Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Breast Cancer Res ; 26(1): 16, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263039

RESUMO

BACKGROUND: Contralateral breast cancer (CBC) is the most common second primary cancer diagnosed in breast cancer survivors, yet the understanding of the genetic susceptibility of CBC, particularly with respect to common variants, remains incomplete. This study aimed to investigate the genetic basis of CBC to better understand this malignancy. FINDINGS: We performed a genome-wide association analysis in the Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study of women with first breast cancer diagnosed at age < 55 years including 1161 with CBC who served as cases and 1668 with unilateral breast cancer (UBC) who served as controls. We observed two loci (rs59657211, 9q32, SLC31A2/FAM225A and rs3815096, 6p22.1, TRIM31) with suggestive genome-wide significant associations (P < 1 × 10-6). We also found an increased risk of CBC associated with a breast cancer-specific polygenic risk score (PRS) comprised of 239 known breast cancer susceptibility single nucleotide polymorphisms (SNPs) (rate ratio per 1-SD change: 1.25; 95% confidence interval 1.14-1.36, P < 0.0001). The protective effect of chemotherapy on CBC risk was statistically significant only among patients with an elevated PRS (Pheterogeneity = 0.04). The AUC that included the PRS and known breast cancer risk factors was significantly elevated. CONCLUSIONS: The present GWAS identified two previously unreported loci with suggestive genome-wide significance. We also confirm that an elevated risk of CBC is associated with a comprehensive breast cancer susceptibility PRS that is independent of known breast cancer risk factors. These findings advance our understanding of genetic risk factors involved in CBC etiology.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Humanos , Feminino , Pessoa de Meia-Idade , Estudo de Associação Genômica Ampla , Mama , Predisposição Genética para Doença , Estratificação de Risco Genético , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases
2.
Radiology ; 308(3): e230367, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37750771

RESUMO

Background Background parenchymal enhancement (BPE) at breast MRI has been associated with increased breast cancer risk in several independent studies. However, variability of subjective BPE assessments have precluded its use in clinical practice. Purpose To examine the association between fully objective measures of BPE at MRI and odds of breast cancer. Materials and Methods This prospective case-control study included patients who underwent a bilateral breast MRI examination and were receiving care at one of three centers in the United States from November 2010 to July 2017. Breast volume, fibroglandular tissue (FGT) volume, and BPE were quantified using fully automated software. Fat volume was defined as breast volume minus FGT volume. BPE extent was defined as the proportion of FGT voxels with enhancement of 20% or more. Spearman rank correlation between quantitative BPE extent and Breast Imaging Reporting and Data System (BI-RADS) BPE categories assigned by an experienced board-certified breast radiologist was estimated. With use of multivariable logistic regression, breast cancer case-control status was regressed on tertiles (low, moderate, and high) of BPE, FGT volume, and fat volume, with adjustment for covariates. Results In total, 536 case participants with breast cancer (median age, 48 years [IQR, 43-55 years]) and 940 cancer-free controls (median age, 46 years [IQR, 38-55 years]) were included. BPE extent was positively associated with BI-RADS BPE (rs = 0.54; P < .001). Compared with low BPE extent (range, 2.9%-34.2%), high BPE extent (range, 50.7%-97.3%) was associated with increased odds of breast cancer (odds ratio [OR], 1.74 [95% CI: 1.23, 2.46]; P for trend = .002) in a multivariable model also including FGT volume (OR, 1.39 [95% CI: 0.97, 1.98]) and fat volume (OR, 1.46 [95% CI: 1.04, 2.06]). The association of high BPE extent with increased odds of breast cancer was similar for premenopausal and postmenopausal women (ORs, 1.75 and 1.83, respectively; interaction P = .73). Conclusion Objectively measured BPE at breast MRI is associated with increased breast cancer odds for both premenopausal and postmenopausal women. Clinical trial registration no. NCT02301767 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Bokacheva in this issue.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/diagnóstico por imagem , Estudos de Casos e Controles , Imageamento por Ressonância Magnética , Mama/diagnóstico por imagem , Certificação
3.
Int J Cancer ; 151(8): 1304-1309, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-35315524

RESUMO

Mammographic dense area (MDA) is an established predictor of future breast cancer risk. Recent studies have found that risk prediction might be improved by redefining MDA in effect at higher-than-conventional intensity thresholds. We assessed whether such higher-intensity MDA measures gave stronger prediction of subsequent contralateral breast cancer (CBC) risk using the Women's Environment, Cancer, and Radiation Epidemiology (WECARE) Study, a population-based CBC case-control study of ≥1 year survivors of unilateral breast cancer diagnosed between 1990 and 2008. Three measures of MDA for the unaffected contralateral breast were made at the conventional intensity threshold ("Cumulus") and at two sequentially higher-intensity thresholds ("Altocumulus" and "Cirrocumulus") using the CUMULUS software and mammograms taken up to 3 years prior to the first breast cancer diagnosis. The measures were fitted separately and together in multivariable-adjusted logistic regression models of CBC (252 CBC cases and 271 unilateral breast cancer controls). The strongest association with CBC was MDA defined using the highest intensity threshold, Cirrocumulus (odds ratio per adjusted SD [OPERA] 1.40, 95% CI 1.13-1.73); and the weakest association was MDA defined at the conventional threshold, Cumulus (1.32, 95% CI 1.05-1.66). In a model fitting the three measures together, the association of CBC with Cirrocumulus was unchanged (1.40, 95% CI 0.97-2.05), and the lower brightness measures did not contribute to the CBC model fit. These results suggest that MDA defined at a high-intensity threshold is a better predictor of CBC risk and has the potential to improve CBC risk stratification beyond conventional MDA measures.


Assuntos
Neoplasias da Mama , Neoplasias Unilaterais da Mama , Densidade da Mama , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Fatores de Risco
4.
Int J Cancer ; 148(11): 2748-2758, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33544892

RESUMO

Breast cancer survivors have a high risk of a second primary contralateral breast cancer (CBC), but there are few studies of CBC risk in racial/ethnic minority populations. We examined whether the incidence and risk factors for CBC differed by race/ethnicity in the United States. Women with a first invasive Stage I-IIB breast cancer diagnosis at ages 20-74 years between 2000 and 2015 in the Surveillance, Epidemiology, and End Results Program (SEER) 18 registries were followed through 2016 for a diagnosis of invasive CBC ≥1 year after the first breast cancer diagnosis. We used cause-specific Cox proportional hazards models to test the association between race/ethnicity and CBC, adjusting for age, hormone receptor status, radiation therapy, chemotherapy and stage at first diagnosis, and evaluated the impact of contralateral prophylactic mastectomy, socioeconomic status, and insurance status on the association. After a median follow-up of 5.9 years, 9247 women (2.0%) were diagnosed with CBC. Relative to non-Hispanic (NH) White women, CBC risk was increased in NH Black women (hazard ratio = 1.44, 95% CI 1.35-1.54) and Hispanic women (1.11, 95% CI 1.02-1.20), with the largest differences among women diagnosed at younger ages. Adjustment for contralateral prophylactic mastectomy, socioeconomic status and health insurance did not explain the associations. Therefore, non-Hispanic Black and Hispanic women have an increased risk of CBC that is not explained by clinical or socioeconomic factors collected in SEER. Large studies of diverse breast cancer survivors with detailed data on treatment delivery and adherence are needed to inform interventions to reduce this disparity.


Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Neoplasias da Mama/epidemiologia , Hispânico ou Latino/estatística & dados numéricos , Segunda Neoplasia Primária/epidemiologia , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/cirurgia , Mastectomia Profilática , Modelos de Riscos Proporcionais , Medição de Risco , Programa de SEER , Estados Unidos/etnologia , Adulto Jovem
5.
Breast Cancer Res ; 22(1): 138, 2020 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-33287857

RESUMO

BACKGROUND: Background parenchymal enhancement (BPE) on breast magnetic resonance imaging (MRI) may be associated with breast cancer risk, but previous studies of the association are equivocal and limited by incomplete blinding of BPE assessment. In this study, we evaluated the association between BPE and breast cancer based on fully blinded assessments of BPE in the unaffected breast. METHODS: The Imaging and Epidemiology (IMAGINE) study is a multicenter breast cancer case-control study of women receiving diagnostic, screening, or follow-up breast MRI, recruited from three comprehensive cancer centers in the USA. Cases had a first diagnosis of unilateral breast cancer and controls had no history of or current breast cancer. A single board-certified breast radiologist with 12 years' experience, blinded to case-control status and clinical information, assessed the unaffected breast for BPE without view of the affected breast of cases (or the corresponding breast laterality of controls). The association between BPE and breast cancer was estimated by multivariable logistic regression separately for premenopausal and postmenopausal women. RESULTS: The analytic dataset included 835 cases and 963 controls. Adjusting for fibroglandular tissue (breast density), age, race/ethnicity, BMI, parity, family history of breast cancer, BRCA1/BRCA2 mutations, and other confounders, moderate/marked BPE (vs minimal/mild BPE) was associated with breast cancer among premenopausal women [odds ratio (OR) 1.49, 95% CI 1.05-2.11; p = 0.02]. Among postmenopausal women, mild/moderate/marked vs minimal BPE had a similar, but statistically non-significant, association with breast cancer (OR 1.45, 95% CI 0.92-2.27; p = 0.1). CONCLUSIONS: BPE is associated with breast cancer in premenopausal women, and possibly postmenopausal women, after adjustment for breast density and confounders. Our results suggest that BPE should be evaluated alongside breast density for inclusion in models predicting breast cancer risk.


Assuntos
Neoplasias da Mama/epidemiologia , Mama/diagnóstico por imagem , Imageamento por Ressonância Magnética/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Adulto , Idoso , Mama/patologia , Densidade da Mama , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Meios de Contraste/administração & dosagem , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética/métodos , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Adulto Jovem
6.
Clin Gastroenterol Hepatol ; 17(5): 968-975.e5, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29902644

RESUMO

BACKGROUND & AIMS: Hepatic fibrosis is a primary risk factor for cirrhosis and hepatocellular carcinoma, which affect a disproportionate number of Hispanics in the United States. We aimed to determine the prevalence of significant fibrosis, measured by point shear-wave elastography (pSWE), and determine characteristics of hepatic fibrosis and simple steatosis in a population-based study of Mexican American Hispanics in south Texas. METHODS: Liver stiffness was measured by pSWE, performed by 2 separate operators, for 406 participants in the Cameron County Hispanic Cohort from 2015 through 2017. Significant fibrosis (F2-F4) was defined as median stiffness > 1.34 m/s. Steatosis was determined by ultrasound. All participants underwent a clinical examination that included a comprehensive laboratory analysis and standardized interview about their medical and social history. We calculated weighted prevalence of fibrosis and determined clinical and demographic associations with significant fibrosis (with or without steatosis) and simple steatosis with no/minimal fibrosis using multinomial logistic regression. RESULTS: Fifty-nine participants were excluded due to unreliable pSWE findings or inconclusive ultrasound results, for a final analysis of 347 participants. The prevalence of significant fibrosis was 13.8%; most of these participants (37/42, 88.1%) had no evidence of viral hepatitis or heavy drinking. Levels of liver enzymes were associated with fibrosis and simple steatosis. Indicators of metabolic health (insulin resistance, triglycerides, and cholesterol) were significantly associated with simple steatosis. Fibrosis, but not simple steatosis, was significantly associated with of antibodies against HCV in plasma (odds ratio, 18.9; P = .0138) and non-significantly associated with reduced platelet count (odds ratio, 0.8 per 50x103/µL; 95% CI, 0.5-1.1). Multivariable analyses, as well as sensitivity analyses removing F4 fibrosis and viral or alcoholic etiologies, confirmed our results. CONCLUSION: We estimated the prevalence of fibrosis in a large population of Mexican American Hispanics using pSWE measurements. We found Mexican American Hispanics to have a higher prevalence of fibrosis compared to European and Asian populations, primarily attributable to metabolic disease.


Assuntos
Cirrose Hepática/epidemiologia , Cirrose Hepática/patologia , Americanos Mexicanos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Asiático , Estudos de Coortes , Técnicas de Imagem por Elasticidade , Feminino , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Prevalência , Texas/epidemiologia , População Branca , Adulto Jovem
7.
Prev Chronic Dis ; 13: E113, 2016 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-27560721

RESUMO

INTRODUCTION: Hispanic men have higher rates of illness and death from various chronic conditions than do non-Hispanic men. We aimed to characterize the health of Mexican American men living on the US-Mexico border in South Texas and elucidate indications of chronic disease in young men. METHODS: We sampled all male participants from the Cameron County Hispanic Cohort, an ongoing population-based cohort of Mexican Americans in Brownsville, Texas. We calculated descriptive statistics and stratified the sample into 3 age groups to estimate the prevalence of sociodemographic, behavioral, and clinical factors by age group and evaluated differences between age groups. RESULTS: Obesity prevalence was approximately 50% across all age groups (P = .83). Diabetes prevalence was high overall (26.8%), and 16.9% (95% confidence interval [CI], 10.1%-23.8%) of men younger than 35 had diabetes. More than 70% of these young men had elevated liver enzymes, and mean values of aspartate aminotransferase were significantly higher in younger men (45.0 u/L; 95% CI, 39.5-50.6 u/L) than in both older age groups. Less than 20% of young men had any form of health insurance. Current smoking was higher in young men than in men in the other groups, and the rate was higher than the national prevalence of current smoking among Hispanic men. CONCLUSIONS: We suggest a need for obesity and diabetes prevention programs and smoking cessation programs for men in this region. Opportunities exist to expand current intervention programs and tailor them to better reach this vulnerable population of young Hispanic men. Elevated liver enzymes in men younger than 35 suggest a substantial burden of liver abnormalities, a finding that warrants further study.


Assuntos
Diabetes Mellitus/etnologia , Seguro Saúde/estatística & dados numéricos , Hepatopatias/etnologia , Americanos Mexicanos/estatística & dados numéricos , Obesidade/etnologia , Fumar/etnologia , Adolescente , Adulto , Doença Crônica/etnologia , Estudos Transversais , Humanos , Testes de Função Hepática , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Texas/epidemiologia , Adulto Jovem
8.
JNCI Cancer Spectr ; 8(3)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38565262

RESUMO

Women with high mammographic density have an increased risk of breast cancer. They may be offered contrast-enhanced mammography to improve breast cancer screening performance. Using a cohort of women receiving contrast-enhanced mammography, we evaluated whether conventional and modified mammographic density measures were associated with breast cancer. Sixty-six patients with newly diagnosed unilateral breast cancer were frequency matched on the basis of age to 133 cancer-free control individuals. On low-energy craniocaudal contrast-enhanced mammograms (equivalent to standard mammograms), we measured quantitative mammographic density using CUMULUS software at the conventional intensity threshold ("Cumulus") and higher-than-conventional thresholds ("Altocumulus," "Cirrocumulus"). The measures were standardized to enable estimation of odds ratio per adjusted standard deviation (OPERA). In multivariable logistic regression of case-control status, only the highest-intensity measure (Cirrocumulus) was statistically significantly associated with breast cancer (OPERA = 1.40, 95% confidence interval = 1.04 to 1.89). Conventional Cumulus did not contribute to model fit. For women receiving contrast-enhanced mammography, Cirrocumulus mammographic density may better predict breast cancer than conventional quantitative mammographic density.


Assuntos
Neoplasias da Mama , Meios de Contraste , Mamografia , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Meios de Contraste/administração & dosagem , Estudos de Casos e Controles , Idoso , Densidade da Mama , Modelos Logísticos , Adulto , Razão de Chances , Mama/diagnóstico por imagem , Mama/patologia
9.
Cancer Res ; 84(15): 2533-2548, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38832928

RESUMO

Breast cancer includes several subtypes with distinct characteristic biological, pathologic, and clinical features. Elucidating subtype-specific genetic etiology could provide insights into the heterogeneity of breast cancer to facilitate the development of improved prevention and treatment approaches. In this study, we conducted pairwise case-case comparisons among five breast cancer subtypes by applying a case-case genome-wide association study (CC-GWAS) approach to summary statistics data of the Breast Cancer Association Consortium. The approach identified 13 statistically significant loci and eight suggestive loci, the majority of which were identified from comparisons between triple-negative breast cancer (TNBC) and luminal A breast cancer. Associations of lead variants in 12 loci remained statistically significant after accounting for previously reported breast cancer susceptibility variants, among which, two were genome-wide significant. Fine mapping implicated putative functional/causal variants and risk genes at several loci, e.g., 3q26.31/TNFSF10, 8q22.3/NACAP1/GRHL2, and 8q23.3/LINC00536/TRPS1, for TNBC as compared with luminal cancer. Functional investigation further identified rs16867605 at 8q22.3 as a SNP that modulates the enhancer activity of GRHL2. Subtype-informative polygenic risk scores (PRS) were derived, and patients with a high subtype-informative PRS had an up to two-fold increased risk of being diagnosed with TNBC instead of luminal cancers. The CC-GWAS PRS remained statistically significant after adjusting for TNBC PRS derived from traditional case-control GWAS in The Cancer Genome Atlas and the African Ancestry Breast Cancer Genetic Consortium. The CC-GWAS PRS was also associated with overall survival and disease-specific survival among patients with breast cancer. Overall, these findings have advanced our understanding of the genetic etiology of breast cancer subtypes, particularly for TNBC. Significance: The discovery of subtype-informative genetic risk variants for breast cancer advances our understanding of the etiologic heterogeneity of breast cancer, which could accelerate the identification of targets and personalized strategies for prevention and treatment.


Assuntos
Neoplasias da Mama , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Estudos de Casos e Controles , Fatores de Risco
10.
Radiat Res ; 200(4): 331-339, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37590492

RESUMO

Over 4 million survivors of breast cancer live in the United States, 35% of whom were treated before 2009. Approximately half of patients with breast cancer receive radiation therapy, which exposes the untreated contralateral breast to radiation and increases the risk of a subsequent contralateral breast cancer (CBC). Radiation oncology has strived to reduce unwanted radiation dose, but it is unknown whether a corresponding decline in actual dose received to the untreated contralateral breast has occurred. The purpose of this study was to evaluate trends in unwanted contralateral breast radiation dose to inform risk assessment of second primary cancer in the contralateral breast for long-term survivors of breast cancer. Individually estimated radiation absorbed doses to the four quadrants and areola central area of the contralateral breast were estimated for 2,132 women treated with radiation therapy for local/regional breast cancers at age <55 years diagnosed between 1985 and 2008. The two inner quadrant doses and two outer quadrant doses were averaged. Trends in dose to each of the three areas of the contralateral breast were evaluated in multivariable models. The population impact of reducing contralateral breast dose on the incidence of radiation-associated CBC was assessed by estimating population attributable risk fraction (PAR) in a multivariable model. The median dose to the inner quadrants of the contralateral breast was 1.70 Gy; to the areola, 1.20 Gy; and to the outer quadrants, 0.72 Gy. Ninety-two percent of patients received ≥1 Gy to the inner quadrants. For each calendar year of diagnosis, dose declined significantly for each location, most rapidly for the inner quadrants (0.04 Gy/year). Declines in dose were similar across subgroups defined by age at diagnosis and body mass index. The PAR for CBC due to radiation exposure >1 Gy for women <40 years of age was 17%. Radiation dose-reduction measures have reduced dose to the contralateral breast during breast radiation therapy. Reducing the dose to the contralateral breast to <1 Gy could prevent an estimated 17% of subsequent radiation-associated CBCs for women treated under 40 years of age. These dose estimates inform CBC surveillance for the growing number of breast cancer survivors who received radiation therapy as young women in recent decades. Continued reductions in dose to the contralateral breast could further reduce the incidence of radiation-associated CBC.


Assuntos
Neoplasias da Mama , Neoplasias Induzidas por Radiação , Segunda Neoplasia Primária , Feminino , Humanos , Estados Unidos , Pessoa de Meia-Idade , Neoplasias da Mama/radioterapia , Neoplasias da Mama/epidemiologia , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/etiologia , Fatores de Risco , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/complicações , Doses de Radiação
11.
J Natl Cancer Inst ; 114(4): 631-634, 2022 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-33779721

RESUMO

Evidence is mounting that cigarette smoking contributes to second primary contralateral breast cancer (CBC) risk. Whether radiation therapy (RT) interacts with smoking to modify this risk is unknown. In this multicenter, individually matched, case-control study, we examined the association between RT, smoking, and CBC risk. The study included 1521 CBC cases and 2212 controls with unilateral breast cancer, all diagnosed with first invasive breast cancer between 1985 and 2008 aged younger than 55 years. Absorbed radiation doses to contralateral breast regions were estimated with thermoluminescent dosimeters in tissue-equivalent anthropomorphic phantoms, and smoking history was collected by interview. Rate ratios (RRs) and 95% confidence intervals (CIs) for CBC risk were estimated by multivariable conditional logistic regression. There was no interaction between any measure of smoking with RT to increase CBC risk (eg, the interaction of continuous RT dose with smoking at first breast cancer diagnosis [ever/never]: RR = 1.00, 95% CI = 0.89 to 1.14; continuous RT dose with years smoked: RR = 1.00, 95% CI = 0.99 to 1.01; and continuous RT dose with lifetime pack-years: RR = 1.00, 95% CI = 0.99 to 1.01). There was no evidence that RT further increased CBC risk in young women with first primary breast cancer who were current smokers or had smoking history.


Assuntos
Neoplasias da Mama , Segunda Neoplasia Primária , Adulto , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/radioterapia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Segunda Neoplasia Primária/epidemiologia , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia
12.
NPJ Breast Cancer ; 7(1): 146, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34845211

RESUMO

To evaluate whether mammographic texture features were associated with second primary contralateral breast cancer (CBC) risk, we created a "texture risk score" using pre-treatment mammograms in a case-control study of 212 women with CBC and 223 controls with unilateral breast cancer. The texture risk score was associated with CBC (odds per adjusted standard deviation = 1.25, 95% CI 1.01-1.56) after adjustment for mammographic percent density and confounders. These results support the potential of texture features for CBC risk assessment of breast cancer survivors.

13.
JACC CardioOncol ; 3(3): 381-392, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34604798

RESUMO

BACKGROUND: Radiation therapy (RT) for breast cancer increases risk of coronary artery disease (CAD). Women treated for left- vs right-sided breast cancer receive greater heart radiation exposure, which may further increase this risk. The risk of radiation-associated CAD specifically among younger breast cancer survivors is not well defined. OBJECTIVES: The purpose of this study was to report CAD risk among participants in the Women's Environmental Cancer and Radiation Epidemiology Study. METHODS: A total of 1,583 women who were <55 years of age when diagnosed with breast cancer between 1985 and 2008 completed a cardiovascular health questionnaire. Risk of radiation-associated CAD was evaluated by comparing women treated with left-sided RT with women treated with right-sided RT using multivariable Cox proportional hazards models. Effect modification by treatment and cardiovascular risk factors was examined. RESULTS: In total, 517 women who did not receive RT and 94 women who had a pre-existing cardiovascular disease diagnosis were excluded, leaving 972 women eligible for analysis. Their median follow-up time was 14 years (range 1-29 years). The 27.5-year cumulative incidences of CAD for women receiving left- vs right-sided RT were 10.5% and 5.8%, respectively (P = 0.010). The corresponding HR of CAD for left- vs right-sided RT in the multivariable Cox model was 2.5 (95% CI: 1.3-4.7). There was no statistically significant effect modification by any factor evaluated. CONCLUSIONS: Young women treated with RT for left-sided breast cancer had over twice the risk of CAD compared with women treated with RT for right-sided breast cancer. Laterality of RT is independently associated with an increased risk of CAD and should be considered in survivorship care of younger breast cancer patients.

14.
Hepatol Commun ; 4(12): 1793-1801, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33305150

RESUMO

Diabetes is associated with liver disease and risk of hepatocellular carcinoma. In this study, we evaluated the association between liver fibrosis measured by transient elastography and four glucose metabolism measures in the Cameron County Hispanic Cohort, a population-based, randomly selected cohort of Mexican American Hispanics with high rates of diabetes and liver cancer. We measured liver fibrosis (a risk factor for hepatocellular carcinoma) in 774 well-characterized cohort participants using transient elastography. We evaluated the association of liver fibrosis with glycated hemoglobin (HbA1c), fasting blood glucose, insulin, and insulin resistance using multivariable linear regression models. In multivariable models, log-transformed HbA1c had the strongest association with liver fibrosis (ß = 0.37, 95% confidence interval [CI] 0.04-0.69, P = 0.038), after controlling for waist circumference, aspartate aminotransferase, alanine aminotransferase, liver fat, and other known confounders. The association was statistically significant among women (ß = 0.33, 95% CI 0.10-0.56, P = 0.009) and similar but nonsignificant among men (ß = 0.41, 95% CI -0.17 to 0.98, P = 0.593). Waist circumference, platelet count, aspartate transaminase, and liver steatosis were each associated with liver stiffness. Conclusions: Elevated HbA1c is associated with liver fibrosis, a key risk factor for HCC, particularly among women. Our results indicate that Mexican Americans with uncontrolled HbA1c may benefit from routine screening by liver elastography to identify individuals at risk of liver disease progression.

15.
JAMA Netw Open ; 2(9): e1912259, 2019 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-31560388

RESUMO

Importance: Radiation therapy for breast cancer is associated with increased risk of a second primary contralateral breast cancer, but the genetic factors modifying this association are not well understood. Objective: To determine whether a genetic risk score comprising single nucleotide polymorphisms in the nonhomologous end-joining DNA repair pathway is associated with radiation-associated contralateral breast cancer. Design, Setting, and Participants: This case-control study included a case group of women with contralateral breast cancer that was diagnosed at least 1 year after a first primary breast cancer who were individually matched to a control group of women with unilateral breast cancer. Inclusion criteria were receiving a first invasive breast cancer diagnosis prior to age 55 years between 1985 and 2008. Women were recruited through 8 population-based cancer registries in the United States, Canada, and Denmark as part of the Women's Environment, Cancer, and Radiation Epidemiology Studies I (November 2000 to August 2004) and II (March 2010 to December 2012). Data analysis was conducted from July 2017 to August 2019. Exposures: Stray radiation dose to the contralateral breast during radiation therapy for the first breast cancer. A novel genetic risk score comprised of genetic variants in the nonhomologous end-joining DNA repair pathway was considered the potential effect modifier, dichotomized as high risk if the score was above the median of 74 and low risk if the score was at or below the median. Main Outcomes and Measures: The main outcome was risk of contralateral breast cancer associated with stray radiation dose stratified by genetic risk score, age, and latency. Results: A total of 5953 women were approached for study participation, and 3732 women (62.7%) agreed to participate. The median (range) age at first diagnosis was 46 (23-54) years. After 5 years of latency or more, among women who received the first diagnosis when they were younger than 40 years, exposure to 1.0 Gy (to convert to rad, multiply by 100) or more of stray radiation was associated with a 2-fold increased risk of contralateral breast cancer compared with women who were not exposed (rate ratio, 2.0 [95% CI, 1.1-3.6]). The risk was higher among women with a genetic risk score above the median (rate ratio, 3.0 [95% CI, 1.1-8.1]), and there was no association among women with a genetic risk score below the median (rate ratio, 1.3 [95% CI, 0.5-3.7]). Among younger women with a high genetic risk score, the attributable increased risk for contralateral breast cancer associated with stray radiation dose was 28%. Conclusions and Relevance: This study found an increased risk of contralateral breast cancer that was attributable to stray radiation exposure among women with a high genetic risk score and who received a first breast cancer diagnosis when they were younger than 40 years after 5 years or more of latency. This genetic risk score may help guide treatment and surveillance for women with breast cancer.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias Induzidas por Radiação/patologia , Segunda Neoplasia Primária/induzido quimicamente , Radioterapia/efeitos adversos , Adulto , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/genética , Polimorfismo de Nucleotídeo Único , Medição de Risco , Fatores de Risco
16.
BMJ Open Diabetes Res Care ; 6(1): e000436, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29607048

RESUMO

OBJECTIVE: Prevalence of type 2 diabetes varies by region and ancestry. However, most guidelines for the prevention of diabetes mellitus (DM) are based on European or non-Hispanic white populations. Two ethnic minority populations-Mexican Americans (MAs) in Texas, USA, and South Indians (SIs) in Tamil Nadu, India-have an increasing prevalence of DM. We aimed to understand the metabolic correlates of DM in these populations to improve risk stratification and DM prevention. RESEARCH DESIGN AND METHODS: The Cameron County Hispanic Cohort (CCHC; n=3023) served as the MA sample, and the Population Study of Urban, Rural, and Semi-Urban Regions for the Detection of Endovascular Disease (PURSE; n=8080) served as the SI sample. Using design-based methods, we calculated the prevalence of DM and metabolic comorbidities in each cohort. We determined the association of DM with metabolic phenotypes to evaluate the relative contributions of obesity and metabolic health to the prevalence of DM. RESULTS: In the CCHC (overall DM prevalence 26.2%), good metabolic health was associated with lower prevalence of DM, across age groups, regardless of obesity. In PURSE (overall prevalence 27.6%), probability of DM was not strongly associated with metabolic phenotypes, although DM prevalence was high in older age groups irrespective of metabolic health. CONCLUSION: Our study provides robust, population-based data to estimate the prevalence of DM and its associations with metabolic health. Our results demonstrate differences in metabolic phenotypes in DM, which should inform DM prevention guidelines in non-European populations.

17.
Oncotarget ; 9(50): 29495-29507, 2018 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-30034633

RESUMO

The incidence of hepatocellular carcinoma (HCC) associated with non-alcoholic fatty liver disease (NAFLD) is rapidly increasing. We aimed to elucidate the genetic basis of NAFLD-associated HCC and identify candidate targets for chemoprevention. Twenty HCC tumors, distant liver and matched tails from mice with hepatocyte-deletion of Pten (HepPten-) were subjected to whole-exome sequencing. A total of 162 genes with somatic non-synonymous single nucleotide variants or exonic small insertions and deletions in tumors were identified. Ingenuity Pathway Analysis of these 162 genes, further identified Toll-like receptor (TLR) 4, a key mediator of proinflammatory responses, and resatorvid, a TLR4 inhibitor, as the main causal networks of this dataset. Resatorvid treatment strongly prevented HCC development in these mice (p < 0.001). Remarkably, HCC patients with high tumoral TLR4 mRNA expression were more likely to be diagnosed with NAFLD and obese. TLR4 mRNA expression positively correlated with IL-6 and IL-10 mRNA expression in HCC tumors and the correlation was stronger in obese HCC patients. We have identified tumor mutation signatures and associated causal networks in NAFLD-associated HCC in HepPten- mice and further demonstrated the important role of TLR4 in promoting HCC development. This study also identified IL-6 and IL-10 as markers of TLR4 activation in HCC and subjects with NAFLD and obesity as the target population who would benefit from TLR4 inhibition treatment for HCC chemoprevention.

18.
Hepatol Commun ; 2(6): 718-731, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29881823

RESUMO

Telomerase reverse transcriptase (TERT) mutation is the most frequent genetic alteration in hepatocellular carcinoma (HCC). Our aims were to investigate whether TERT mutations can be detected in circulating cell-free DNA (cfDNA) of patients with HCC and/or cirrhosis and characterize clinical parameters associated with these mutations. We retrieved data on TERT C228T and C250T promoter mutations in 196 HCCs from The Cancer Genome Atlas. We measured these TERT mutations in plasma cfDNA in 218 patients with HCC and 81 patients with cirrhosis without imaging evidence of HCC. The prevalence of TERT mutations in The Cancer Genome Atlas HCC specimens was 44.4%. TERT mutations were detected with similar prevalence (47.7%) in plasma cfDNAs from 218 patients with HCC. TERT mutations, either within the HCC or in cfDNA, were associated with male sex, hepatitis C virus (HCV), alcoholic cirrhosis, family history of cancer, and poor prognosis. The high prevalence of TERT mutations in HCCs in male patients with cirrhosis caused by HCV and/or alcohol was confirmed in an independent set of HCCs (86.6%). Finally, TERT mutations were detected in cfDNA of 7 out of 81 (8.6%) patients with cirrhosis without imaging evidence of HCC, including 5 male patients with cirrhosis due to HCV and/or alcohol. Genes involved in xenobiotic and alcohol metabolism were enriched in HCCs with TERT mutations, and vitamin K2 was identified as an upstream regulator. Conclusion: TERT mutations are detectable in plasma cfDNA. Long-term imaging surveillance of patients with cirrhosis with cfDNA TERT mutations without evidence of HCC is required to assess their potential as early biomarkers of HCC. (Hepatology Communications 2018;2:718-731).

19.
J Osteoporos ; 2018: 7153021, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29862008

RESUMO

Altered bone quality, caused by underlying metabolic changes of type 2 diabetes (T2D), has been hypothesized to cause altered bone strength and turnover leading to increased fracture risk in T2D patients. Current understanding about changes in bone turnover markers in T2D patients is mainly based on studies focused on Caucasian men and women. However, Hispanic populations have the highest prevalence of both T2D and osteoporosis in the US. We investigated associations of glycemic control (in terms of glycated hemoglobin [HbA1c]) and bone turnover rate in 69 older (≥50 years) Mexican American Cameron County Hispanic Cohort (CCHC) participants with T2D. Multivariable analyses were conducted to assess the associations between HbA1c (%), serum osteocalcin (OC), and serum sclerostin. In agreement with published reports from other racial/ethnic populations, our study found that lower bone turnover (indicated by lower serum OC) occurred in Mexican American men with T2D who had poorer glycemic control. For the women in our study, we found no significant association between glycemic control and OC. In contrast, HbA1c was positively associated with sclerostin for women, with near significance (p = 0.07), while no association was found in men. We recommend screening Mexican American individuals with T2D, specifically those with poor glycemic control, for bone loss and fracture risk.

20.
Cancer Prev Res (Phila) ; 11(2): 103-112, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29089331

RESUMO

We aimed to determine whether aflatoxin dietary exposure plays a role in the high incidence of hepatocellular carcinoma (HCC) observed among Hispanics in South Texas. We measured TP53R249S somatic mutation, hallmark of aflatoxin etiology in HCC, using droplet digital PCR and RFLP. TP53R249S mutation was detected in 3 of 41 HCC tumors from Hispanics in South Texas (7.3%). We also measured TP53R249S mutation in plasma cell-free DNA (cfDNA) from 218 HCC patients and 96 Hispanic subjects with advanced fibrosis or cirrhosis, from South Texas. The mutation was detected only in Hispanic and Asian HCC patients, and patients harboring TP53R249S mutation were significantly younger and had a shorter overall survival. The mutation was not detected in any Hispanic subject with advanced fibrosis or cirrhosis. Genes involved in cell-cycle control of chromosomal replication and in BRCA1-dependent DNA damage response were enriched in HCCs with TP53R249S mutation. The E2F1 family members, E2F1 and E2F4, were identified as upstream regulators. TP53R249S mutation was detected in 5.7% to 7.3% of Hispanics with HCC in South Texas. This mutation was associated with a younger age and worse prognosis. TP53R249S was however not detected in Hispanics in South Texas with cirrhosis or advanced fibrosis. Aflatoxin exposure may contribute to a small number of HCCs in Hispanics in South Texas, but the detection of TP53R249S mutation in plasma cfDNA is not a promising biomarker of risk assessment for HCC in subjects with cirrhosis or advanced fibrosis in this population. Cancer Prev Res; 11(2); 103-12. ©2017 AACR.


Assuntos
Aflatoxinas/administração & dosagem , Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Hispânico ou Latino/genética , Neoplasias Hepáticas/genética , Mutação , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/patologia , Ácidos Nucleicos Livres , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Venenos/administração & dosagem , Prevalência , Prognóstico , Texas/epidemiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA