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1.
Endocrinol Metab Clin North Am ; 52(4): 705-717, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37865483

RESUMEN

Pituitary adenomas have been increasingly detected in recent years, especially in the older population. Black patients have a higher incidence than other racial groups. In patients with functioning tumors, presentation and comorbidities are influenced by age and sex, whereas the impact of ethnoracial background is unclear. Active surveillance recommendation and surgery refusal disproportionally affect Black and older patients. The likelihood of surgery at high-volume centers is lower for patients of Black or Hispanic background, uninsured or with lower socioeconomic status. Multicentric studies are necessary to delineate the influence of sociodemographic factors according to the adenoma type and to address the causes of health care disparities.


Asunto(s)
Adenoma , Neoplasias Hipofisarias , Humanos , Adenoma/diagnóstico , Adenoma/epidemiología , Adenoma/etnología , Adenoma/cirugía , Hispánicos o Latinos/estadística & datos numéricos , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/epidemiología , Neoplasias Hipofisarias/etnología , Neoplasias Hipofisarias/cirugía , Factores Sociodemográficos , Negro o Afroamericano/estadística & datos numéricos , Pacientes no Asegurados/estadística & datos numéricos , Estatus Socioeconómico Bajo
2.
Int J Cancer ; 153(12): 1978-1987, 2023 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-37555819

RESUMEN

Evidence suggests that aspirin use reduces the occurrence of colorectal neoplasia. Few studies have investigated the association among Black Americans, who are disproportionately burdened by the disease. We assessed aspirin use in relation to colorectal adenoma among Black women. The Black Women's Health Study is a prospective cohort of self-identified Black American women established in 1995. Participants reported regular aspirin use on baseline and follow-up questionnaires. Beginning in 1999, participants reported undergoing a colonoscopy or sigmoidoscopy, the only procedures through which colorectal adenomas can be diagnosed. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between aspirin use and colorectal adenoma among 34 397 women who reported at least 1 colonoscopy or sigmoidoscopy. From 1997 through 2018, 1913 women were diagnosed with an adenoma. Compared to nonaspirin users, regular users had 14% (OR = 0.86, 95% CI: 0.78-0.95) lower odds of adenoma. The odds of adenoma decreased with increasing duration of aspirin use (≥10 years: OR = 0.80, 95% CI: 0.66-0.96). Initiating aspirin at a younger age was associated with a reduced adenoma occurrence (age < 40 years at initiation: OR = 0.69, 95% CI: 0.55-0.86). Regular aspirin use was associated with a decreased odds of colorectal adenoma in our study of Black women. These findings support evidence demonstrating a chemopreventive impact of aspirin on colorectal neoplasia and suggest that aspirin may be a useful prevention strategy among US Black women.


Asunto(s)
Adenoma , Antiinflamatorios no Esteroideos , Aspirina , Negro o Afroamericano , Neoplasias Colorrectales , Adulto , Femenino , Humanos , Acetaminofén , Adenoma/epidemiología , Adenoma/etnología , Adenoma/prevención & control , Antiinflamatorios no Esteroideos/uso terapéutico , Aspirina/uso terapéutico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/prevención & control , Neoplasias Colorrectales/tratamiento farmacológico , Estudios Prospectivos , Estados Unidos/epidemiología
3.
Mayo Clin Proc ; 96(5): 1203-1217, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33840520

RESUMEN

OBJECTIVE: To estimate the cost-effectiveness of multitarget stool DNA testing (MT-sDNA) compared with colonoscopy and fecal immunochemical testing (FIT) for Alaska Native adults. PATIENTS AND METHODS: A Markov model was used to evaluate the 3 screening test effects over 40 years. Outcomes included colorectal cancer (CRC) incidence and mortality, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). The study incorporated updated evidence on screening test performance and adherence and was conducted from December 15, 2016, through November 6, 2019. RESULTS: With perfect adherence, CRC incidence was reduced by 52% (95% CI, 46% to 56%) using colonoscopy, 61% (95% CI, 57% to 64%) using annual FIT, and 66% (95% CI, 63% to 68%) using MT-sDNA. Compared with no screening, perfect adherence screening extends life by 0.15, 0.17, and 0.19 QALYs per person with colonoscopy, FIT, and MT-sDNA, respectively. Colonoscopy is the most expensive strategy: approximately $110 million more than MT-sDNA and $127 million more than FIT. With imperfect adherence (best case), MT-sDNA resulted in 0.12 QALYs per person vs 0.05 and 0.06 QALYs per person by FIT and colonoscopy, respectively. Probabilistic sensitivity analyses supported the base-case analysis. Under varied adherence scenarios, MT-sDNA either dominates or is cost-effective (ICERs, $1740-$75,868 per QALY saved) compared with FIT and colonoscopy. CONCLUSION: Each strategy reduced costs and increased QALYs compared with no screening. Screening by MT-sDNA results in the largest QALY savings. In Markov model analysis, screening by MT-sDNA in the Alaska Native population was cost-effective compared with screening by colonoscopy and FIT for a wide range of adherence scenarios.


Asunto(s)
Adenoma/diagnóstico , Colonoscopía/economía , Neoplasias Colorrectales/diagnóstico , Análisis Costo-Beneficio , ADN/análisis , Detección Precoz del Cáncer/métodos , Sangre Oculta , Adenoma/economía , Adenoma/etnología , Adenoma/metabolismo , Adulto , Anciano , Alaska/epidemiología , Biomarcadores/análisis , Biomarcadores/metabolismo , Neoplasias Colorrectales/economía , Neoplasias Colorrectales/etnología , Neoplasias Colorrectales/metabolismo , Simulación por Computador , Detección Precoz del Cáncer/economía , Heces/química , Femenino , Humanos , Incidencia , Masculino , Cadenas de Markov , Persona de Mediana Edad , Modelos Económicos , Cooperación del Paciente/estadística & datos numéricos , Años de Vida Ajustados por Calidad de Vida
4.
Fam Cancer ; 20(2): 111-116, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-32743790

RESUMEN

Germline variants in the APC and MUTYH genes contribute to colorectal cancer (CRC) and adenoma risk, though may occur with varying frequencies in individuals of different ancestries. The aim of this study was to evaluate the prevalence of APC, monoallelic MUTYH and biallelic MUTYH germline variants in Ashkenazi Jewish (AJ) and Other Ancestry (OA) individuals with colorectal adenomas. We studied 7225 individuals with colorectal adenomas who had germline APC and MUTYH testing at a commercial laboratory. Cross-sectional medical history data were extracted from provider-completed test requisition forms. We performed bivariate analysis to compare the frequency of APC and MUTYH variants between AJ and OA, and examined APC p.I1307K and monoallelic MUTYH carrier phenotypes using logistic regression. Pathogenic APC variants occurred in 38/285 AJ (13%) and 1342/6940 OA (19%; P = 0.09); biallelic MUTYH variants in 2/285 (1%) AJ and 399/6940 (6%) OA (P < 0.0001); APC p.I1307K in 35/285 (12%) AJ and 29/6940 (1%) OA (P < 0.0001); and monoallelic MUTYH in 2/285 (1%) AJ and 133/6940 (2%) OA (P = 0.06). Monoallelic MUTYH variants were significantly associated with having a personal history of CRC, regardless of ancestry (OR 1.78; 95% CI 1.21-2.49; P < 0.01), but no significant association was found between APC p.I1307K variants and personal history of CRC (OR 1.38; 95% CI 0.79-2.44; P = 0.26). Ashkenazim with colorectal adenomas rarely have monoallelic or biallelic MUTYH variants, suggesting different genetic etiologies for polyposis in AJ compared to OA individuals. AJ ancestry assessment may be important in clinical evaluation for polyposis.


Asunto(s)
Adenoma/genética , Neoplasias Colorrectales/genética , ADN Glicosilasas/genética , Genes APC , Mutación de Línea Germinal/genética , Judíos/genética , Adenoma/etnología , Estudios de Cohortes , Neoplasias Colorrectales/etnología , Femenino , Frecuencia de los Genes , Pruebas Genéticas , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fenotipo
5.
Cancer Epidemiol Biomarkers Prev ; 30(1): 3-12, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33144285

RESUMEN

Racial disparities in colorectal cancer incidence are widely documented. There are two potential mechanisms for these disparities: differences in access to screening, including screening follow-up, and differences in underlying risk of colorectal cancer. We reviewed the literature for evidence of these two mechanisms. We show that higher colorectal cancer incidence in blacks relative to whites emerged only after the dissemination of screening and describe evidence of racial disparities in screening rates. In contrast to the strong evidence for differences in colorectal cancer screening utilization, there is limited evidence for racial differences in adenoma prevalence. In general, black and white patients who are screened have similar adenoma prevalence, though there is some evidence that advanced adenomas and adenomas in the proximal colon are somewhat more likely in black than white patients. We conclude that higher rates of colorectal cancer incidence among black patients are primarily driven by lower rates of colorectal cancer screening. Our findings highlight the need to increase black patients' access to quality screening to reduce colorectal cancer incidence and mortality.


Asunto(s)
Adenoma/etnología , Neoplasias Colorrectales/etnología , Disparidades en el Estado de Salud , Tamizaje Masivo/estadística & datos numéricos , Adenoma/prevención & control , Negro o Afroamericano/estadística & datos numéricos , Neoplasias Colorrectales/prevención & control , Humanos , Incidencia , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Factores de Riesgo , Estados Unidos/epidemiología , Población Blanca/estadística & datos numéricos
6.
Signal Transduct Target Ther ; 5(1): 121, 2020 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-32641705

Asunto(s)
Betacoronavirus/genética , Colon/virología , Infecciones por Coronavirus/genética , Interacciones Huésped-Patógeno/genética , Neumonía Viral/genética , Receptores Virales/genética , Transcriptoma , Adenoma/etnología , Adenoma/genética , Adenoma/patología , Enzima Convertidora de Angiotensina 2 , Pueblo Asiatico , Basigina/genética , Basigina/metabolismo , Betacoronavirus/metabolismo , Betacoronavirus/patogenicidad , COVID-19 , Catepsina B/genética , Catepsina B/metabolismo , Catepsina L/genética , Catepsina L/metabolismo , Colon/metabolismo , Colon/patología , Neoplasias Colorrectales/etnología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Infecciones por Coronavirus/etnología , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Células Epiteliales/metabolismo , Células Epiteliales/patología , Células Epiteliales/virología , Furina/genética , Furina/metabolismo , Humanos , Interleucina-6/sangre , Interleucina-6/genética , Pandemias , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/etnología , Neumonía Viral/patología , Neumonía Viral/virología , Receptores Virales/metabolismo , SARS-CoV-2 , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Índice de Severidad de la Enfermedad , Análisis de la Célula Individual , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genética , Internalización del Virus
7.
Cancer Causes Control ; 31(4): 291-302, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32124186

RESUMEN

PURPOSE: Evidence for the association of anthropometrics with colorectal neoplasms is limited for African Americans. METHODS: We examined anthropometric measures with both colorectal adenoma and colorectal cancer (CRC) risk in the ongoing Black Women's Health Study. In a nested case-control analysis, 954 cases of colorectal adenoma were compared with 3,816 polyp-free controls, matched on age and follow-up time. For the CRC analyses, 413 incident CRC cases were identified over a 16-year follow-up (802,783 person-years). Adenoma cases and CRC were verified by medical record review. We used multivariable conditional logistic regression analyses (for adenoma) and Cox proportional hazards analyses (for CRC) that included anthropometric exposures and selected confounders. RESULTS: Overall body mass index (BMI) and other anthropometric factors were not associated with colorectal adenoma or cancer risk in Black women. However, increased risk of adenoma (but not CRC) was observed among especially related to adenomas in the proximal colon. Among women ≥ 50 years of age, risk of proximal adenoma increased 14% (95% CI 1.00, 1.31), 35% (95% CI 1.12, 1.63), and 25% (0.93, 1.68) with each standard deviation increase in BMI, waist circumference, and waist-to-hip ratio, respectively. None of the anthropometric factors were associated with young onset CRC or adenoma risk. CONCLUSION: Our results suggest that obesity might be an initiator for colon adenomas but not a promoter for colorectal cancer among Black women.


Asunto(s)
Adenoma/epidemiología , Negro o Afroamericano/estadística & datos numéricos , Neoplasias Colorrectales/epidemiología , Obesidad/epidemiología , Adenoma/etnología , Adenoma/etiología , Adulto , Antropometría/métodos , Índice de Masa Corporal , Estudios de Casos y Controles , Estudios de Cohortes , Neoplasias Colorrectales/etnología , Neoplasias Colorrectales/etiología , Femenino , Humanos , Incidencia , Modelos Logísticos , Masculino , Obesidad/complicaciones , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Salud de la Mujer
8.
Dig Dis Sci ; 65(8): 2412-2418, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-31745688

RESUMEN

BACKGROUND/AIMS: The black population in the USA is a heterogeneous group composed of smaller subgroups from different origins. The definition of black in many colorectal cancer (CRC) risk studies is vague, and differences in CRC risk comparing black subpopulations have not been evaluated. The aim of the study is to compare advanced colorectal neoplasia (ACN) between two subgroups of black populations: African-American (AA) and Afro-Caribbean (AC). A secondary aim was to determine whether there are differences in prevalence of adenomas. METHODS: This was a retrospective study of 3797 AA and AC patients undergoing first time screening colonoscopy in two different institutions in the USA. RESULTS: Overall adenoma prevalence was 29.3% for the entire population with 29.5% in AAs and 29.0% in AC with no statistically significant difference between the study groups (AOR: 1.02; 95% CI 0.88-1.18, P = 0.751). However, ACN was significantly higher in the AA group (11.8%) compared to AC (9.0%) (AOR: 1.30, 95% CI 1.02-1.66, P = 0.034). It was observed that AAs had ACN at a higher BMI than AC. After adjusting for BMI/ethnicity interactions, the difference in ACN between both groups became more significant (AOR: 1.93, 95% CI 1.16-3.23, P = 0.012). CONCLUSIONS: AAs have a higher risk of ACN than AC. Current recommendations to start screening in average-risk AAs at an earlier age may not apply to other black subgroups.


Asunto(s)
Adenoma/etnología , Negro o Afroamericano/estadística & datos numéricos , Neoplasias del Colon/etnología , Anciano , Región del Caribe/etnología , Femenino , Florida/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Ohio/epidemiología , Prevalencia , Estudios Retrospectivos
9.
Clin Lab ; 64(9): 1573-1579, 2018 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-30273999

RESUMEN

BACKGROUND: This study aimed to investigate the detection of methylated Septin 9 (mSEPT9) in Korean patients with colorectal cancer (CRC) and compare the results with those of previous studies. METHODS: A total of 127 plasma samples (111 patients with untreated CRC, 5 patients with adenomas, and 11 CRC patients treated with concurrent chemoradiotherapy before surgery) were collected. mSEPT9 was measured qualitatively with the Abbott RealTime ms9 Colorectal Cancer Assay. RESULTS: mSEPT9 was detected in 44 of 111 (39.6%) cases of untreated CRC but was not detected in the adenoma cases. The difference in the sensitivity of mSEPT9 among patients with adenomas and those with each stage of untreated CRC was statistically significant (Dukes' staging, p = 0.002 and TNM staging, p = 0.008). The sensitivity of mSEPT9 for each of the stages (I - IV) of untreated CRC patients were 20.7%, 54.1%, 36.6%, and 75.0%, respectively. The positive mSEPT9 results in untreated CRC patients reverted to negative in 19 of 21 patients (90.5%) after treatment. CONCLUSIONS: Compared to previous studies, the overall sensitivity of mSEPT9 was lower, but similar patterns were found in the sensitivities for each stage. Additionally, mSEPT9 appeared to have potential as a monitoring tool for CRC.


Asunto(s)
Adenoma/genética , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , Metilación de ADN , Septinas/genética , Adenoma/etnología , Adenoma/patología , Adenoma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico/genética , Neoplasias Colorrectales/etnología , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Fenotipo , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reacción en Cadena en Tiempo Real de la Polimerasa , República de Corea/epidemiología
10.
BMC Med Genet ; 19(1): 182, 2018 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-30290787

RESUMEN

BACKGROUND: It has been reported that the single nucleotide polymorphism (SNP) rs2854744 at the - 202 locus of insulin-like growth factor binding protein-3 (IGFBP3) is associated with serum levels and a number of malignancies. However, the effect of IGFBP3 gene polymorphism on acromegaly is less clear. Therefore, in the current study, we aimed to investigate whether the -202A/C polymorphism of IGFBP3 constitutes a risk factor for acromegaly. METHODS: The study included 102 acromegalic patients and 143 control subjects in Beijing Tiantan Hospital. The genotyping of IGFBP3 was carried out using the MassARRAY method. Serum IGFBP3 concentrations were also determined. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the associations of genetic polymorphisms with the development of acromegaly and its different subtypes. RESULTS: The study revealed that the C allele of rs2854744 was associated with a reduced risk of acromegaly (OR 0.594, 95% CI 0.388-0.909), as well as with the female (OR 0.385, 95% CI 0.206-0.72), macroadenoma (OR 0.557, 95% CI 0.347-0.893) and monotherapy (OR 0.512, 95% CI 0.316-0.828) subgroups under the additive model. A higher serum IGFBP3 level was observed in patients with the AA genotype, but this difference was not significant (P = 0.331). CONCLUSION: This study is one of the first to show that the IGFBP3 polymorphism may have an influence on serum levels and that the C allele of rs2854744 is associated with a reduced risk of acromegaly. This correlation was more prominent in females, those with large tumours and those treated with monotherapy in a Chinese population. Genetic polymorphism of IGFBP3 may be involved in the development of acromegaly.


Asunto(s)
Acromegalia/genética , Adenoma/genética , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Neoplasias Hipofisarias/genética , Polimorfismo de Nucleótido Simple , Regiones no Traducidas 5' , Acromegalia/sangre , Acromegalia/complicaciones , Acromegalia/etnología , Adenoma/sangre , Adenoma/complicaciones , Adenoma/etnología , Adulto , Alelos , Pueblo Asiatico , Estudios de Casos y Controles , Femenino , Expresión Génica , Frecuencia de los Genes , Genotipo , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Neoplasias Hipofisarias/sangre , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/etnología , Factores de Riesgo , Factores Sexuales
11.
Cancer ; 124(19): 3876-3880, 2018 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-30193399

RESUMEN

BACKGROUND: Multitarget stool DNA (mt-sDNA) is an approved method for colon cancer screening that is especially relevant for patients who cannot undergo colonoscopy. Although the test performance has been evaluated in a large clinical trial, it was limited to a predominantly white population. Given differences in the epidemiology and biology of colon cancer in African American individuals, the authors sought to compare the performance of mt-sDNA between racial groups. METHODS: The authors prospectively identified patients aged ≥40 years who were referred for colonoscopy at an academic medical center and 2 satellite facilities. Prior to the colonoscopy, the authors collected stool for mt-sDNA and fecal immunochemical testing (FIT). They compared the sensitivity, specificity, and receiver operating characteristic curve between African American and white patients for the detection of advanced lesions or any adenoma. RESULTS: A total of 760 patients were included, 34.9% of whom were African American. The prevalence of any adenoma (38.9% for African American patients and 33.9% for white patients) and that for advanced lesions (6.8% and 6.7%, respectively) were similar between groups. The overall sensitivities of mt-sDNA for the detection of advanced lesions and any adenoma were 43% and 19%, respectively, and the specificities were 91% and 93%, respectively. In general, mt-sDNA was more sensitive and less specific than FIT. When stratified by race, the sensitivity, specificity, and receiver operating characteristic curve area were similar between African American and white patients for both mt-sDNA and FIT. CONCLUSIONS: Test performance characteristics of mt-sDNA were comparable in African American and white patients. Given the lower uptake of colonoscopy in African American individuals, mt-sDNA may offer a promising screening alternative in this patient population.


Asunto(s)
Adenoma/diagnóstico , Negro o Afroamericano , Pólipos del Colon/diagnóstico , Neoplasias Colorrectales/diagnóstico , ADN de Neoplasias/análisis , Detección Precoz del Cáncer/métodos , Sangre Oculta , Adenoma/etnología , Adenoma/genética , Adulto , Negro o Afroamericano/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Pólipos del Colon/etnología , Pólipos del Colon/genética , Colonoscopía/estadística & datos numéricos , Neoplasias Colorrectales/etnología , Neoplasias Colorrectales/genética , Detección Precoz del Cáncer/estadística & datos numéricos , Femenino , Humanos , Masculino , Tamizaje Masivo/métodos , Tamizaje Masivo/estadística & datos numéricos , Persona de Mediana Edad , Sensibilidad y Especificidad
12.
Clin Lab ; 64(7): 1163-1170, 2018 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-30146828

RESUMEN

BACKGROUND: H. pylori infection has been reported as a risk factor for colorectal adenoma (CRA); however, the clinical results were controversial. Therefore, we performed a meta-analysis to evaluate the association of H. pylori infection and CRA risk. METHODS: A comprehensive literature search for relevant studies published up to November 2017 was performed using Medline and Embase, and the statistical analysis was conducted using Stata software. RESULTS: A total of twenty-five studies including 8,675 cases and 15,275 controls were included in the analysis. The pooled analysis showed that H. pylori infection was associated with an increased risk of CRA (OR = 1.86, 95% CI = 1.55 - 2.23). Subgroup analyses according to the ethnicity, study type, and H. pylori detection method were further conducted. The results showed that H. pylori infection was associated with an increased risk of CRA both in Caucasian (OR = 2.23, 95% CI = 1.36 - 3.66) and Asian population (OR = 1.58, 95% CI = 1.36 - 1.82). Both the case-control studies and cross sectional studies suggested the H. pylori infection could promote the risk of CRA (case control: OR was 2.00, 95% CI = 1.22 - 3.28; cross-sectional: OR was 1.68, 95% CI = 1.43 - 1.99). For H. pylori infection detection methods, there is significant association between H. pylori infection and CRA risk using the serum IgG method and RUT, but not with the UBT and IHC method. CONCLUSIONS: This analysis suggests that H. pylori infection may be a risk factor for CRA.


Asunto(s)
Adenoma/diagnóstico , Neoplasias Colorrectales/diagnóstico , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/aislamiento & purificación , Adenoma/inducido químicamente , Adenoma/etnología , Pueblo Asiatico/estadística & datos numéricos , Estudios de Casos y Controles , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/etnología , Estudios Transversales , Infecciones por Helicobacter/etnología , Infecciones por Helicobacter/virología , Helicobacter pylori/fisiología , Humanos , Factores de Riesgo , Población Blanca/estadística & datos numéricos
13.
Dis Colon Rectum ; 61(9): 1073-1079, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30086056

RESUMEN

BACKGROUND: Germline mutations in the DNA polymerase genes POLD1 and POLE confer high risk for multiple colorectal adenomas and colorectal cancer. However, prevalence and the clinical phenotype of mutation carriers are still not fully characterized. OBJECTIVE: The purpose of this study was to assess the prevalence of germline mutations and to describe the genotype-phenotype correlation in POLD1 and POLE genes in Jewish subjects with multiple colorectal adenomas and/or early-onset mismatch repair proficient colorectal cancers. DESIGN: This study is a comparison of genetic and clinical data from affected and control groups. SETTINGS: The study was conducted at a high-volume tertiary referral center. PATIENTS: The study cohort included 132 subjects: 68 with multiple colorectal adenomas and 64 with early-onset mismatch repair proficient colorectal cancers. The control group included 5685 individuals having no colorectal cancer or colorectal adenomas. MAIN OUTCOME MEASURES: Study and control subjects were tested for POLD1 and POLE mutations and a clinical correlation was assessed. RESULTS: Eleven of the 132 study subjects (8.3%) carried either a POLD1 or a POLE mutation: 7 of 68 (10.3%) subjects with multiple colorectal adenomas and 4 of 64 (6.2%) subjects with early-onset mismatch repair proficient colorectal cancer. Three mutations were detected, showing statistical significance in frequency between study and control groups (p < 0.001). Eight of the 11 mutation carriers were Ashkenazi Jews carrying the same POLD1 mutation (V759I), implicating it as a possible low-to-moderate risk founder mutation. Phenotype of mutation carriers was notable for age under 50 at diagnosis, a propensity toward left-sided colorectal cancer, and extracolonic tumors (64%, 100%, and 27% of cases). LIMITATIONS: The study cohort was limited by its relatively small size. CONCLUSIONS: Germline mutations in POLD1 and POLE were found to be relatively frequent in our Jewish cohorts. Further studies are needed to clarify the importance of POLD1 and POLE mutations and to define the most suitable surveillance program for Jewish and other POLD1 and POLE mutation carriers. See Video Abstract at http://links.lww.com/DCR/A658.


Asunto(s)
Adenoma/genética , Neoplasias Colorrectales/genética , ADN Polimerasa III/genética , ADN Polimerasa II/genética , Proteínas de Unión a Poli-ADP-Ribosa/genética , Adenoma/etnología , Adulto , Anciano , Neoplasias Colorrectales/etnología , Reparación de la Incompatibilidad de ADN , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Judíos , Masculino , Persona de Mediana Edad , Mutación , Prevalencia , Sistema de Registros
14.
Eur J Epidemiol ; 33(1): 15-26, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29288474

RESUMEN

The objective of this meta-analysis is to evaluate the odds of colorectal adenoma (CRA) in colorectal cancer screening participants with different body mass index (BMI) levels, and examine if this association was different according to gender and ethnicity. The EMBASE and MEDLINE were searched to enroll high quality observational studies that examined the association between investigator-measured BMI and colonoscopy-diagnosed CRA. Data were independently extracted by two reviewers. A random-effects meta-analysis was conducted to estimate the summary odds ratio (SOR) for the association between BMI and CRA. The Cochran's Q statistic and I2 analyses were used to assess the heterogeneity. A total of 17 studies (168,201 subjects) were included. When compared with subjects having BMI < 25, individuals with BMI 25-30 had significantly higher risk of CRA (SOR 1.44, 95% CI 1.30-1.61; I2 = 43.0%). Subjects with BMI ≥ 30 had similarly higher risk of CRA (SOR 1.42, 95% CI 1.24-1.63; I2 = 18.5%). The heterogeneity was mild to moderate among studies. The associations were significantly higher than estimates by previous meta-analyses. There was no publication bias detected (Egger's regression test, p = 0.584). Subgroup analysis showed that the magnitude of association was significantly higher in female than male subjects (SOR 1.43, 95% CI 1.30-1.58 vs. SOR 1.16, 95% CI 1.07-1.24; different among different ethnic groups (SOR 1.72, 1.44 and 0.88 in White, Asians and Africans, respectively) being insignificant in Africans; and no difference exists among different study designs. In summary, the risk conferred by BMI for CRA was significantly higher than that reported previously. These findings bear implications in CRA risk estimation.


Asunto(s)
Adenoma/etiología , Neoplasias Colorrectales/etiología , Obesidad/complicaciones , Adenoma/etnología , Adenoma/patología , Índice de Masa Corporal , Neoplasias Colorrectales/etnología , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/prevención & control , Femenino , Humanos , Masculino , Obesidad/diagnóstico , Obesidad/etnología , Factores de Riesgo
15.
Dig Dis Sci ; 62(6): 1637-1646, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-27913995

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is the second leading malignancy diagnosed among US Latinos. Latinos in the USA represent a heterogeneous amalgam of subgroups varying in genetic background, culture, and socioeconomic status. Little is known about the frequency of CRC precursor lesions found at screening colonoscopy among Latino subgroups. AIM: The aim was to determine the prevalence and distribution of histologically confirmed adenomas found at screening colonoscopy among average-risk, asymptomatic US Latinos according to their subgroup and socio-demographic background. METHODS: Cross-sectional analysis of pathological findings resulting from screening colonoscopy among average-risk, asymptomatic US Latinos aged ≥50 in two prospective randomized controlled trials at an academic medical center. RESULTS: Among the 561 Latinos who completed screening colonoscopy, the two largest subgroups were Puerto Ricans and Dominicans. The findings among both subgroups were: adenomas 30.6%, proximal adenomas 23.5%, advanced adenomas 12.0%, and proximal advanced adenomas 8.9%. These rates are at least as high as those found at screening colonoscopy among US whites. While Puerto Ricans were more likely than Dominicans to be born in the USA, speak English, be acculturated, have a smoking history, and be obese, there were no significant differences in adenoma rates between these subgroups. CONCLUSIONS: The prevalence of adenomas, advanced adenomas, and proximal neoplasia was high among both subgroups. These findings have implications for CRC screening and surveillance among the increasingly growing Latino population in the USA.


Asunto(s)
Adenoma/etnología , Adenoma/patología , Neoplasias Colorrectales/etnología , Neoplasias Colorrectales/patología , Hispánicos o Latinos/estadística & datos numéricos , Aculturación , Adenoma/diagnóstico por imagen , Factores de Edad , Anciano , Colonoscopía , Neoplasias Colorrectales/diagnóstico por imagen , Estudios Transversales , República Dominicana/etnología , Detección Precoz del Cáncer , Emigración e Inmigración , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Puerto Rico/etnología , Fumar/etnología , Factores Socioeconómicos , Estados Unidos/epidemiología
16.
Oncotarget ; 7(47): 77651-77663, 2016 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-27769063

RESUMEN

BACKGROUND: Recent genome-wide association studies (GWAS) identified eighteen single-nucleotide polymorphisms (SNPs) to be significantly associated with the risk of colorectal cancer (CRC). However, overall results of the following replications are inconsistent and little is known about whether these associations also exit in colorectal adenomas (CRA). METHODS: The SNP genotyping was performed using a Sequenom MassARRAY to investigate the association of these eighteen SNPs with colorectal neoplasm in a case-control study consisted of 1049 colorectal cancers, 283 adenomas, and 1030 controls. RESULTS: Two of these SNPs, rs10505477 and rs719725, showed evidence of an association in both CRC and CRA in our study population. Besides, seven SNPs (rs10808555, rs7014346, rs7837328, rs704017, rs11196172, rs4779584, and rs7229639) were significantly associated with CRC, and another one SNP rs11903757 was over-represented in CRA compared with controls. The strongest association was provided by rs11196172 (OR = 2.02, 95% CI = 1.66 - 2.46, P < 0.0001) and rs11903757 (OR = 1.96, 95% CI = 1.28 - 3.00, P = 0.0026). CONCLUSION: These results suggest that some previously reported SNP associations also have impact on CRC and CRA predispositions in the Han Chinese population. A part of genetic risk to CRC is possibly mediated by susceptibility to adenomas.


Asunto(s)
Adenoma/genética , Pueblo Asiatico/genética , Neoplasias Colorrectales/genética , Estudio de Asociación del Genoma Completo/métodos , Polimorfismo de Nucleótido Simple , Adenoma/etnología , Anciano , Pueblo Asiatico/etnología , Estudios de Casos y Controles , China/etnología , Neoplasias Colorrectales/etnología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad
17.
Endocr J ; 63(11): 953-963, 2016 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-27498687

RESUMEN

Most of acromegaly is caused by a sporadic somatotropinoma and a couple of novel gene mutations responsible for somatotropinoma have recently been reported. To determine the cause of sporadic somatotropinoma in Japanese patients, we analyzed 61 consecutive Japanese patients with somatotropinoma without apparent family history. Comprehensive genetic analysis revealed that 31 patients harbored guanine nucleotide-binding protein, alpha stimulating (GNAS) mutations (50.8%) and three patients harbored aryl hydrocarbon receptor interacting protein (AIP) mutations (4.9%). No patients had G protein-coupled receptor 101 (GPR101) mutations. The patients in this cohort study were categorized into three groups of AIP, GNAS, and others and compared the clinical characteristics. The AIP group exhibited significantly younger age at diagnosis, larger tumor, and higher nadir GH during oral glucose tolerance test. In all patients with AIP mutation, macro- and invasive tumor was detected and repetitive surgery or postoperative medical therapy was needed. One case showed a refractory response to postoperative somatostatin analogue (SSA) but after the addition of cabergoline as combined therapy, serum IGF-I levels were controlled. The other case showed a modest response to SSA and the switching to cabergoline monotherapy was also effective. These data suggest that although resistance to SSA has been reported in patients with AIP mutations, the response to dopamine agonist (DA) may be retained. In conclusion, the cause of sporadic somatotropinoma in Japanese patients was comparable with the previous reports in Caucasians, patients with AIP mutations showed unique clinical characteristics, and DA may be a therapeutic option for patients with AIP mutations.


Asunto(s)
Adenoma/genética , Adenoma/patología , Adenoma Hipofisario Secretor de Hormona del Crecimiento/genética , Adenoma Hipofisario Secretor de Hormona del Crecimiento/patología , Acromegalia/etnología , Acromegalia/genética , Acromegalia/patología , Adenoma/etnología , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Cromograninas/genética , Análisis Mutacional de ADN , Femenino , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Predisposición Genética a la Enfermedad , Adenoma Hipofisario Secretor de Hormona del Crecimiento/etnología , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Japón/etnología , Masculino , Persona de Mediana Edad , Mutación , Adulto Joven
18.
Cancer Prev Res (Phila) ; 9(11): 844-854, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27549371

RESUMEN

Alterations in high order chromatin, with concomitant modulation in gene expression, are one of the earliest events in the development of colorectal cancer. Cohesins are a family of proteins that modulate high-order chromatin, although the role in colorectal cancer remains incompletely understood. We, therefore, assessed the role of cohesin SA1 in colorectal cancer biology and as a biomarker focusing in particular on the increased incidence/mortality of colorectal cancer among African-Americans. Immunohistochemistry on tissue arrays revealed dramatically decreased SA1 expression in both adenomas (62%; P = 0.001) and adenocarcinomas (75%; P = 0.0001). RT-PCR performed in endoscopically normal rectal biopsies (n = 78) revealed a profound decrease in SA1 expression in adenoma-harboring patients (field carcinogenesis) compared with those who were neoplasia-free (47%; P = 0.03). From a racial perspective, colorectal cancer tissues from Caucasians had 56% higher SA1 expression than in African-Americans. This was mirrored in field carcinogenesis where healthy Caucasians expressed more SA1 at baseline compared with matched African-American subjects (73%; P = 0.003). However, as a biomarker for colorectal cancer risk, the diagnostic performance as assessed by area under ROC curve was greater in African-Americans (AUROC = 0.724) than in Caucasians (AUROC = 0.585). From a biologic perspective, SA1 modulation of high-order chromatin was demonstrated with both biophotonic (nanocytology) and chromatin accessibility [micrococcal nuclease (MNase)] assays in SA1-knockdown HT29 colorectal cancer cells. The functional consequences were underscored by increased proliferation (WST-1; P = 0.0002, colony formation; P = 0.001) in the SA1-knockdown HT29 cells. These results provide the first evidence indicating a tumor suppressor role of SA1 in early colon carcinogenesis and as a risk stratification biomarker giving potential insights into biologic basis of racial disparities in colorectal cancer. Cancer Prev Res; 9(11); 844-54. ©2016 AACR.


Asunto(s)
Adenocarcinoma/etnología , Adenoma/etnología , Biomarcadores de Tumor/análisis , Neoplasias del Colon/etnología , Proteínas Nucleares/metabolismo , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Adenoma/diagnóstico , Adenoma/metabolismo , Negro o Afroamericano , Carcinogénesis , Cromatina , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/metabolismo , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Población Blanca
19.
Ann Surg Oncol ; 23(Suppl 5): 946-953, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27401449

RESUMEN

BACKGROUND: Sichuan is a province in the west of China with a population of 81.4 million. This is the first statistical report of central nervous system (CNS) tumors surgically treated and histologically diagnosed in a large Chinese population. METHODS: All the patient data were obtained from 86 medical facilities, which covered the Sichuan province population. Data from patients who underwent surgery between 2008 and 2013 and corresponding histology samples were re-reviewed in the major pathology centers. All the CNS tumors were categorized according to International Classification of Diseases (ICD)-10 and ICD-O-3 classifications and reviewed manually. The tumor distribution was analyzed and stratified by gender, age, race, and tumor sites. Tumors in some ethnic minorities, such as the Tibetan people, also were analyzed. RESULTS: The final analytic dataset included 35,496 records. The top four histologic tumors were meningioma (28.51 %), pituitary adenoma (15.00 %), nerve sheath (13.77 %), and glioblastoma (11.82 %). There was a dramatically high incidence of malignant tumor in males. The median age at diagnosis ranged from 13 years (pineal region tumors) to 56 years (metastatic brain tumors). Most of the tumors in the insular lobe or cerebellum were low grade, whereas those in the thalamus or basal ganglia were likely to be high grade. The incidence of malignant tumors or high-grade gliomas in the Tibetans was significantly lower than in the Chinese Han population. CONCLUSION: This report is a preliminary statistical analysis of brain and spinal tumors in a large Chinese population and may serve as a useful resource for clinicians, researchers, and patients' families.


Asunto(s)
Adenoma/epidemiología , Neoplasias Encefálicas/epidemiología , Encéfalo/patología , Glioblastoma/epidemiología , Meningioma/epidemiología , Neoplasias de la Vaina del Nervio/epidemiología , Neoplasias de la Médula Espinal/epidemiología , Adenoma/etnología , Adenoma/patología , Adolescente , Adulto , Factores de Edad , Neoplasias Encefálicas/etnología , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/secundario , Niño , Preescolar , China/epidemiología , Femenino , Glioblastoma/etnología , Glioblastoma/patología , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Meningioma/etnología , Meningioma/patología , Persona de Mediana Edad , Neoplasias de la Vaina del Nervio/etnología , Neoplasias de la Vaina del Nervio/patología , Neoplasias Hipofisarias/epidemiología , Neoplasias Hipofisarias/patología , Factores Sexuales , Neoplasias de la Médula Espinal/etnología , Neoplasias de la Médula Espinal/patología , Neoplasias de la Médula Espinal/secundario , Tibet/etnología , Adulto Joven
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