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1.
Cancers (Basel) ; 13(21)2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34771561

RESUMO

Smoking is associated with a moderate increased risk of Hodgkin and follicular lymphoma. To understand why, we examined lymphoma-related biomarker levels among 134 smoking and non-smoking twins (67 pairs) ascertained from the Finnish Twin Cohort. Previously collected frozen serum samples were tested for cotinine to validate self-reported smoking history. In total, 27 immune biomarkers were assayed using the Luminex Multiplex platform (R & D Systems). Current and non-current smokers were defined by a serum cotinine concentration of >3.08 ng/mL and ≤3.08 ng/mL, respectively. Associations between biomarkers and smoking were assessed using linear mixed models to estimate beta coefficients and standard errors, adjusting for age, sex and twin pair as a random effect. There were 55 never smokers, 43 current smokers and 36 former smokers. CCL17/TARC, sgp130, haptoglobin, B-cell activating factor (BAFF) and monocyte chemoattractant protein-1 (MCP1) were significantly (p < 0.05) associated with current smoking and correlated with increasing cotinine concentrations (Ptrend < 0.05). The strongest association was observed for CCL17/TARC (Ptrend = 0.0001). Immune biomarker levels were similar in former and never smokers. Current smoking is associated with increased levels of lymphoma-associated biomarkers, suggesting a possible mechanism for the link between smoking and risk of these two B-cell lymphomas.

2.
Cancer Res ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34759001

RESUMO

Longitudinal studies of SARS-CoV-2 vaccine-induced immune responses in cancer patients are needed to optimize clinical care. In a prospective cohort study of 366 (291 vaccinated) patients, we measured antibody levels [anti-spike (IgG-(S-RBD)) and anti-nucleocapsid immunoglobulin] at three timepoints. Antibody level trajectories and frequency of breakthrough infections were evaluated by tumor type and timing of treatment relative to vaccination. IgG-(S-RBD) at peak response (median=42 days after dose 2) was higher (p=0.002) and remained higher after 4-6 months (p=0.003) in patients receiving mRNA-1273 compared to BNT162b2. Patients with solid tumors attained higher peak levels (p=0.001) and sustained levels after 4-6 months (p<0.001) compared to those with hematologic malignancies. B-cell targeted treatment reduced peak (p=0.001) and sustained antibody responses (p=0.003). Solid tumor patients receiving immune checkpoint inhibitors before vaccination had lower sustained antibody levels than those who received treatment after vaccination (p=0.043). Two (0.69%) vaccinated and one (1.9%) unvaccinated patient had severe COVID-19 illness during follow-up. Our study shows variation in sustained antibody responses across cancer populations receiving various therapeutic modalities with important implications for vaccine booster timing and patient selection.

4.
J Transl Genet Genom ; 5: 200-217, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34622145

RESUMO

Aim: Recessive genetic variation is thought to play a role in non-Hodgkin lymphoma (NHL) etiology. Runs of homozygosity (ROH), defined based on long, continuous segments of homozygous SNPs, can be used to estimate both measured and unmeasured recessive genetic variation. We sought to examine genome-wide homozygosity and NHL risk. Methods: We used data from eight genome-wide association studies of four common NHL subtypes: 3061 chronic lymphocytic leukemia (CLL), 3814 diffuse large B-cell lymphoma (DLBCL), 2784 follicular lymphoma (FL), and 808 marginal zone lymphoma (MZL) cases, as well as 9374 controls. We examined the effect of homozygous variation on risk by: (1) estimating the fraction of the autosome containing runs of homozygosity (FROH); (2) calculating an inbreeding coefficient derived from the correlation among uniting gametes (F3); and (3) examining specific autosomal regions containing ROH. For each, we calculated beta coefficients and standard errors using logistic regression and combined estimates across studies using random-effects meta-analysis. Results: We discovered positive associations between FROH and CLL (ß = 21.1, SE = 4.41, P = 1.6 × 10-6) and FL (ß = 11.4, SE = 5.82, P = 0.02) but not DLBCL (P = 1.0) or MZL (P = 0.91). For F3, we observed an association with CLL (ß = 27.5, SE = 6.51, P = 2.4 × 10-5). We did not find evidence of associations with specific ROH, suggesting that the associations observed with FROH and F3 for CLL and FL risk were not driven by a single region of homozygosity. Conclusion: Our findings support the role of recessive genetic variation in the etiology of CLL and FL; additional research is needed to identify the specific loci associated with NHL risk.

6.
Prev Med ; 153: 106860, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34687733

RESUMO

Despite demonstrated efficacy of vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19), widespread hesitancy to vaccination persists. Improved knowledge regarding frequency, severity, and duration of vaccine-associated symptoms may help reduce hesitancy. In this prospective observational study, we studied 1032 healthcare workers who received both doses of the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine and completed post-vaccine symptom surveys both after dose 1 and after dose 2. We defined appreciable post-vaccine symptoms as those of at least moderate severity and lasting at least 2 days. We found that symptoms were more frequent following the second vaccine dose than the first (74% vs. 60%, P < 0.001), with >80% of all symptoms resolving within 2 days. The most common symptom was injection site pain, followed by fatigue and malaise. Overall, 20% of participants experienced appreciable symptoms after dose 1 and 30% after dose 2. In multivariable analyses, female sex was associated with greater odds of appreciable symptoms after both dose 1 (OR, 95% CI 1.73, 1.19-2.51) and dose 2 (1.76, 1.28-2.42). Prior COVID-19 was also associated with appreciable symptoms following dose 1, while younger age and history of hypertension were associated with appreciable symptoms after dose 2. We conclude that most post-vaccine symptoms are reportedly mild and last <2 days. Appreciable post-vaccine symptoms are associated with female sex, prior COVID-19, younger age, and hypertension. This information can aid clinicians in advising patients on the safety and expected symptomatology associated with vaccination.


Assuntos
COVID-19 , SARS-CoV-2 , Vacinas contra COVID-19 , Feminino , Humanos , RNA Mensageiro , Vacinação
7.
Cancer Epidemiol Biomarkers Prev ; 30(12): 2286-2293, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34548330

RESUMO

BACKGROUND: The etiology of non-Hodgkin lymphoma (NHL) in children and in adolescents and young adults (AYA) is not well understood. METHODS: We evaluated potential associations between mode of delivery, birth characteristics, and NHL risk in a population-based case-control study, which included 3,064 cases of NHL [490 with Burkitt lymphoma, 981 with diffuse large B-cell lymphoma (DLBCL), and 978 with T-cell NHL) diagnosed at the age of 0 to 37 years in California during 1988 to 2015 and 153,200 controls frequency matched on year of birth. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from an unconditional multivariable logistic regression model that included year of birth and birth characteristics. RESULTS: Individuals born via cesarean section had a decreased risk of pediatric Burkitt lymphoma (age 0-14 years; OR = 0.71, 95% CI: 0.51-0.99) and pediatric T-cell NHL (OR = 0.73, 95% CI: 0.55-0.97) compared with those born vaginally. Having a birth order of second (OR = 0.73, 95% CI: 0.57-0.93) or third or higher (OR = 0.76, 95% CI: 0.58-0.99) was associated with a lower risk of pediatric T-cell NHL compared with first-borns. AYA (age 15-37 years) with a heavier birthweight had an elevated risk of DLBCL (OR for each kg = 1.16, 95% CI: 1.00-1.35). Associations between other birth characteristics, including plurality, maternal age, maternal education, and NHL risk, also exhibited variations across subgroups based on age of diagnosis and histologic subtype. CONCLUSIONS: These findings support a role of mode of delivery and birth characteristics in the etiology of early-onset NHL. IMPACT: This study underscores the etiologic heterogeneity of early-onset NHL.

8.
Horm Behav ; 136: 105054, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34488063

RESUMO

Comparing twins from same- and opposite-sex pairs can provide information on potential sex differences in a variety of outcomes, including socioeconomic-related outcomes such as educational attainment. It has been suggested that this design can be applied to examine the putative role of intrauterine exposure to testosterone for educational attainment, but the evidence is still disputed. Thus, we established an international database of twin data from 11 countries with 88,290 individual dizygotic twins born over 100 years and tested for differences between twins from same- and opposite-sex dizygotic pairs in educational attainment. Effect sizes with 95% confidence intervals (CI) were estimated by linear regression models after adjusting for birth year and twin study cohort. In contrast to the hypothesis, no difference was found in women (ß = -0.05 educational years, 95% CI -0.11, 0.02). However, men with a same-sex co-twin were slightly more educated than men having an opposite-sex co-twin (ß = 0.14 educational years, 95% CI 0.07, 0.21). No consistent differences in effect sizes were found between individual twin study cohorts representing Europe, the USA, and Australia or over the cohorts born during the 20th century, during which period the sex differences in education reversed favoring women in the latest birth cohorts. Further, no interaction was found with maternal or paternal education. Our results contradict the hypothesis that there would be differences in the intrauterine testosterone levels between same-sex and opposite-sex female twins affecting education. Our findings in men may point to social dynamics within same-sex twin pairs that may benefit men in their educational careers.

9.
PLoS One ; 16(6): e0253549, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34166416

RESUMO

The objective of this study was to use available data on the prevalence of COVID-19 risk factors in subpopulations and epidemic dynamics at the population level to estimate probabilities of severe illness and the case and infection fatality rates (CFR and IFR) stratified across subgroups representing all combinations of the risk factors age, comorbidities, obesity, and smoking status. We focus on the first year of the epidemic in Los Angeles County (LAC) (March 1, 2020-March 1, 2021), spanning three epidemic waves. A relative risk modeling approach was developed to estimate conditional effects from available marginal data. A dynamic stochastic epidemic model was developed to produce time-varying population estimates of epidemic parameters including the transmission and infection observation rate. The epidemic and risk models were integrated to produce estimates of subpopulation-stratified probabilities of disease progression and CFR and IFR for LAC. The probabilities of disease progression and CFR and IFR were found to vary as extensively between age groups as within age categories combined with the presence of absence of other risk factors, suggesting that it is inappropriate to summarize epidemiological parameters for age categories alone, let alone the entire population. The fine-grained subpopulation-stratified estimates of COVID-19 outcomes produced in this study are useful in understanding disparities in the effect of the epidemic on different groups in LAC, and can inform analyses of targeted subpopulation-level policy interventions.


Assuntos
COVID-19/mortalidade , COVID-19/transmissão , Modelos Biológicos , SARS-CoV-2 , California/epidemiologia , Feminino , Humanos , Masculino , Medição de Risco
10.
Cells ; 10(2)2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33671849

RESUMO

Bilirubin, an endogenous antioxidant, may play a protective role in cancer development. We applied two-sample Mendelian randomization to investigate whether genetically raised bilirubin levels are causally associated with the risk of ten cancers (pancreas, kidney, endometrium, ovary, breast, prostate, lung, Hodgkin's lymphoma, melanoma, and neuroblastoma). The number of cases and their matched controls of European descent ranged from 122,977 and 105,974 for breast cancer to 1200 and 6417 for Hodgkin's lymphoma, respectively. A total of 115 single-nucleotide polymorphisms (SNPs) associated (p < 5 × 10-8) with circulating total bilirubin, extracted from a genome-wide association study in the UK Biobank, were used as instrumental variables. One SNP (rs6431625) in the promoter region of the uridine-diphosphoglucuronate glucuronosyltransferase1A1 (UGT1A1) gene explained 16.9% and the remaining 114 SNPs (non-UGT1A1 SNPs) explained 3.1% of phenotypic variance in circulating bilirubin levels. A one-standarddeviation increment in circulating bilirubin (≈ 4.4 µmol/L), predicted by non-UGT1A1 SNPs, was inversely associated with risk of squamous cell lung cancer and Hodgkin's lymphoma (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.73-0.99, P 0.04 and OR 0.64, 95% CI 0.42-0.99, p 0.04, respectively), which was confirmed after removing potential pleiotropic SNPs. In contrast, a positive association was observed with the risk of breast cancer after removing potential pleiotropic SNPs (OR 1.12, 95% CI 1.04-1.20, p 0.002). There was little evidence for robust associations with the other seven cancers investigated. Genetically raised bilirubin levels were inversely associated with risk of squamous cell lung cancer as well as Hodgkin's lymphoma and positively associated with risk of breast cancer. Further studies are required to investigate the utility of bilirubin as a low-cost clinical marker to improve risk prediction for certain cancers.


Assuntos
Bilirrubina/genética , Neoplasias da Mama/genética , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único/genética , Biomarcadores/análise , Neoplasias da Mama/tratamento farmacológico , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana/métodos , Fatores de Risco
11.
medRxiv ; 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33367291

RESUMO

Background: Health disparities have emerged with the COVID-19 epidemic because the risk of exposure to infection and the prevalence of risk factors for severe outcomes given infection vary within and between populations. However, estimated epidemic quantities such as rates of severe illness and death, the case fatality rate (CFR), and infection fatality rate (IFR), are often expressed in terms of aggregated population-level estimates due to the lack of epidemiological data at the refined subpopulation level. For public health policy makers to better address the pandemic, stratified estimates are necessary to investigate the potential outcomes of policy scenarios targeting specific subpopulations. Methods: We develop a framework for using available data on the prevalence of COVID-19 risk factors (age, comorbidities, BMI, smoking status) in subpopulations, and epidemic dynamics at the population level and stratified by age, to estimate subpopulation-stratified probabilities of severe illness and the CFR (as deaths over observed infections) and IFR (as deaths over estimated total infections) across risk profiles representing all combinations of risk factors including age, comorbidities, obesity class, and smoking status. A dynamic epidemic model is integrated with a relative risk model to produce time-varying subpopulation-stratified estimates. The integrated model is used to analyze dynamic outcomes and parameters by population and subpopulation, and to simulate alternate policy scenarios that protect specific at-risk subpopulations or modify the population-wide transmission rate. The model is calibrated to data from the Los Angeles County population during the period March 1 - October 15 2020. Findings: We estimate a rate of 0.23 (95% CI: 0.13,0.33) of infections observed before April 15, which increased over the epidemic course to 0.41 (0.11,0.69). Overall population-average IFR( t ) estimates for LAC peaked at 0.77% (0.38%,1.15%) on May 15 and decreased to 0.55% (0.24%,0.90%) by October 15. The population-average IFR( t ) stratified by age group varied extensively across subprofiles representing each combination of the additional risk factors considered (comorbidities, BMI, smoking). We found median IFRs ranging from 0.009%-0.04% in the youngest age group (0-19), from 0.1%-1.8% for those aged 20-44, 0.36%-4.3% for those aged 45-64, and 1.02%-5.42% for those aged 65+. In the group aged 65+ for which the rate of unobserved infections is likely much lower, we find median CFRs in the range 4.4%-23.45%. The initial societal lockdown period avoided overwhelming healthcare capacity and greatly reduced the observed death count. In comparative scenario analysis, alternative policies in which the population-wide transmission rate is reduced to a moderate and sustainable level of non-pharmaceutical interventions (NPIs) would not have been sufficient to avoid overwhelming healthcare capacity, and additionally would have exceeded the observed death count. Combining the moderate NPI policy with stringent protection of the at-risk subpopulation of individuals 65+ would have resulted in a death count similar to observed levels, but hospital counts would have approached capacity limits. Interpretation: The risk of severe illness and death of COVID-19 varies tremendously across subpopulations and over time, suggesting that it is inappropriate to summarize epidemiological parameters for the entire population and epidemic time period. This includes variation not only across age groups, but also within age categories combined with other risk factors analyzed in this study (comorbidities, obesity status, smoking). In the policy analysis accounting for differences in IFR across risk groups in comparing the control of infections and protection of higher risk groups, we find that the strict initial lockdown period in LAC was effective because it both reduced overall transmission and protected individuals at greater risk, resulting in preventing both healthcare overload and deaths. While similar numbers of deaths as observed in LAC could have been achieved with a more moderate NPI policy combined with greater protection of individuals 65+, this would have come at the expense of overwhelming the healthcare system. In anticipation of a continued rise in cases in LAC this winter, policy makers need to consider the trade offs of various policy options on the numbers of the overall population that may become infected, severely ill, and that die when considering policies targeted at subpopulations at greatest risk of transmitting infection and at greatest risk for developing severe outcomes.

12.
Cancer Epidemiol ; 69: 101824, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33039726

RESUMO

BACKGROUND: Although there is some evidence of positive associations between both the glycemic index (GI) and glycemic load (GL) with cancer risk, the relationships with lung cancer risk remain largely unexplored. We evaluated the associations between GI and GL with lung cancer. METHODS: The analyses were performed using data from a population-based case-control study recruited between 1999 and 2004 in Los Angeles County. Dietary factors were collected from 593 incident lung cancer cases and 1026 controls using a modified food frequency questionnaire. GI and GL were estimated using a food composition table. Adjusted odds ratios (ORs) and 95 % confidence intervals (CI) were estimated using unconditional logistic regression adjusting for potential confounders. RESULTS: Dietary GI was positively associated with lung cancer (OR for upper vs. lower tertile = 1.62; 95 % CI: 1.17, 2.25). For histologic subtypes, positive associations were observed between GI and adenocarcinoma (OR for upper vs. lower tertile = 1.82; 95 % CI: 1.22, 2.70) and small cell carcinoma (OR for upper vs. lower tertile = 2.68; 95 % CI: 1.25, 5.74). No clear association between GL and lung cancer was observed. CONCLUSION: These findings suggest that high dietary GI was associated with increased lung cancer risk, and the positive associations were observed for both lung adenocarcinoma and small cell lung carcinoma. Replication in an independent dataset is merited for a broader interpretation of our results.


Assuntos
Índice Glicêmico/genética , Carga Glicêmica/genética , Neoplasias Pulmonares/epidemiologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Los Angeles , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
13.
Nat Rev Dis Primers ; 6(1): 61, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32703953

RESUMO

Hodgkin lymphoma (HL) is a B cell lymphoma characterized by few malignant cells and numerous immune effector cells in the tumour microenvironment. The incidence of HL is highest in adolescents and young adults, although HL can affect elderly individuals. Diagnosis is based on histological and immunohistochemical analyses of tissue from a lymph node biopsy; the tissue morphology and antigen expression profile enable classification into one of the four types of classic HL (nodular sclerosis, mixed cellularity, lymphocyte-depleted or lymphocyte-rich HL), which account for the majority of cases, or nodular lymphocyte-predominant HL. Although uncommon, HL remains a crucial test case for progress in cancer treatment. HL was among the first systemic neoplasms shown to be curable with radiation therapy and multiagent chemotherapy. The goal of multimodality therapy is to minimize lifelong residual treatment-associated toxicity while maintaining high levels of effectiveness. Recurrent or refractory disease can be effectively treated or cured with high-dose chemotherapy followed by autologous haematopoietic stem cell transplantation, and prospective trials have demonstrated the potency of immunotherapeutic approaches with antibody-drug conjugates and immune checkpoint inhibitors. This Primer explores the wealth of information that has been assembled to understand HL; these updated observations verify that HL investigation and treatment remain at the leading edge of oncological research.


Assuntos
Doença de Hodgkin/diagnóstico , Doença de Hodgkin/terapia , Fatores Etários , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/fisiopatologia , Doenças Genéticas Inatas/terapia , Herpesvirus Humano 4/patogenicidade , Doença de Hodgkin/fisiopatologia , Humanos , Incidência , Estadiamento de Neoplasias/métodos
14.
Blood Adv ; 4(12): 2789-2797, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32569378

RESUMO

So far, 23 germline susceptibility loci have been associated with multiple myeloma (MM) risk. It is unclear whether the genetic variation associated with MM susceptibility also predisposes to its precursor, monoclonal gammopathy of undetermined significance (MGUS). Leveraging 2434 MM cases, 754 MGUS cases, and 2 independent sets of controls (2567/879), we investigated potential shared genetic susceptibility of MM and MGUS by (1) performing MM and MGUS genome-wide association studies (GWAS); (2) validating the association of a polygenic risk score (PRS) based on 23 established MM loci (MM-PRS) with risk of MM, and for the first time with MGUS; and (3) examining genetic correlation of MM and MGUS. Heritability and genetic estimates yielded 17% (standard error [SE] ±0.04) and 15% (SE ±0.11) for MM and MGUS risk, respectively, and a 55% (SE ±0.30) genetic correlation. The MM-PRS was associated with risk of MM when assessed continuously (odds ratio [OR], 1.17 per SD; 95% confidence interval [CI], 1.13-1.21) or categorically (OR, 1.70; 95% CI, 1.38-2.09 for highest; OR, 0.71; 95% CI, 0.55-0.90 for lowest compared with middle quintile). The MM-PRS was similarly associated with MGUS (OR, 1.19 per SD; 95% CI, 1.14-1.26 as a continuous measure, OR, 1.77, 95%CI: 1.29-2.43 for highest and OR, 0.70, 95%CI: 0.50-0.98 for lowest compared with middle quintile). MM and MGUS associations did not differ by age, sex, or MM immunoglobulin isotype. We validated a 23-SNP MM-PRS in an independent series of MM cases and provide evidence for its association with MGUS. Our results suggest shared common genetic susceptibility to MM and MGUS.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Gamopatia Monoclonal de Significância Indeterminada/epidemiologia , Gamopatia Monoclonal de Significância Indeterminada/genética , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/genética , Razão de Chances
15.
Sci Rep ; 10(1): 7974, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409744

RESUMO

Genetic factors explain a major proportion of human height variation, but differences in mean stature have also been found between socio-economic categories suggesting a possible effect of environment. By utilizing a classical twin design which allows decomposing the variation of height into genetic and environmental components, we tested the hypothesis that environmental variation in height is greater in offspring of lower educated parents. Twin data from 29 cohorts including 65,978 complete twin pairs with information on height at ages 1 to 69 years and on parental education were pooled allowing the analyses at different ages and in three geographic-cultural regions (Europe, North America and Australia, and East Asia). Parental education mostly showed a positive association with offspring height, with significant associations in mid-childhood and from adolescence onwards. In variance decomposition modeling, the genetic and environmental variance components of height did not show a consistent relation to parental education. A random-effects meta-regression analysis of the aggregate-level data showed a trend towards greater shared environmental variation of height in low parental education families. In conclusion, in our very large dataset from twin cohorts around the globe, these results provide only weak evidence for the study hypothesis.


Assuntos
Estatura , Meio Ambiente , Interação Gene-Ambiente , Patrimônio Genético , Poder Familiar , Pais , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pais/educação , Locos de Características Quantitativas , Característica Quantitativa Herdável , Adulto Jovem
16.
Breast Cancer Res Treat ; 182(2): 451-463, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32468338

RESUMO

OBJECTIVE: To investigate the association between gut microbiome with breast tumor characteristics (receptor status, stage and grade) and known breast cancer risk factors. METHODS: In a pilot cross-sectional study of 37 incident breast cancer patients, fecal samples collected prior to chemotherapy were analyzed by 16S ribosomal RNA (rRNA) gene-based sequencing protocol. Alpha diversity and specific taxa by tumor characteristics and breast cancer risk factors were tested by Wilcoxon rank sum test, and by differential abundance analysis, using a zero-inflated negative binomial regression model with adjustment for total counts, age and race/ethnicity. RESULTS: There were no significant alpha diversity or phyla differences by estrogen/progesterone receptor status, tumor grade, stage, parity and body mass index. However, women with human epidermal growth factor receptor 2 positive (HER2+) (n = 12) compared to HER2- (n = 25) breast cancer showed 12-23% lower alpha diversity [number of species (OTU) p = 0.033, Shannon index p = 0.034], lower abundance of Firmicutes (p = 0.005) and higher abundance of Bacteroidetes (p = 0.089). Early menarche (ages ≤ 11) (n = 11) compared with later menarche (ages ≥ 12) (n = 26) was associated with lower OTU (p = 0.036), Chao1 index (p = 0.020) and lower abundance of Firmicutes (p = 0.048). High total body fat (TBF) (> 46%) (n = 12) compared to lower (≤ 46%) TBF was also associated with lower Chao 1 index (p = 0.011). There were other significant taxa abundance differences by HER2 status, menarche age, as well as other tumor and breast cancer risk factors. CONCLUSIONS AND RELEVANCE: Further studies are needed to identify characteristics of the human microbiome and the interrelationships between breast cancer hormone receptor status and established breast cancer risk factors.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/epidemiologia , Mama/patologia , Microbioma Gastrointestinal/fisiologia , Adulto , Fatores Etários , Idoso , Bacteroidetes/genética , Bacteroidetes/isolamento & purificação , Índice de Massa Corporal , Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Estudos Transversais , DNA Bacteriano/isolamento & purificação , Fezes/microbiologia , Feminino , Firmicutes/genética , Firmicutes/isolamento & purificação , Humanos , Menarca/fisiologia , Pessoa de Meia-Idade , Paridade/fisiologia , Projetos Piloto , RNA Ribossômico 16S/genética , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Fatores de Risco
17.
JCO Oncol Pract ; 16(10): e1169-e1180, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32469686

RESUMO

PURPOSE: Multiple myeloma (MM) treatment has changed tremendously, with significant improvement in patient out-comes. One group with a suboptimal benefit is patients with high-risk cytogenetics, as tested by conventional karyotyping or fluorescence in situ hybridization (FISH). Methodology for these tests has been published, but not necessarily standardized. METHODS: We address variability in the testing and reporting methodology for MM cytogenetics in the United States using the ongoing African American Multiple Myeloma Study (AAMMS). We evaluated clinical and cytogenetic data from 1,221 patients (1,161 with conventional karyotyping and 976 with FISH) tested between 1998 and 2016 across 58 laboratories nationwide. RESULTS: Interlab and intralab variability was noted for the number of cells analyzed for karyotyping, with a significantly higher number of cells analyzed in patients in whom cytogenetics were normal (P 5.0025). For FISH testing, CD138-positive cell enrichment was used in 29.7% of patients and no enrichment in 50% of patients, whereas the remainder had unknown status. A significantly smaller number of cells was analyzed for patients in which CD138 cell enrichment was used compared with those without such enrichment (median, 50 v 200; P, .0001). A median of 7 loci probes (range, 1-16) were used for FISH testing across all laboratories, with variability in the loci probed even within a given laboratory. Chromosome 13-related abnormalities were the most frequently tested abnormality (n5956; 97.9%), and t(14;16) was the least frequently tested abnormality (n 5 119; 12.2%). CONCLUSIONS: We report significant variability in cytogenetic testing across the United States for MM, potentially leading to variability in risk stratification, with possible clinical implications and personalized treatment approaches.


Assuntos
Análise Citogenética/normas , Mieloma Múltiplo , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Estados Unidos
19.
Cancer Causes Control ; 31(5): 451-462, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32124188

RESUMO

PURPOSE: We explored the interaction between non-Hodgkin lymphoma (NHL), infectious mononucleosis (IM) history, and immune-related genotypes in a pooled case-control analysis. METHODS: A total of 7,926 NHL patients and 10,018 controls from 12 case-control studies were included. Studies were conducted during various time periods between 1988 and 2008, and participants were 17-96 years of age at the time of ascertainment/recruitment. Self-reported IM history and immune response genotypes were provided by the InterLymph Data Coordinating Center at Mayo Clinic. Odds ratios (OR) were estimated using multivariate logistic regression, and interactions were estimated using the empirical Bayes method. PACT was used to account for multiple comparisons. RESULTS: There was evidence of an interaction effect between IM history and two variants on T-cell lymphoma (TCL) risk: rs1143627 in interleukin-1B (IL1B) (pinteraction = 0.04, ORinteraction = 0.09, 95% confidence interval [CI] 0.01, 0.87) and rs1800797 in interleukin-6 (IL6) (pinteraction = 0.03, ORinteraction = 0.08, 95% CI 0.01, 0.80). Neither interaction effect withstood adjustment for multiple comparisons. There were no statistically significant interactions between immune response genotypes and IM on other NHL subtypes. CONCLUSIONS: Genetic risk variants in IL1B and IL6 may affect the association between IM and TCL, possibly by influencing T-cell activation, growth, and differentiation in the presence of IM, thereby decreasing risk of immune cell proliferation.


Assuntos
Mononucleose Infecciosa/genética , Linfoma não Hodgkin/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Teorema de Bayes , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Mononucleose Infecciosa/imunologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Autorrelato , Adulto Jovem
20.
Cancer Epidemiol Biomarkers Prev ; 29(5): 936-941, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32066614

RESUMO

BACKGROUND: We assessed the ability to supplement existing epidemiologic/etiologic studies with data on treatment and clinical outcomes by linking to publicly available cancer registry and administrative databases. METHODS: Medical records were retrieved and abstracted for cases enrolled in a Los Angeles County case-control study of non-Hodgkin lymphoma (NHL). Cases were linked to the Los Angeles County cancer registry (CSP), the California state hospitalization discharge database (OSHPD), and the SEER-Medicare database. We assessed sensitivity, specificity, and positive predictive value (PPV) of cancer treatment in linked databases, compared with medical record abstraction. RESULTS: We successfully retrieved medical records for 918 of 1,004 participating NHL cases and abstracted treatment for 698. We linked 59% of cases (96% of cases >65 years old) to SEER-Medicare and 96% to OSHPD. Chemotherapy was the most common treatment and best captured, with the highest sensitivity in SEER-Medicare (80%) and CSP (74%); combining all three data sources together increased sensitivity (92%), at reduced specificity (56%). Sensitivity for radiotherapy was moderate: 77% with aggregated data. Sensitivity of BMT was low in the CSP (42%), but high for the administrative databases, especially OSHPD (98%). Sensitivity for surgery reached 83% when considering all three datasets in aggregate, but PPV was 60%. In general, sensitivity and PPV for chronic lymphocytic leukemia/small lymphocytic lymphoma were low. CONCLUSIONS: Chemotherapy was accurately captured by all data sources. Hospitalization data yielded the highest performance values for BMTs. Performance measures for radiotherapy and surgery were moderate. IMPACT: Various administrative databases can supplement epidemiologic studies, depending on treatment type and NHL subtype of interest.


Assuntos
Mineração de Dados/métodos , Registros Eletrônicos de Saúde/estatística & dados numéricos , Linfoma não Hodgkin/terapia , Medicare/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Demandas Administrativas em Assistência à Saúde/estatística & dados numéricos , Adulto , Idoso , Estudos de Casos e Controles , Tratamento Farmacológico/estatística & dados numéricos , Feminino , Humanos , Incidência , Los Angeles/epidemiologia , Linfoma não Hodgkin/epidemiologia , Pessoa de Meia-Idade , Radioterapia/estatística & dados numéricos , Programa de SEER/estatística & dados numéricos , Sensibilidade e Especificidade , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Estados Unidos , Adulto Jovem
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