am J Public Health ; 103(10): e73-80, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23948011

RESUMEN

OBJECTIVES: We examined the relationship between genetic ancestry, socioeconomic status (SES), and lung cancer among African Americans and Latinos. METHODS: We evaluated SES and genetic ancestry in a Northern California lung cancer case-control study (1998-2003) of African Americans and Latinos. Lung cancer case and control participants were frequency matched on age, gender, and race/ethnicity. We assessed case-control differences in individual admixture proportions using the 2-sample t test and analysis of covariance. Logistic regression models examined associations among genetic ancestry, socioeconomic characteristics, and lung cancer. RESULTS: Decreased Amerindian ancestry was associated with higher education among Latino control participants and greater African ancestry was associated with decreased education among African lung cancer case participants. Education was associated with lung cancer among both Latinos and African Americans, independent of smoking, ancestry, age, and gender. Genetic ancestry was not associated with lung cancer among African Americans. CONCLUSIONS: Findings suggest that socioeconomic factors may have a greater impact than genetic ancestry on lung cancer among African Americans. The genetic heterogeneity and recent dynamic migration and acculturation of Latinos complicate recruitment; thus, epidemiological analyses and findings should be interpreted cautiously.


Asunto(s)
Negro o Afroamericano , Predisposición Genética a la Enfermedad/genética , Hispánicos o Latinos , Neoplasias Pulmonares/genética , Clase Social , Adulto , Anciano , California , Intervalos de Confianza , Femenino , Técnicas de Genotipaje , Humanos , Modelos Logísticos , Neoplasias Pulmonares/etnología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fumar
5.
Hum Mol Genet ; 19(18): 3652-61, 2010 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-20587604

RESUMEN

Several genome-wide association studies identified the chr15q25.1 region, which includes three nicotinic cholinergic receptor genes (CHRNA5-B4) and the cell proliferation gene (PSMA4), for its association with lung cancer risk in Caucasians. A haplotype and its tagging single nucleotide polymorphisms (SNPs) encompassing six genes from IREB2 to CHRNB4 were most strongly associated with lung cancer risk (OR = 1.3; P < 10(-20)). In order to narrow the region of association and identify potential causal variations, we performed a fine-mapping study using 77 SNPs in a 194 kb segment of the 15q25.1 region in a sample of 448 African-American lung cancer cases and 611 controls. Four regions, two SNPs and two distinct haplotypes from sliding window analyses, were associated with lung cancer. CHRNA5 rs17486278 G had OR = 1.28, 95% CI 1.07-1.54 and P = 0.008, whereas CHRNB4 rs7178270 G had OR = 0.78, 95% CI 0.66-0.94 and P = 0.008 for lung cancer risk. Lung cancer associations remained significant after pack-year adjustment. Rs7178270 decreased lung cancer risk in women but not in men; gender interaction P = 0.009. For two SNPs (rs7168796 A/G and rs7164594 A/G) upstream of PSMA4, lung cancer risks for people with haplotypes GG and AA were reduced compared with those with AG (OR = 0.56, 95% CI 0.38-0.82; P = 0.003 and OR = 0.73, 95% CI 0.59-0.90, P = 0.004, respectively). A four-SNP haplotype spanning CHRNA5 (rs11637635 C, rs17408276 T, rs16969968 G) and CHRNA3 (rs578776 G) was associated with increased lung cancer risk (P = 0.002). The identified regions contain SNPs predicted to affect gene regulation. There are multiple lung cancer risk loci in the 15q25.1 region in African-Americans.


Asunto(s)
Negro o Afroamericano/genética , Cromosomas Humanos Par 15/genética , Predisposición Genética a la Enfermedad , Neoplasias Pulmonares/genética , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Mapeo Cromosómico , Femenino , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Proteínas del Tejido Nervioso/genética , Polimorfismo de Nucleótido Simple , Receptores Nicotínicos/genética , Fumar/genética , Adulto Joven
6.
Cancer ; 118(5): 1212-20, 2012 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-21823105

RESUMEN

BACKGROUND: Human papillomavirus (HPV) has been proposed as an etiologic agent of breast cancer based on numerous reports of high-risk (oncogenic) HPV types in malignant breast tissues. However, most of those studies used standard and nested solution polymerase chain reaction (PCR) techniques, both of which are disadvantaged by vulnerability to laboratory contamination from positive control DNA and the inability to localize the signal to a specific cell type. To overcome these drawbacks, the authors of this report explored the use of in situ molecular methods of viral detection to reassess the frequency of HPV in malignant breast tissue. METHODS: In situ hybridization (ISH) was used with probes that were specific for the capsid region of 12 oncogenic HPV types, and in situ PCR (IS-PCR) was used with primers that were specific for the capsid region of HPV-16, which is the most common oncogenic HPV type. These methods were resistant to molecular contamination and allowed identification of the positive cell type. The specimens examined were malignant tissues from patients with 70 breast cancer patients at The University of Texas M. D. Anderson Cancer Center in Houston, Texas. RESULTS: HPV was observed in 4 of 70 specimens (5.7%) using ISH and in 2 of 70 specimens (2.9%) of specimens using IS-PCR. Concordance between the 2 methods was high for negative specimens; both methods yielded negative results in 66 of 70 specimens (94.3%). However, there was no concordance for the few positive specimens, probably because of differences in sensitivity and the targeted HPV types. CONCLUSIONS: Oncogenic (high-risk) HPV types were present in malignant breast epithelium very infrequently and, thus, may be causative agents of only a relatively small proportion of all breast cancers.


Asunto(s)
Alphapapillomavirus/aislamiento & purificación , Neoplasias de la Mama/virología , Mama/virología , Carcinoma Ductal de Mama/virología , Hibridación in Situ/métodos , Técnicas de Diagnóstico Molecular/métodos , Adulto , Anciano , Alphapapillomavirus/genética , Mama/patología , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/etiología , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/epidemiología , Carcinoma Ductal de Mama/etiología , Carcinoma Ductal de Mama/patología , Línea Celular Tumoral , ADN Viral/aislamiento & purificación , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa/métodos
7.
Breast Cancer Res Treat ; 132(1): 267-74, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22042367

RESUMEN

Epstein-Barr virus (EBV) has been proposed as a possible etiological agent of breast cancer based on 21 reports of EBV in malignant breast tissues. Most of these studies used standard and nested solution polymerase chain reaction (PCR) techniques, both disadvantaged by susceptibility to contamination from laboratory EBV, and the inability to localize the signal to a specific cell type. To avoid these issues, we used in situ molecular methods of viral detection to reassess the frequency of EBV in malignant breast tissue. We used a commercial in situ hybridization (ISH) system with an EBER genome target, and a non-commercial in situ PCR (IS-PCR) method using primers specific for the BamH1 region. The assays were performed on malignant breast tissue sections from 70 breast cancer patients at the M. D. Anderson Cancer Center, Houston, TX. EBV was found in mammary epithelial cells, the cell type from which most breast cancers arise, in 2/70 (2.9%) of specimens using IS-PCR and in none of the specimens using ISH. Based on these findings that EBV was present in human mammary epithelial cells so infrequently, it is unlikely to play a causative role in most types of breast cancer.


Asunto(s)
Neoplasias de la Mama/virología , Carcinoma Ductal de Mama/virología , Carcinoma Intraductal no Infiltrante/virología , Carcinoma Lobular/virología , Epitelio/virología , Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4 , Adulto , Anciano , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Lobular/patología , Femenino , Humanos , Hibridación in Situ , Leucocitos/virología , Persona de Mediana Edad
8.
Int J Cancer ; 129(8): 1932-9, 2011 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-21520030

RESUMEN

Meningioma, the most frequent tumor in the central nervous system, has few recognized risk factors. We explored the role of allergies in a population-based case-control consortium study of meningioma in five geographic areas. We also studied serum levels of a marker of atopic allergy (IgE) in a subset of study participants, a first for a study on meningioma. Participants (N = 1,065) with surgically resected, pathologically confirmed meningioma and controls (N = 634) selected via random-digit dialing were recruited and interviewed. Cases were less likely than controls to report history of physician-diagnosed allergy [odds ratio (OR) = 0.64; 95% confidence interval (95% CI): 0.51-0.80]. Also, cases (N = 295) had lower total serum IgE than controls [N = 192; OR = 0.85, 95% CI: 0.75-0.98 for each unit of Ln(IgE)]. Similar to glioma and cancers at several other sites, meningioma appears to have an inverse relationship with history of allergies and a biomarker of atopic allergy. As some common opposing predisposition or developmental processes for allergy and meningioma may exist, further research into immune processes that can affect the incidence and natural history of meningioma is warranted.


Asunto(s)
Hipersensibilidad/epidemiología , Inmunoglobulina E/sangre , Neoplasias Meníngeas/inmunología , Meningioma/inmunología , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad
9.
Am J Ind Med ; 54(11): 811-8, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21882217

RESUMEN

OBJECTIVES: Considerable controversy surrounds the carcinogenic potential of asphalt and tar. Since minority individuals may have had relatively high historical exposures, we investigated asphalt and tar exposure and lung cancer risk among African Americans and Latino Americans. METHODS: We conducted a case-control study of lung cancer among African Americans and Latino Americans in the San Francisco Bay area (422 cases, 894 controls). A questionnaire was used to obtain detailed work histories and exposure information. Self-reported exposure to asphalt and tar as well as other factors (e.g., smoking, automobile exhaust, and asbestos) were evaluated as predictors of lung cancer risk. Potential effect modification by cytochrome P450 (CYP) 1A1 was also explored. RESULTS: Self-reported duration of exposure to asphalt and tar was associated with a statistically significant excess risk of lung cancer in the overall population (OR: 1.11, 95% CI: 1.01-1.22), evaluating risk per year of exposure. Years of exposure to automobile exhaust (OR: 1.02, 95% CI: 1.00-1.05) and asbestos (OR: 1.04, 95% CI: 1.02-1.06) were also associated with statistically significant elevations in risk. In Latino Americans, the lung cancer risks associated with polycyclic aromatic hydrocarbon-related exposures were consistently higher in the CYP1A1 wild-type subjects as compared to the variant genotype subjects, and the interaction was statistically significant for smoking and the CYP1A1 M2 polymorphism (P-value(interaction) = 0.02). CONCLUSIONS: These data are consistent with the literature suggesting that exposure to asphalt and tar may increase risk of lung cancer. However, it was not possible to separate the effects and asphalt and tar in this study.


Asunto(s)
Hidrocarburos/toxicidad , Neoplasias Pulmonares/epidemiología , Grupos Minoritarios/estadística & datos numéricos , Exposición Profesional/efectos adversos , Hidrocarburos Policíclicos Aromáticos/toxicidad , Negro o Afroamericano/estadística & datos numéricos , Anciano , Estudios de Casos y Controles , Intervalos de Confianza , Femenino , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Modelos Logísticos , Neoplasias Pulmonares/etiología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , San Francisco/epidemiología , Encuestas y Cuestionarios
10.
Carcinogenesis ; 30(1): 78-87, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19029194

RESUMEN

Base excision repair (BER) is the primary DNA damage repair mechanism for repairing small base lesions resulting from oxidation and alkylation damage. This study examines the association between 24 single-nucleotide polymorphisms (SNPs) belonging to five BER genes (XRCC1, APEX1, PARP1, MUTYH and OGG1) and lung cancer among Latinos (113 cases and 299 controls) and African-Americans (255 cases and 280 controls). The goal was to evaluate the differences in genetic contribution to lung cancer risk by ethnic groups. Analyses of individual SNPs and haplotypes were performed using unconditional logistic regressions adjusted for age, sex and genetic ancestry. Four SNPs among Latinos and one SNP among African-Americans were significantly (P < 0.05) associated with either risk of all lung cancer or non-small cell lung cancer (NSCLC). However, only the association between XRCC1 Arg399Gln (rs25487) and NSCLC among Latinos (odds ratio associated with every copy of Gln = 1.52; 95% confidence interval: 1.01-2.28) had a false-positive report probability of <0.5. Arg399Gln is a SNP with some functional evidence and has been shown previously to be an important SNP associated with lung cancer, mostly for Asians. Since the analyses were adjusted for genetic ancestry, the observed association between Arg399Gln and NSCLC among Latinos is unlikely to be confounded by population stratification; however, this result needs to be confirmed by additional studies among the Latino population. This study suggests that there are genetic differences in the association between BER pathway and lung cancer between Latinos and African-Americans.


Asunto(s)
Población Negra , Reparación del ADN , Hispánicos o Latinos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/genética , Anciano , Femenino , Predisposición Genética a la Enfermedad , Humanos , Neoplasias Pulmonares/etnología , Masculino , Persona de Mediana Edad , Factores de Riesgo , San Francisco/epidemiología
11.
Int J Cancer ; 123(9): 2095-104, 2008 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-18709642

RESUMEN

Few studies on the association between nucleotide excision repair (NER) variants and lung cancer risk have included Latinos and African Americans. We examine variants in 6 NER genes (ERCC2, ERCC4, ERCC5, LIG1, RAD23B and XPC) in association with primary lung cancer risk among 113 Latino and 255 African American subjects newly diagnosed with primary lung cancer from 1998 to 2003 in the San Francisco Bay Area and 579 healthy controls (299 Latinos and 280 African Americans). Individual single nucleotide polymorphism and haplotype analyses, multifactor dimensionality reduction (MDR) and principal components analysis (PCA) were performed to assess the association between 6 genes in the NER pathway and lung cancer risk. Among Latinos, ERCC2 haplotype CGA (rs238406, rs11878644, rs6966) was associated with reduced lung cancer risk [odds ratio (OR) of 0.65 and 95% confidence interval (CI): 0.44-0.97], especially among nonsmokers (OR = 0.29; 95% CI: 0.12-0.67). From MDR analysis, in Latinos, smoking and 3 SNPs (ERCC2 rs171140, ERCC5 rs17655 and LIG1 rs20581) together had a prediction accuracy of 67.4% (p = 0.001) for lung cancer. Among African Americans, His/His genotype of ERCC5 His1104Asp (rs17655) was associated with increased lung cancer risk (OR = 1.78; 95% CI: 1.09-2.91), and LIG1 haplotype GGGAA (rs20581, rs156641, rs3730931, rs20579 and rs439132) was associated with reduced lung cancer risk (OR = 0.61; 95% CI: 0.42-0.88). Our study suggests different elements of the NER pathway may be important in the different ethnic groups resulting either from different linkage relationship, genetic backgrounds and/or exposure histories.


Asunto(s)
Negro o Afroamericano/genética , Reparación del ADN/genética , Hispánicos o Latinos/genética , Neoplasias Pulmonares/genética , Anciano , ADN Ligasa (ATP) , ADN Ligasas/genética , Proteínas de Unión al ADN/genética , Endonucleasas/genética , Femenino , Haplotipos , Humanos , Neoplasias Pulmonares/etnología , Neoplasias Pulmonares/etiología , Masculino , Persona de Mediana Edad , Proteínas Nucleares/genética , Polimorfismo de Nucleótido Simple , Análisis de Componente Principal , Riesgo , Fumar/efectos adversos , Factores de Transcripción/genética , Proteína de la Xerodermia Pigmentosa del Grupo D/genética
12.
Am J Epidemiol ; 168(9): 1035-46, 2008 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-18791191

RESUMEN

A variety of methods are available for estimating genetic admixture proportions in populations; however, few investigators have conducted detailed comparisons using empirical data. The authors characterized admixture proportions among self-identified African Americans (n = 535) and Latinos (n = 412) living in the San Francisco Bay Area who participated in a lung cancer case-control study (1998-2003). Individual estimates of genetic ancestry based on 184 informative markers were obtained from a Bayesian approach and 2 maximum likelihood approaches and were compared using descriptive statistics, Pearson correlation coefficients, and Bland-Altman plots. Case-control differences in individual admixture proportions were assessed using 2-sample t tests and logistic regression analysis. Results indicated that Bayesian and frequentist approaches to estimating admixture provide similar estimates and inferences. No difference was observed in admixture proportions between African-American cases and controls, but Latino cases and controls significantly differed according to Amerindian and European genetic ancestry. Differences in admixture proportions between Latino cases and controls were not unexpected, since cases were more likely to have been born in the United States. Genetic admixture proportions provide a quantitative measure of ancestry differences among Latinos that can be used in analyses of genetic risk factors.


Asunto(s)
Teorema de Bayes , Negro o Afroamericano/genética , Hispánicos o Latinos/genética , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/genética , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Métodos Epidemiológicos , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , San Francisco/epidemiología
13.
Cancer Epidemiol Biomarkers Prev ; 17(6): 1368-73, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18559551

RESUMEN

Glioma is a complex disease that is unlikely to result from the effect of a single gene. Genetic analysis at the pathway level involving multiple genes may be more likely to capture gene-disease associations than analyzing genes one at a time. The current pilot study included 112 Caucasians with glioblastoma multiforme and 112 Caucasian healthy controls frequency matched to cases by age and gender. Subjects were genotyped using a commercially available (ParAllele/Affymetrix) assay panel of 10,177 nonsynonymous coding single-nucleotide polymorphisms (SNP) spanning the genome known at the time the panel was constructed. For this analysis, we selected 10 pathways potentially involved in gliomagenesis that had SNPs represented on the panel. We performed random forests (RF) analyses of SNPs within each pathway group and logistic regression to assess interaction among genes in the one pathway for which the RF prediction error was better than chance and the permutation P < 0.10. Only the DNA repair pathway had a better than chance classification of case-control status with a prediction error of 45.5% and P = 0.09. Three SNPs (rs1047840 of EXO1, rs12450550 of EME1, and rs799917 of BRCA1) of the DNA repair pathway were identified as promising candidates for further replication. In addition, statistically significant interactions (P < 0.05) between rs1047840 of EXO1 and rs799917 or rs1799966 of BRCA1 were observed. Despite less than complete inclusion of genes and SNPs relevant to glioma and a small sample size, RF analysis identified one important biological pathway and several SNPs potentially associated with the development of glioblastoma.


Asunto(s)
Neoplasias Encefálicas/genética , Proteínas Cromosómicas no Histona/genética , Proteínas de Unión al ADN/genética , Perfilación de la Expresión Génica/métodos , Predisposición Genética a la Enfermedad , Glioblastoma/genética , Polimorfismo de Nucleótido Simple , Estudios de Casos y Controles , Factor 1 de Ensamblaje de la Cromatina , Femenino , Genotipo , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Fenotipo , Proyectos Piloto , Riesgo , Población Blanca/genética
14.
BMC Cancer ; 8: 75, 2008 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-18366688

RESUMEN

BACKGROUND: Past studies have shown that women with abnormal cytology or epithelial cells in nipple aspirate fluid (NAF) have an increased relative risk (RR) of breast cancer when compared to women from whom NAF was attempted but not obtained (non-yielders). This study analyzed NAF results from a group of women seen in a breast clinic between 1970-1991 (N = 2480). Our analysis presented here is an aggregate of two sub-groups: women with questionnaire data (n = 712) and those with NAF visits beginning in 1988 (n = 238), the year in which cancer case information was uniformly collected in California. METHODS: Cytological classification was determined for a group of 946 women using the most abnormal epithelial cytology observed in fluid specimens. Breast cancer incidence and mortality status was determined through June 2006 using data from the California Cancer Registry, California Vital Statistics and self-report. We estimated odd ratios (ORs) for breast cancer using logistic regression analysis, adjusting for age. We analyzed breast cancer risk related to abnormality of NAF cytology using non-yielders as the referent group and breast cancer risk related to the presence or absence of epithelial cells in NAF, using non-yielders/fluid without epithelial cells as the referent group. RESULTS: Overall, 10% (93) of the 946 women developed breast cancer during the follow-up period. Age-adjusted ORs and 95% confidence intervals (C.I.) compared to non-yielders were 1.4 (0.3 to 6.4), 1.7 (0.9 to 3.5), and 2.0 (1.1 to 3.6) for women with fluid without epithelial cells, normal epithelial cells and hyperplasia/atypia, respectively. Comparing the presence or absence of epithelial cells in NAF, women with epithelial cells present in NAF were more likely to develop breast cancer than non-yielders or women with fluid without epithelial cells (RR = 1.9, 1.2 to 3.1). CONCLUSION: These results support previous findings that 1) women with abnormal epithelial cells in NAF have an increased risk of breast cancer when compared to non-yielders or women with normal epithelial cells in NAF and 2) women with epithelial cells present in NAF have an increased risk of breast cancer when compared to non-yielders or women who had NAF without epithelial cells present.


Asunto(s)
Líquidos Corporales/metabolismo , Neoplasias de la Mama/metabolismo , Células Epiteliales/metabolismo , Pezones/metabolismo , Adulto , Anciano , Neoplasias de la Mama/patología , Células Epiteliales/patología , Epitelio/patología , Femenino , Humanos , Persona de Mediana Edad , Oportunidad Relativa , Estudios Prospectivos , Análisis de Regresión , Riesgo , Encuestas y Cuestionarios
15.
Clin Cancer Res ; 13(1): 197-205, 2007 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-17200355

RESUMEN

PURPOSE: Our aim was to discover possible inherited factors associated with glioblastoma age at diagnosis and survival. Although new genotyping technologies allow greatly expanded exploration of such factors, they pose many challenges. EXPERIMENTAL DESIGN: In this pilot study, we (a) genotyped 112 newly diagnosed glioblastoma patients ascertained through a population-based study (group 1) with the ParAllele assay panel of approximately 10,000 nonsynonymous coding single-nucleotide polymorphisms (SNP), (b) used several statistical and bioinformatic techniques to identify 17 SNPs potentially related to either glioblastoma age at diagnosis or survival, and (c) genotyped 16 of these SNPs using conventional PCR methods in an independent group of 195 glioblastoma patients (group 2). RESULTS: In group 2, only one of the 16 SNPs, rs8057643 (located on 16p13.2), was significantly associated with glioblastoma age at diagnosis (nominal P = 0.0017; Bonferroni corrected P = 0.054). Median ages at diagnosis for those with 0, 1, or 2 T alleles were 66, 57, and 59 years in group 1 and 64, 57, and 55 years in group 2 (combined P = 0.001). Furthermore, Cox regression analyses of time to death with number of T alleles adjusted for gender and patient group yielded a hazard ratio of 0.82 (95% confidence interval, 0.68-0.98; P = 0.03). CONCLUSIONS: Although limited by a relatively small sample size, this pilot study, using well-characterized, unambiguous disease characteristics, illustrates the necessity of independent replication owing to the likelihood of false positives. Several other challenges are discussed, including attempts to incorporate information on the potential functional importance of SNPs in genome-disease association studies.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Genoma , Glioblastoma/genética , Glioblastoma/patología , Polimorfismo de Nucleótido Simple , Factores de Edad , Edad de Inicio , Anciano , Alelos , Codón , Codón de Terminación , Femenino , Genotipo , Glioblastoma/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Resultado del Tratamiento
16.
Cancer Res ; 66(8): 4531-41, 2006 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-16618782

RESUMEN

In population-based glioma patients, we examined survival in relation to potentially pertinent constitutive polymorphisms, serologic factors, and tumor genetic and protein alterations in epidermal growth factor receptor (EGFR), MDM2, and TP53. Subjects were newly diagnosed adults residing in the San Francisco Bay Surveillance Epidemiology and End Results Area during 1991 to 1994 and 1997 to 1999 with central neuropathology review (n = 873). Subjects provided blood for serologic studies of IgE and IgG to four herpes viruses and constitutive specimens for genotyping 22 polymorphisms in 13 genes (n = 471). We obtained 595 of 697 astrocytic tumors for marker studies. We determined treatments, vital status, and other factors using registry, interview, medical record, and active follow-up data. Cox regressions for survival were adjusted for age, gender, ethnicity, study series, resection versus biopsy only, radiation, and chemotherapy. Using a stringent P < 0.001, glioma survival was associated with ERCC1 C8092A [hazard ratio (HR), 0.72; 95% confidence limits (95% CL), 0.60-0.86; P = 0.0004] and GSTT1 deletion (HR, 1.64; 95% CL, 1.25-2.16; P = 0.0004); glioblastoma patients with elevated IgE had 9 months longer survival than those with normal or borderline IgE levels (HR, 0.62; 95% CL, 0.47-0.82; P = 0.0007), and EGFR expression in anaplastic astrocytoma was associated with nearly 3-fold poorer survival (HR, 2.97; 95% CL, 1.70-5.19; P = 0.0001). Based on our and others' findings, we recommend further studies to (a) understand relationships of elevated IgE levels and other immunologic factors with improved glioblastoma survival potentially relevant to immunologic therapies and (b) determine which inherited ERCC1 variants or other variants in the 19q13.3 region influence survival. We also suggest that tumor EGFR expression be incorporated into clinical evaluation of anaplastic astrocytoma patients.


Asunto(s)
Astrocitoma/genética , Receptores ErbB/biosíntesis , Glioblastoma/genética , Inmunoglobulina E/sangre , Astrocitoma/sangre , Astrocitoma/metabolismo , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Receptores ErbB/genética , Glioblastoma/sangre , Glioblastoma/metabolismo , Humanos , Persona de Mediana Edad , Polimorfismo Genético
17.
BMC Cancer ; 6: 148, 2006 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-16749939

RESUMEN

BACKGROUND: Increasing evidence from epidemiologic studies suggest that oxidative stress may play a role in adult glioma. In addition to dietary antioxidants, antioxidant and weak estrogenic properties of dietary phytoestrogens may attenuate oxidative stress. Our hypothesis is that long-term consumption of dietary antioxidants and phytoestrogens such as genistein, daidzein, biochanin A, formononetin, matairesinol, secoisolariciresinol and coumestrol, may reduce the risk of adult glioma. METHODS: Using unconditional logistic regression models, we compared quartiles of consumption for several specific antioxidants and phytoestrogens among 802 adult glioma cases and 846 controls from two study series from the San Francisco Bay Area Adult Glioma Study, 1991-2000, controlling for vitamin supplement usage, age, socioeconomic status, gender, ethnicity and total daily calories. For cases, dietary information was either self-reported or reported by a proxy. For controls, dietary information was self-reported. Gender- and series-specific quartiles of average daily nutrient intake, estimated from food-frequency questionnaires, were computed from controls. RESULTS: Significant p-values (trend test) were evaluated using significance levels of either 0.05 or 0.003 (the Bonferroni corrected significance level equivalent to 0.05 adjusting for 16 comparisons). For all cases compared to controls, statistically significant inverse associations were observed for antioxidant index (p < 0.003), carotenoids (alpha- and beta-carotene combined, p < 0.05), daidzein (p = 0.003), matairesinol (p < 0.05), secoisolariciresinol (p < 0.003), and coumestrol (p < 0.003). For self-reported cases compared to controls, statistically significant inverse associations were observed for antioxidant index (p < 0.05) and daidzein (p < 0.05). CONCLUSION: Our results support inverse associations of glioma with higher dietary antioxidant index and with higher intake of certain phytoestrogens, especially daidzein.


Asunto(s)
Antioxidantes/farmacología , Neoplasias Encefálicas/prevención & control , Dieta , Glioma/prevención & control , Fitoestrógenos/farmacología , Adulto , Anciano , Neoplasias Encefálicas/epidemiología , Estudios de Casos y Controles , Femenino , Glioma/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estado Nutricional , Estrés Oxidativo , Análisis de Regresión , San Francisco/epidemiología
18.
BMC Womens Health ; 6: 15, 2006 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-17044938

RESUMEN

BACKGROUND: The search for biologic endpoints and biomarkers in the study of breast cancer risk assessment and risk reduction strategies has led to an interest in obtaining cytologic information and other biomarkers from nipple aspirate fluid (NAF). METHODS: This descriptive study examined factors associated with an increased ability to obtain NAF in a cohort of 3043 women between the ages of 15 and 89 years of age. The majority of women were between the ages of 30-49 (N = 1529/50.2%). Variables examined in relation to obtaining fluid include: age, marital status, age at menarche, menopausal status, a history of pregnancy, a history of breast-feeding, estrogen use, oral contraceptive use, endocrine disorders and tranquilizer use. RESULTS: On average, women from whom breast fluid was obtained were younger than women from whom breast fluid was attempted but not obtained (mean = 41.9 years versus 46.5 years, p < 0.0001). In unadjusted and age-adjusted comparisons, being married, a history of pregnancy, younger age at menarche (12 years of age or younger), tranquilizer use, oral contraceptive pill (OCP) use and endocrine problems were associated with an increased ability to obtain breast fluid. Post-menopausal status and exogenous estrogen use were associated with a decreased ability to obtain breast fluid. After age-adjustment, oral contraceptive use was no longer significantly associated with an increased ability to obtain fluid and post-menopausal status was no longer associated with a decreased ability to obtain breast fluid. After multivariate adjustment, age, being married, a history of pregnancy, tranquilizer use and a history of endocrine problems remained positively associated with the ability to obtain breast fluid. In addition, menopausal women who took estrogen were less likely to yield fluid than premenopausal women. CONCLUSION: Four variables (being married, history of pregnancy, tranquilizer use and endocrine disorders) remained positively associated with the ability to obtain NAF in all analyses. A younger age was consistently associated with a greater ability to obtain NAF in this and other studies.

19.
Lung Cancer ; 98: 33-42, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27393504

RESUMEN

OBJECTIVES: Genome-wide association studies (GWAS) of lung cancer have identified regions of common genetic variation with lung cancer risk in Europeans who smoke and never-smoking Asian women. This study aimed to conduct a GWAS in African Americans, who have higher rates of lung cancer despite smoking fewer cigarettes per day when compared with Caucasians. This population provides a different genetic architecture based on underlying African ancestry allowing the identification of new regions and exploration of known regions for finer mapping. MATERIALS AND METHODS: We genotyped 1,024,001 SNPs in 1737 cases and 3602 controls in stage 1, followed by a replication phase of 20 SNPs (p<1.51×10(-5)) in an independent set of 866 cases and 796 controls in stage 2. RESULTS AND CONCLUSION: In the combined analysis, we confirmed two loci to be associated with lung cancer that achieved the threshold of genome-wide significance: 15q25.1 marked by rs2036527 (p=1.3×10(-9); OR=1.32; 95% CI=1.20-1.44) near CHRNA5, and 5p15.33 marked by rs2853677 (p=2.8×10(-9); OR=1.28; 95% CI=1.18-1.39) near TERT. The association with rs2853677 is driven by the adenocarcinoma subtype of lung cancer (p=1.3×10(-8); OR=1.37; 95% CI=1.23-1.54). No SNPs reached genome-wide significance for either of the main effect models examining smoking - cigarettes per day and current or former smoker. Our study was powered to identify strong risk loci for lung cancer in African Americans; we confirmed results previously reported in African Americans and other populations for two loci near plausible candidate genes, CHRNA5 and TERT, on 15q25.1 and 5p15.33 respectively, are associated with lung cancer. Additional work is required to map and understand the biological underpinnings of the strong association of these loci with lung cancer risk in African Americans.


Asunto(s)
Negro o Afroamericano/genética , Cromosomas Humanos Par 15 , Cromosomas Humanos Par 5 , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/genética , Sitios de Carácter Cuantitativo , Estudios de Casos y Controles , Humanos , Polimorfismo de Nucleótido Simple , Vigilancia de la Población
20.
Neuro Oncol ; 7(4): 495-507, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16212814

RESUMEN

ERCC2 and ERCC1 are important in DNA nucleotide excision repair and lie on chromosome 19q13.3 near a putative glioma suppressor region. We genotyped constitutive variants ERCC1 C8092A and ERCC2 K751Q and R156R in approximately 450 adults with glioma and 500 controls from two independent population-based series, uniformly reviewed patients' tumors to determine histopathologic category, and determined a variety of tumor markers among astrocytic tumors. Odds ratios (ORs) for glioblastoma for those carrying two ERCC1 A alleles versus none or one were 1.67 in series 1 and 1.64 in series 2, which yielded a combined OR of 1.67 (95% CI, 0.93-3.02; P = 0.09), adjusted for age, gender, ethnicity, and series. Odds ratios for the ERCC2 variants were not consistently elevated or reduced for the two series in all cases versus controls. However, among whites, for those with ERCC2 K751Q genotype QQ versus QK/KK, the OR for nonglioblastoma histologies versus controls was 1.82 (95% CI, 0.97-3.44; P = 0.06). Also, among whites, glioma patients were significantly more likely than controls to be homozygous for variants in both ERCC1 C8092A and ERCC2 K751Q (OR, 3.2; 95% CI, 1.1-9.3). Given the numbers of comparisons made, these findings could be due to chance. However, the results might warrant clarification in additional series in conjunction with the nearby putative glioma suppressor genes (GLTSCR1 and GLTSCR2).


Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias Encefálicas/genética , Proteínas de Unión al ADN/genética , Endonucleasas/genética , Glioma/genética , Polimorfismo Genético , Neoplasias Encefálicas/epidemiología , Femenino , Frecuencia de los Genes , Glioma/epidemiología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Factores de Riesgo , Población Blanca
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