Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 137
Filtrar
1.
Nat Commun ; 12(1): 970, 2021 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579919

RESUMO

Even distinct cancer types share biological hallmarks. Here, we investigate polygenic risk score (PRS)-specific pleiotropy across 16 cancers in European ancestry individuals from the Genetic Epidemiology Research on Adult Health and Aging cohort (16,012 cases, 50,552 controls) and UK Biobank (48,969 cases, 359,802 controls). Within cohorts, each PRS is evaluated in multivariable logistic regression models against all other cancer types. Results are then meta-analyzed across cohorts. Ten positive and one inverse cross-cancer associations are found after multiple testing correction. Two pairs show bidirectional associations; the melanoma PRS is positively associated with oral cavity/pharyngeal cancer and vice versa, whereas the lung cancer PRS is positively associated with oral cavity/pharyngeal cancer, and the oral cavity/pharyngeal cancer PRS is inversely associated with lung cancer. Overall, we validate known, and uncover previously unreported, patterns of pleiotropy that have the potential to inform investigations of risk prediction, shared etiology, and precision cancer prevention strategies.


Assuntos
Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/genética , Epidemiologia Molecular , Adulto , Idoso , Biomarcadores Tumorais/genética , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
2.
Cancer ; 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33620753

RESUMO

BACKGROUND: It has been shown that racial/ethnic disparities exist with regard to initiation of and adherence to adjuvant endocrine therapy (AET). However, the relationship among American Indian/Alaska Native (AIAN) individuals is poorly understood, particularly among those who reside in urban areas. We evaluated whether AET initiation and adherence were lower among AIAN individuals than those of other races/ethnicities who were enrolled in the Kaiser Permanente of Northern California (KPNC) health system. METHODS: We identified 23,680 patients from the period 1997 to 2014 who were eligible for AET (first primary, stage I-III, hormone receptor-positive breast cancer) and used KPNC pharmacy records to identify AET prescriptions and refill dates. We assessed AET initiation (≥1 filled prescription within 1 year of diagnosis) and AET adherence (proportion of days covered ≥80%) every year up to 5 years after AET initiation. RESULTS: At the end of the 5-year follow-up period, 83% of patients were AET initiators, and 58% were AET adherent. Compared with other races/ethnicities, AIAN women had the second-lowest rate of AET initiation (non-Hispanic Black [NHB], 78.0%; AIAN, 78.6%; Hispanic, 83.0%; non-Hispanic White [NHW], 82.5%; Asian/Pacific Islander [API], 84.7%), the lowest rate of AET adherence after 1 year and 5 years of follow-up (70.3% and 50.8%, respectively), and the greatest annual decline in AET adherence during the 4- to 5-year period of follow-up (a 13.8% decrease in AET adherence [from 64.6% to 50.8%]) after initiation of AET. In adjusted multivariable models, AIAN, Hispanic, and NHB women were less likely than NHW women to be AET adherent. At the end of the 5-year period, total underutilization (combining initiation and adherence) in AET-eligible patients was greatest among AIAN (70.6%) patients, followed by NHB (69.6%), Hispanic (63.2%), NHW (58.7%), and API (52.3%) patients, underscoring the AET treatment gap. CONCLUSION: Our results suggest that AET initiation and adherence are particularly low for insured AIAN women.

3.
Cancer Res ; 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33293427

RESUMO

To identify rare variants associated with prostate cancer (PrCa) susceptibility and better characterize the mechanisms and cumulative disease risk associated with common risk variants, we conducted an integrated study of PrCa genetic etiology in two cohorts using custom genotyping microarrays, large imputation reference panels, and functional annotation approaches. Specifically, 11,984 men (6,196 PrCa cases, 5,788 controls) of European ancestry from Northern California Kaiser Permanente were genotyped and meta-analyzed with 196,269 men of European ancestry (7,917 PrCa cases, 188,352 controls) from the UK Biobank. Three novel loci, including two rare variants (European ancestry minor allele frequency < 0.01, at 3p21.31 and 8p12), were significant genome-wide in a meta-analysis. Gene-based rare variant tests implicated a known PrCa gene (HOXB13), as well as a novel candidate gene (ILDR1), which encodes a receptor highly expressed in prostate tissue and is related to the B7/CD28 family of T cell immune checkpoint markers. Haplotypic patterns of long-range linkage disequilibrium were observed for rare genetic variants at HOXB13 and other loci, reflecting their evolutionary history. Additionally, a polygenic risk score (PRS) of 188 PrCa variants was strongly associated with risk (90th vs. 40-60th percentile OR = 2.62, P = 2.55*10-191). Many of the 188 variants exhibited functional signatures of gene expression regulation or transcription factor binding, including a six-fold difference in log-probability of Androgen Receptor binding at the variant rs2680708 (17q22). Rare variant and PRS associations, with concomitant functional interpretation of risk mechanisms can help clarify the full genetic architecture of PrCa and other complex traits.

4.
Nat Commun ; 11(1): 5116, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037222

RESUMO

Mammographic density (MD) phenotypes are strongly associated with breast cancer risk and highly heritable. In this GWAS meta-analysis of 24,192 women, we identify 31 MD loci at P < 5 × 10-8, tripling the number known to 46. Seventeen identified MD loci also are associated with breast cancer risk in an independent meta-analysis (P < 0.05). Mendelian randomization analyses show that genetic estimates of dense area (DA), nondense area (NDA), and percent density (PD) are all significantly associated with breast cancer risk (P < 0.05). Pathway analyses reveal distinct biological processes involving DA, NDA and PD loci. These findings provide additional insights into the genetic basis of MD phenotypes and their associations with breast cancer risk.


Assuntos
Densidade da Mama , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , Predisposição Genética para Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Estudo de Associação Genômica Ampla , Humanos , Mamografia , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
5.
Nat Commun ; 11(1): 4423, 2020 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-32887889

RESUMO

Deciphering the shared genetic basis of distinct cancers has the potential to elucidate carcinogenic mechanisms and inform broadly applicable risk assessment efforts. Here, we undertake genome-wide association studies (GWAS) and comprehensive evaluations of heritability and pleiotropy across 18 cancer types in two large, population-based cohorts: the UK Biobank (408,786 European ancestry individuals; 48,961 cancer cases) and the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging cohorts (66,526 European ancestry individuals; 16,001 cancer cases). The GWAS detect 21 genome-wide significant associations independent of previously reported results. Investigations of pleiotropy identify 12 cancer pairs exhibiting either positive or negative genetic correlations; 25 pleiotropic loci; and 100 independent pleiotropic variants, many of which are regulatory elements and/or influence cross-tissue gene expression. Our findings demonstrate widespread pleiotropy and offer further insight into the complex genetic architecture of cross-cancer susceptibility.


Assuntos
Carcinogênese/genética , Neoplasias/genética , Adulto , Idoso , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Pleiotropia Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Polimorfismo de Nucleotídeo Único , Medição de Risco , Fatores de Risco
6.
Epidemiology ; 31(6): 860-871, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32897909

RESUMO

BACKGROUND: We examined whether the apparent association between renal cell carcinoma (RCC) and use of dihydropyridine calcium channel blockers (CCBs) was explained by confounding by indication since hypertension, the main indication for CCBs, is a risk factor for RCC. METHODS: Using Danish health registries, we conducted a nested case-control study including 7315 RCC cases during 2000-2015. We matched each case with up to 20 controls on age and sex using risk-set sampling. We estimated odds ratios (ORs) for long-term CCB use associated with RCC using conditional logistic regression. We addressed confounding by indication by (1) adjusting for hypertension severity indicators; (2) evaluating dose-response patterns; (3) examining whether other first-line anti-hypertensives were associated with RCC; and (4) using an active comparator new user design by nesting the study in new users of CCBs or angiotensin-converting enzyme inhibitors (ACEIs). RESULTS: The adjusted OR for RCC associated with long-term CCB use compared to non-use was 1.76 (1.63-1.90). After we additionally adjusted for hypertension severity indicators, the OR remained elevated (OR 1.37; confidence interval [CI] 1.25, 1.49) with evidence of a dose-response pattern. Other anti-hypertensives were also associated with RCC, for example, ACEIs (OR 1.27; 95% CI = 1.16, 1.39) and thiazides (OR 1.22; 95% CI = 1.12, 1.34). In the active comparator new user design, the OR was 1.21 (95% CI = 0.95, 1.53) for use of CCBs compared with ACEIs. CONCLUSIONS: In this population, confounding by indication appeared to explain at least part of the association between RCC and dihydropyridine CCBs.

7.
Oncologist ; 25(8): 712-721, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32250503

RESUMO

BACKGROUND: Recent clinical trials have evaluated angiotensin-converting enzyme (ACE) inhibitors (ACEis), angiotensin receptor blockers (ARBs), and beta blockers (BBs) in relation to cardiotoxicity in patients with cancer, typically defined by ejection fraction declines. However, these trials have not examined long-term, hard clinical endpoints. Within a prospective study, we examined the risk of heart failure (HF) and coronary heart disease (CHD) events in relation to use of commonly used antihypertensive medications, including ACEis/ARBs, BBs, calcium channel blockers (CCB), and diuretics, comparing women with and without cancer. MATERIALS AND METHODS: In a cohort of 56,997 Women's Health Initiative study participants free of cardiovascular disease who received antihypertensive treatment, we used multivariable-adjusted Cox regression models to calculate the hazard ratios (HRs) of developing CHD, HF, and a composite outcome of cardiac events (combining CHD and HF) in relation to use of ACEis/ARBs, CCBs, or diuretics versus BBs, separately in women with and without cancer. RESULTS: Whereas there was no difference in risk of cardiac events comparing ACEi/ARB with BB use among cancer-free women (HR = 0.99 [0.88-1.12]), among cancer survivors ACEi/ARB users were at a 2.24-fold risk of total cardiac events (1.18-4.24); p-interaction = .06). When investigated in relation to CHD only, an increased risk was similarly observed in ACEi/ARB versus BB use for cancer survivors (HR = 1.87 [0.88-3.95]) but not in cancer-free women (HR = 0.91 [0.79-1.06]; p-interaction = .04). A similar pattern was also seen in relation to HF but did not reach statistical significance (p-interaction = .23). CONCLUSION: These results from this observational study suggest differing risks of cardiac events in relation to antihypertensive medications depending on history of cancer. Although these results require replication before becoming actionable in a clinical setting, they suggest the need for more rigorous examination of the effect of antihypertensive choice on long-term cardiac outcomes in cancer survivors. IMPLICATIONS FOR PRACTICE: Although additional research is needed to replicate these findings, these data from a large, nationally representative sample of postmenopausal women indicate that beta blockers are favorable to angiotensin-converting enzyme inhibitors in reducing the risk of cardiac events among cancer survivors. This differs from the patterns observed in a noncancer cohort, which largely mirrors what is found in the randomized clinical trials in the general population.

8.
Cancer Epidemiol Biomarkers Prev ; 29(5): 1039-1048, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32066618

RESUMO

BACKGROUND: Percent density (PD) is a strong risk factor for breast cancer that is potentially modifiable by lifestyle factors. PD is a composite of the dense (DA) and nondense (NDA) areas of a mammogram, representing predominantly fibroglandular or fatty tissues, respectively. Alcohol and tobacco use have been associated with increased breast cancer risk. However, their effects on mammographic density (MD) phenotypes are poorly understood. METHODS: We examined associations of alcohol and tobacco use with PD, DA, and NDA in a population-based cohort of 23,456 women screened using full-field digital mammography machines manufactured by Hologic or General Electric. MD was measured using Cumulus. Machine-specific effects were estimated using linear regression, and combined using random effects meta-analysis. RESULTS: Alcohol use was positively associated with PD (P trend = 0.01), unassociated with DA (P trend = 0.23), and inversely associated with NDA (P trend = 0.02) adjusting for age, body mass index, reproductive factors, physical activity, and family history of breast cancer. In contrast, tobacco use was inversely associated with PD (P trend = 0.0008), unassociated with DA (P trend = 0.93), and positively associated with NDA (P trend<0.0001). These trends were stronger in normal and overweight women than in obese women. CONCLUSIONS: These findings suggest that associations of alcohol and tobacco use with PD result more from their associations with NDA than DA. IMPACT: PD and NDA may mediate the association of alcohol drinking, but not tobacco smoking, with increased breast cancer risk. Further studies are needed to elucidate the modifiable lifestyle factors that influence breast tissue composition, and the important role of the fatty tissues on breast health.

9.
Breast Cancer Res Treat ; 180(1): 219-226, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31975315

RESUMO

PURPOSE: Reports suggest that up to 50% of women with hormone receptor-positive (HR+) breast cancer (BC) do not complete the recommended 5 years of adjuvant endocrine therapy (AET). We examined the impact of an outreach program at Kaiser Permanente Northern California (KPNC) on adherence and discontinuation of AET among patients who initiated AET. METHODS: We assembled a retrospective cohort of all KPNC patients diagnosed with HR+, stage I-III BC initiating AET before (n = 4287) and after (n = 3580) implementation of the outreach program. We compared adherence proportions and discontinuation rates before and after program implementation, both crude and adjusted for age, race/ethnicity, education, income, and stage. We conducted a pooled analysis of data from six Cancer Research Network (CRN) sites that had not implemented programs for improving AET adherence, using identical methods and time periods, to assess possible secular trends. RESULTS: In the pre-outreach period, estimated adherence in years 1, 2, and 3 following AET initiation was 75.2%, 71.0%, and 67.3%; following the outreach program, the estimates were 79.4%, 75.6%, and 72.2% (p-values < .0001 for pairwise comparisons). Results were comparable after adjusting for clinical and demographic factors. The estimated cumulative incidence of discontinuation was 0.22 (0.21-0.24) and 0.18 (0.17-0.19) at 3 years for pre- and post-outreach groups (p-value < .0001). We found no evidence of an increase in adherence between the study periods at the CRN sites with no AET adherence program. CONCLUSION: Adherence and discontinuation after AET initiation improved modestly following implementation of the outreach program.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/etiologia , Neoplasias da Mama/patologia , California/epidemiologia , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Implementação de Plano de Saúde , Humanos , Adesão à Medicação , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Melhoria de Qualidade , Programas Médicos Regionais , Sistema de Registros , Estudos Retrospectivos , Fatores Socioeconômicos
10.
Perm J ; 242020.
Artigo em Inglês | MEDLINE | ID: mdl-31852040

RESUMO

CONTEXT: The antipsychotic drug haloperidol has antiproliferative and growth-inhibiting properties on prostate cancer cell lines in vitro by binding the sigma 1 protein. Evidence is needed regarding a possible preventive association in men. OBJECTIVE: To examine whether our epidemiologic data support an inverse association of haloperidol use with risk of prostate cancer. DESIGN: These case-control analyses used conditional logistic regression to estimate relative risk by odds ratios (ORs) adjusting for race/ethnicity and aspects of medical care related to detection of prostate cancer. We tested 3 other commonly used antipsychotic drugs, risperidone, quetiapine, and olanzapine, for sigma 1 protein binding and inhibition of clonogenic growth of prostate cancer cells. Use of any of these by men was considered use of a comparator drug. MAIN OUTCOME MEASURES: 1) association of haloperidol with prostate cancer; 2) sigma 1 binding and clonogenic growth. RESULTS: Probably owing to small numbers of haloperidol recipients, evidence of a preventive association was inconsistent, depending on the definition of long-term use. If duration of use was greater than 1 year, the odds ratio (OR) was 0.38 (95% confidence interval (CI) = 0.14-1.01) for haloperidol and 0.80 (95% CI = 0.66-0.98) for the comparator drug; if the duration of use was greater than 2 years, the OR was 0.66 (95% CI = 0.24-1.76) for haloperidol and 0.84 (95% CI = 0.66-1.08) for the comparator drug. Unlike haloperidol, risperidone, quetiapine, and olanzapine did not bind sigma 1 or inhibit clonogenic growth. CONCLUSION: Given the laboratory evidence, our ambiguous epidemiologic findings should encourage more epidemiologic evaluation of haloperidol use and risk of prostate cancer. Finding a negative association could be a scientific advance in prostate cancer prevention but would not be sufficient basis for recommending the prescription of haloperidol for that purpose.

12.
Arch Osteoporos ; 14(1): 73, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31254147

RESUMO

We examined the fracture risk after initiation of blood pressure-lowering drugs compared with initiation of antidepressants. Multivariable regression models demonstrated an increased risk of fracture among women initiating a blood pressure-lowering medication (HR 1.73, 95% CI 1.02-2.95). This is likely related to an increased risk of falls. PURPOSE: Initiation of blood pressure-lowering drugs has been associated with fractures in several studies, presumably due to an increase in the risk of falls. However, these studies used self-controlled designs without active comparators. We examined the risk of fractures after initiation of blood pressure lowering drugs compared with initiation of antidepressants. METHODS: Women participants in the Study of Women Across the Nation (SWAN) were potentially eligible if they initiated blood pressure-lowering or antidepressant drugs during follow-up. To reduce the risk of confounding, we estimated a propensity score that included potential confounders including age, menopausal status, osteoporosis, and osteoporosis medication use. The propensity score was used to match subjects in both groups and we then constructed multivariable logistic regression models comparing the risk of any fracture. Sensitivity analyses assessed a limited range of fractures less likely related to trauma. RESULTS: Among the 3302 potentially eligible women participating in the SWAN cohort, we were able to propensity-score match 289 women who initiated a blood pressure-lowering medication with 289 who initiated an antidepressant. Multivariable logistic regression models demonstrated an increased risk of fracture among women initiating a blood pressure lowering medication (OR 1.74, 95% CI 1.02-2.95). After excluding fractures of the digits and face, the results were similar (OR 1.57, 95% CI 0.88-2.81). CONCLUSIONS: There was evidence of an increased risk in fractures among women initiating blood pressure-lowering medications compared to those initiating antidepressants. This is likely related to an increased risk of falling.


Assuntos
Antidepressivos/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Fraturas Ósseas/epidemiologia , Acidentes por Quedas , Pressão Sanguínea , Estudos de Coortes , Feminino , Fraturas Ósseas/etiologia , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Osteoporose/complicações , Farmacoepidemiologia , Pontuação de Propensão , Medição de Risco , Fatores de Risco , Estados Unidos/epidemiologia
13.
Perm J ; 232019.
Artigo em Inglês | MEDLINE | ID: mdl-30939265

RESUMO

CONTEXT: Epidemiologic analyses of gabapentin use and cancer risk in Kaiser Permanente Northern California were previously carried out in a collaborative study and independently evaluated in a UK database. OBJECTIVE: To update these epidemiologic analyses with 7.5 more years of follow-up. DESIGN: Case-control analyses using conditional logistic regression to estimate relative risk by odds ratios using the prior collaboration's criteria for identifying positive drug-cancer associations and our more stringent criteria requiring stronger association, lower p values, and evidence of dose response. New associations were reanalyzed with additional control for limited measures of smoking and alcohol use. MAIN OUTCOME MEASURES: Gabapentin-cancer associations. RESULTS: No previously found associations met our stringent criteria, but cancers of the mouth/pharynx, esophagus, liver, and vagina did. All odds ratios for 3 or more and 8 or more prescriptions were moderately reduced by control for smoking and alcohol. Substantial elevations of risk of mouth/pharynx, liver, and vaginal cancers were associated with only 1 prescription dispensed. Sensitivity analyses aimed at possible confounding and other biases did not change our conclusions but did reveal a markedly increased risk of vaginal cancer in gabapentin users with epilepsy compared with users without. CONCLUSION: The reduced magnitude of relative risk with control for smoking and alcohol use suggests confounding by known risk factors. Biologically implausible elevated risk from just 1 prescription suggests confounding by indication. Either or both of these concerns applies to each of the 4 cancer sites associated with gabapentin use. Updated analyses show little if any evidence for carcinogenic effects of gabapentin.


Assuntos
Analgésicos/administração & dosagem , Gabapentina/administração & dosagem , Neoplasias/epidemiologia , California/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Masculino , Medição de Risco , Sensibilidade e Especificidade , Reino Unido/epidemiologia
14.
Int J Cancer ; 145(12): 3244-3256, 2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30873591

RESUMO

Insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross-sectional associations of these exposures with circulating concentrations of IGFs (IGF-I and IGF-II) and IGFBPs (IGFBP-1, IGFBP-2 and IGFBP-3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22-89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGF-I, IGF-II and IGFBP-3. Higher body mass index was associated with lower concentrations of IGFBP-1 and IGFBP-2. Taller height was associated with higher concentrations of IGF-I and IGFBP-3 and lower concentrations of IGFBP-1. Smokers had higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGFBP-3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF-II and lower concentrations of IGF-I and IGFBP-2. African Americans had lower concentrations of IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 and Hispanics had lower IGF-I, IGF-II and IGFBP-3 than non-Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.


Assuntos
Biomarcadores Tumorais/sangue , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Fator de Crescimento Insulin-Like II/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Neoplasias/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antropometria/métodos , Biomarcadores Tumorais/metabolismo , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , Neoplasias/metabolismo , Estudos Prospectivos , Adulto Jovem
15.
Am J Epidemiol ; 188(6): 1144-1154, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30865217

RESUMO

Breast density is a modifiable factor that is strongly associated with breast cancer risk. We sought to understand the influence of newer technologies of full-field digital mammography (FFDM) on breast density research and to determine whether results are comparable across studies using FFDM and previous studies using traditional film-screen mammography. We studied 24,840 screening-age (40-74 years) non-Hispanic white women who were participants in the Research Program on Genes, Environment and Health of Kaiser Permanente Northern California and underwent screening mammography with either Hologic (Hologic, Inc., Marlborough, Massachusetts) or General Electric (General Electric Company, Boston, Massachusetts) FFDM machines between 2003 and 2013. We estimated the associations of parity, age at first birth, age at menarche, and menopausal status with percent density and dense area as measured by a single radiological technologist using Cumulus software (Canto Software, Inc., San Francisco, California). We found that associations between reproductive factors and mammographic density measured using processed FFDM images were generally similar in magnitude and direction to those from prior studies using film mammography. Estimated associations for both types of FFDM machines were in the same direction. There was some evidence of heterogeneity in the magnitude of the effect sizes by machine type, which we accounted for using random-effects meta-analysis when combining results. Our findings demonstrate the robustness of quantitative mammographic density measurements across FFDM and film mammography platforms.


Assuntos
Densidade da Mama/fisiologia , Neoplasias da Mama/epidemiologia , Mamografia/métodos , História Reprodutiva , Adulto , Idoso , Neoplasias da Mama/diagnóstico por imagem , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Menarca/fisiologia , Menopausa/fisiologia , Pessoa de Meia-Idade , Paridade
16.
Lung Cancer ; 125: 51-56, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30429038

RESUMO

OBJECTIVES: To examine the role of uniform access to care in reducing racial/ethnic disparities in receipt of resection for early stage non-small cell lung cancer (NSCLC) by comparing integrated health system member patients to demographically similar non-member patients. MATERIALS AND METHODS: Using data from the California Cancer Registry, we conducted a retrospective cohort study of patients from four racial/ethnic groups (White, Black, Hispanic, Asian/Pacific Islander), aged 21-80, with a first primary diagnosis of stage I or II NSCLC between 2004 and 2011, in counties served by Kaiser Permanente Northern California (KPNC) at diagnosis. Our cohort included 1565 KPNC member and 4221 non-member patients. To examine the relationship between race/ethnicity and receipt of surgery stratified by KPNC membership, we used modified Poisson regression to calculate risk ratios (RR) adjusted for patient demographic and tumor characteristics. RESULTS: Black patients were least likely to receive surgery regardless of access to integrated care (64-65% in both groups). The magnitude of the black-white difference in the likelihood of surgery receipt was similar for members (RR: 0.82, 95% CI: 0.73-0.93) and non-members (RR: 0.86, 95% CI: 0.80-0.94). Among members, roughly equal proportions of Hispanic and White patients received surgery; however, among non-members, Hispanic patients were less likely to receive surgery (non-members, RR: 0.93, 95% CI: 0.86-1.00; members, RR: 0.98, 95% CI: 0.89-1.08). CONCLUSION: Disparities in surgical treatment for NSCLC were not reduced through integrated health system membership, suggesting that factors other than access to care (e.g., patient-provider communication) may underlie disparities. Future research should focus on identifying such modifiable factors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Acesso aos Serviços de Saúde/ética , Disparidades em Assistência à Saúde/ética , Neoplasias Pulmonares/cirurgia , Grupos Populacionais/ética , Adulto , Idoso , Idoso de 80 Anos ou mais , California , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
17.
J Cancer Surviv ; 12(6): 794-802, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30338462

RESUMO

PURPOSE: To investigate the implications of a cancer diagnosis on medication adherence for pre-existing comorbid conditions, we explored statin adherence patterns prior to and following a new diagnosis of breast, colorectal, or prostate cancer among a multi-ethnic cohort. METHODS: We identified adults enrolled at Kaiser Permanente Northern California who were prevalent statin medication users, newly diagnosed with breast, colorectal, or prostate cancer between 2000 and 2012. Statin adherence was measured using the proportion of days covered (PDC) during the 2-year pre-cancer diagnosis and the 2-year post-cancer diagnosis. Adherence patterns were assessed using generalized estimating equations, for all cancers combined and stratified by cancer type and race/ethnicity, adjusted for demographic, clinical, and tumor characteristics. RESULTS: Among 10,177 cancer patients, statin adherence decreased from pre- to post-cancer diagnosis (adjusted odds ratio (ORadj):0.91, 95% confidence interval (95% CI):0.88-0.94). Statin adherence decreased from pre- to post-cancer diagnosis among breast (ORadj:0.94, 95% CI:0.90-0.99) and colorectal (ORadj:0.79, 95% CI:0.74-0.85) cancer patients. No difference in adherence was observed among prostate cancer patients (ORadj:1.01, 95% CI:0.97-1.05). Prior to cancer diagnosis, adherence to statins was generally higher among non-Hispanic whites and multi-race patients than other groups. However, statin adherence after diagnosis decreased only among these two populations (ORadj:0.85, 95% CI:0.85-0.92 and ORadj:0.86, 95% CI:0.76-0.97), respectively. CONCLUSIONS: We found substantial variation in statin medication adherence following diagnosis by cancer type and race/ethnicity among a large cohort of prevalent statin users in an integrated health care setting. IMPLICATIONS FOR CANCER SURVIVORS: Improving our understanding of comorbidity management and polypharmacy across diverse cancer patient populations is warranted to develop tailored interventions that improve medication adherence and reduce disparities in health outcomes.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias Colorretais/epidemiologia , Grupos Étnicos/estatística & dados numéricos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/epidemiologia , Adesão à Medicação , Neoplasias da Próstata/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/etnologia , California/epidemiologia , Estudos de Coortes , Neoplasias Colorretais/complicações , Neoplasias Colorretais/etnologia , Grupos de Populações Continentais/estatística & dados numéricos , Feminino , Humanos , Hipercolesterolemia/complicações , Masculino , Adesão à Medicação/etnologia , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Prevalência , Neoplasias da Próstata/complicações , Neoplasias da Próstata/etnologia
18.
Cancer Epidemiol Biomarkers Prev ; 27(5): 525-530, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29716927

RESUMO

Background: Several epidemiologic studies have reported strong inverse associations between metformin use and risk of colorectal cancer, although time-related biases, such as immortal time bias, may in part explain these findings. We reexamined this association using methods to minimize these biases.Methods: A cohort study was conducted among 47,351 members of Kaiser Permanente Northern California with diabetes and no history of cancer or metformin use. Follow-up for incident colorectal cancer occurred from January 1, 1997, until June 30, 2012. Cox regression was used to calculate HRs and 95% confidence intervals (CIs) for colorectal cancer risk associated with metformin use (ever use, total duration, recency of use, and cumulative dose).Results: No association was observed between ever use of metformin and colorectal cancer risk (HR, 0.90; 95% CI, 0.76-1.07) and there was no consistent pattern of decreasing risk with increasing total duration, dose, or recency of use. However, long-term use (≥5.0 years) appeared to be associated with reduced risk of colorectal cancer in the full population (HR, 0.78; 95% CI, 0.60-1.02), among current users (HR, 0.78; 95% CI, 0.59-1.04), and in men (HR, 0.65; 95% CI, 0.45-0.94) but not in women. Higher cumulative doses of metformin were associated with reduced risk. In initial users of sulfonylureas, switching to or adding metformin was also associated with decreased colorectal cancer risk.Conclusions: Our findings showed an inverse association between long-term use of metformin and colorectal cancer risk. Findings, especially the risk reduction among men, need to be confirmed in large, well-conducted studies.Impact: If our findings are confirmed, metformin may have a role in the chemoprevention of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 27(5); 525-30. ©2018 AACRSee related commentary by Jackson and García-Albéniz, p. 520.


Assuntos
Neoplasias Colorretais/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Adulto , Idoso , Viés , California/epidemiologia , Neoplasias Colorretais/prevenção & controle , Interpretação Estatística de Dados , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
19.
Cancer Causes Control ; 29(3): 305-314, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29427260

RESUMO

PURPOSE: The purpose of the study was to assess the feasibility of quantifying long-term trends in breast tumor DNA copy number variation (CNV) profiles. METHODS: We evaluated CNV profiles in formalin-fixed paraffin-embedded (FFPE) tumor specimens from 30 randomly selected Kaiser Permanente Northern California health plan women members diagnosed with breast cancer from 1950 to 2010. Assays were conducted for five cases per decade who had available tumor blocks and pathology reports. RESULTS: As compared to the tumors from the 1970s to 2000s, the older tumors dating back to the 1950s and 1960s were much more likely to (1) fail quality control, and (2) have fewer CNV events (average 23 and 31 vs. 58 to 69), fewer CNV genes (average 5.1 and 3.7k vs. 8.1 to 10.3k), shorter CNV length (average 2,440 and 3,300k vs. 5,740 to 9,280k), fewer high frequency Del genes (37 and 25% vs. 54 to 76%), and fewer high frequency high_Amp genes (20% vs. 56 to 73%). On average, assay interpretation took an extra 60 min/specimen for cases from the 1960s versus 20 min/specimen for the most recent tumors. CONCLUSIONS: Assays conducted in the mid-2010s for CNVs may be feasible for FFPE tumor specimens dating back to the 1980s, but less feasible for older specimens.


Assuntos
Neoplasias da Mama/genética , Variações do Número de Cópias de DNA , DNA , Manejo de Espécimes , Feminino , Formaldeído , Humanos , Inclusão em Parafina , Fatores de Tempo , Fixação de Tecidos
20.
Breast Cancer Res Treat ; 167(3): 751-759, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29079937

RESUMO

PURPOSE: A majority of women with ductal carcinoma in situ (DCIS) receive breast-conserving surgery (BCS) but then face a risk of ipsilateral breast tumor recurrence (IBTR) which can be either recurrence of DCIS or invasive breast cancer. We developed a score to provide individualized information about IBTR risk to guide treatment decisions. METHODS: Data from 2762 patients treated with BCS for DCIS at centers within the National Comprehensive Cancer Network (NCCN) were used to identify statistically significant non-treatment-related predictors for 5-year IBTR. Factors most associated with IBTR were estrogen-receptor status of the DCIS, presence of comedo necrosis, and patient age at diagnosis. These three parameters were used to create a point-based risk score. Discrimination of this score was assessed in a separate DCIS population of 301 women (100 with IBTR and 200 without) from Kaiser Permanente Northern California (KPNC). RESULTS: Using NCCN data, the 5-year likelihood of IBTR without adjuvant therapy was 9% (95% CI 5-12%), 23% (95% CI 13-32%), and 51% (95% CI 26-75%) in the low, intermediate, and high-risk groups, respectively. Addition of the risk score to a model including only treatment improved the C-statistic from 0.69 to 0.74 (improvement of 0.05). Cross-validation of the score resulted in a C-statistic of 0.76. The score had a c-statistic of 0.67 using the KPNC data, revealing that it discriminated well. CONCLUSIONS: This simple, no-cost risk score may be used by patients and physicians to facilitate preference-based decision-making about DCIS management informed by a more accurate understanding of risks.


Assuntos
Neoplasias da Mama/epidemiologia , Carcinoma Intraductal não Infiltrante/epidemiologia , Mastectomia Segmentar , Recidiva Local de Neoplasia/epidemiologia , Adulto , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/radioterapia , Carcinoma Intraductal não Infiltrante/cirurgia , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Radioterapia Adjuvante , Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...