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1.
J Natl Cancer Inst ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33010161

RESUMO

BACKGROUND: In the era of widespread prostate-specific antigen testing, it is important to focus etiologic research on the outcome of aggressive prostate cancer, but studies have defined this outcome differently. We aimed to develop an evidence-based consensus definition of aggressive prostate cancer using clinical features at diagnosis for etiologic epidemiologic research. METHODS: Among prostate cancer cases diagnosed in 2007 in the U.S. SEER-18 database with follow-up through 2017, we compared the performance of categorizations of aggressive prostate cancer in discriminating fatal prostate cancer within 10 years of diagnosis, placing the most emphasis on sensitivity and positive predictive value (PPV). RESULTS: In our case population (n = 55,900), 3,073 men died of prostate cancer within 10 years. Among 12 definitions that included TNM stage and Gleason score, sensitivities ranged from 0.64 to 0.89 and PPVs ranged from 0.09 to 0.23. We propose defining aggressive prostate cancer as diagnosis of stage T4 or N1 or M1 or Gleason score ≥8 prostate cancer, as this definition had one of the higher PPVs (0.23, 95% confidence interval [CI] 0.22-0.24) and reasonable sensitivity (0.66, 95% CI 0.64-0.67) for prostate cancer death within 10 years. Results were similar across sensitivity analyses. CONCLUSIONS: We recommend that etiologic epidemiologic studies of prostate cancer report results for this definition of aggressive prostate cancer. We also recommend that studies separately report results for advanced stage (T4 or N1 or M1), high grade (Gleason score ≥8), and fatal prostate cancer. Use of this comprehensive set of endpoints will facilitate comparison of results from different studies and help elucidate prostate cancer etiology.

2.
Sleep ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33015707

RESUMO

BACKGROUND: Chronic intermittent hypoxia resulting from obstructive sleep apnea (OSA) may activate multiple carcinogenic pathways and lead to cancer development. METHODS: We prospectively examined the association between OSA and cancer risk among 65,330 women in the Nurses' Health Study who were free of cancer in 2008 (mean age: 73.3 years). Incident cancer diagnoses were collected until 2016 and confirmed by pathology reports. Clinically-diagnosed OSA was self-reported in 2008 and updated in 2012. We used time-dependent Cox regression to estimate hazard ratios (HR) for the associations of OSA with total and site-specific cancer risk. RESULTS: We documented 5,257 incident cancer diagnoses during follow-up. In the age-adjusted model, OSA was associated with a 15% (95% CI: 1.03, 1.29) increase in total cancer risk. The association became non-significant after adjustment for multiple cancer risk factors (HR: 1.08; 95% CI: 0.96, 1.21). When examining cancer risk by site, OSA was associated with significantly increased risk for lung (fully-adjusted HR: 1.52; 95% CI: 1.07, 2.17), bladder (fully-adjusted HR: 1.94; 95% CI: 1.12, 3.35) and thyroid cancer (fully-adjusted HR: 2.06; 95% CI: 1.01, 4.22) and possibly increased risk for kidney cancer (fully-adjusted HR: 1.59; 95% CI: 0.84, 3.01). When grouping cancer sites by risk factor profiles, OSA was positively associated with smoking-related cancers (fully-adjusted HR: 1.37; 95% CI: 1.11, 1.67), and this association was stronger in never smokers than ever smokers. CONCLUSION: While OSA was not independently associated with overall cancer risk in older women, significant associations were observed for smoking-related cancers, especially in non-smokers.

3.
BMJ ; 370: m2942, 2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32878860

RESUMO

OBJECTIVE: To evaluate the associations between personal use of permanent hair dyes and cancer risk and mortality. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: 117 200 women enrolled in the Nurses' Health Study, an ongoing prospective cohort study of female nurses in the United States. The women were free of cancer at baseline, reported information on personal use of permanent hair dyes, and were followed for 36 years. EXPOSURE: Status, duration, frequency, and integral use (cumulative dose calculated from duration and frequency) of permanent hair dyes. Age at first use and time since first use of permanent hair dyes. MAIN OUTCOME MEASURES: Associations of personal use of permanent hair dyes with risk of overall cancer and specific cancers, and cancer related death. Age and multivariable adjusted hazard ratios and 95% confidence intervals were estimated by using Cox proportional hazard models. RESULTS: Ever users of permanent hair dyes had no significant increases in risk of solid cancers (n=20 805, excluding non-melanoma skin cancers; hazard ratio 0.98, 95% confidence interval 0.96 to 1.01) or hematopoietic cancers overall (n=1807; 1.00, 0.91 to 1.10) compared with non-users. Additionally, ever users did not have an increased risk of most specific cancers (cutaneous squamous cell carcinoma, bladder cancer, melanoma, estrogen receptor positive breast cancer, progesterone receptor positive breast cancer, hormone receptor positive breast cancer, brain cancer, colorectal cancer, kidney cancer, lung cancer, and most of the major subclasses and histological subtypes of hematopoietic cancer) or cancer related death (n=4860; 0.96, 0.91 to 1.02). Basal cell carcinoma risk was slightly increased for ever users (n=22 560; 1.05, 1.02 to 1.08). Cumulative dose was positively associated with risk of estrogen receptor negative breast cancer, progesterone receptor negative breast cancer, hormone receptor negative breast cancer, and ovarian cancer. An increased risk of Hodgkin lymphoma was observed only for women with naturally dark hair (based on 70 women, 24 with dark hair), and a higher risk of basal cell carcinoma was observed for women with naturally light hair. CONCLUSION: No positive association was found between personal use of permanent hair dye and risk of most cancers and cancer related mortality. The increased risk of basal cell carcinoma, breast cancer (estrogen receptor negative, progesterone receptor negative, hormone receptor negative) and ovarian cancer, and the mixed findings in analyses stratified by natural hair color warrant further investigation.


Assuntos
Carcinoma de Células Escamosas/induzido quimicamente , Tinturas para Cabelo/efeitos adversos , Enfermeiras e Enfermeiros/estatística & dados numéricos , Neoplasias Cutâneas/patologia , Adulto , Neoplasias Encefálicas/induzido quimicamente , Neoplasias da Mama/induzido quimicamente , Carcinoma Basocelular/induzido quimicamente , Estudos de Casos e Controles , Neoplasias Colorretais/induzido quimicamente , Feminino , Humanos , Neoplasias Renais/induzido quimicamente , Neoplasias Pulmonares/induzido quimicamente , Pessoa de Meia-Idade , Neoplasias Ovarianas/induzido quimicamente , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Neoplasias Cutâneas/mortalidade , Estados Unidos/epidemiologia , Neoplasias da Bexiga Urinária/induzido quimicamente
4.
JAMA Oncol ; 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32789511

RESUMO

Importance: Pancreatic cancer is the third-leading cause of cancer death in the United States; however, few high-risk groups have been identified to facilitate early diagnosis strategies. Objective: To evaluate the association of diabetes duration and recent weight change with subsequent risk of pancreatic cancer in the general population. Design, Setting, and Participants: This cohort study obtained data from female participants in the Nurses' Health Study and male participants in the Health Professionals Follow-Up Study, with repeated exposure assessments over 30 years. Incident cases of pancreatic cancer were identified from self-report or during follow-up of participant deaths. Deaths were ascertained through reports from the next of kin, the US Postal Service, or the National Death Index. Data collection was conducted from October 1, 2018, to December 31, 2018. Data analysis was performed from January 1, 2019, to June 30, 2019. Exposures: Duration of physician-diagnosed diabetes and recent weight change. Main Outcome and Measures: Hazard ratios (HRs) for subsequent development of pancreatic cancer. Results: Of the 112 818 women (with a mean [SD] age of 59.4 [11.7] years) and 46 207 men (with a mean [SD] age of 64.7 [10.8] years) included in the analysis, 1116 incident cases of pancreatic cancers were identified. Compared with participants with no diabetes, those with recent-onset diabetes had an age-adjusted HR for pancreatic cancer of 2.97 (95% CI, 2.31-3.82) and those with long-standing diabetes had an age-adjusted HR of 2.16 (95% CI, 1.78-2.60). Compared with those with no weight loss, participants who reported a 1- to 4-lb weight loss had an age-adjusted HR for pancreatic cancer of 1.25 (95% CI, 1.03-1.52), those with a 5- to 8-lb weight loss had an age-adjusted HR of 1.33 (95% CI, 1.06-1.66), and those with more than an 8-lb weight loss had an age-adjusted HR of 1.92 (95% CI, 1.58-2.32). Participants with recent-onset diabetes accompanied by weight loss of 1 to 8 lb (91 incident cases per 100 000 person-years [95% CI, 55-151]; HR, 3.61 [95% CI, 2.14-6.10]) or more than 8 lb (164 incident cases per 100 000 person-years [95% CI, 114-238]; HR, 6.75 [95% CI, 4.55-10.00]) had a substantially increased risk for pancreatic cancer compared with those with neither exposure (16 incident cases per 100 000 person-years; 95% CI, 14-17). Incidence rates were even higher among participants with recent-onset diabetes and weight loss with a body mass index of less than 25 before weight loss (400 incident cases per 100 000 person-years) or whose weight loss was not intentional judging from increased physical activity or healthier dietary choices (334 incident cases per 100 000 person-years). Conclusions and Relevance: This study demonstrates that recent-onset diabetes accompanied by weight loss is associated with a substantially increased risk for developing pancreatic cancer. Older age, previous healthy weight, and no intentional weight loss further elevate this risk.

5.
Gastroenterology ; 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32860791

RESUMO

BACKGROUND & AIMS: We evaluated the efficacy and safety of diet-modulated autologous fecal microbiota transplantation (aFMT) for treatment of weight regain after the weight loss phase. METHODS: In the DIRECT-PLUS weight loss trial (May 2017 through July 2018), abdominally obese or dyslipidemic participants in Israel were randomly assigned to (1)healthy dietary guidelines, (2)Mediterranean diet, and (3)green-Mediterranean diet weight-loss groups. All groups received free gym membership and physical activity guidelines. Both iso-caloric Mediterranean groups consumed 28g/day walnuts (+440mg/d polyphenols provided). The green-Mediterranean dieters further consumed green tea (3-4 cups/day) and a Wolffia-globosa (Mankai strain;100g/day) green shake (+800mg/day polyphenols provided). After 6 months (weight-loss phase), 90 eligible participants (mean age, 52 years; mean weight loss, 8.3 kg) provided a fecal sample that was processed into aFMT by frozen, opaque and odorless capsules. The participants were then randomly assigned to groups that received 100 capsules containing their own fecal microbiota or placebo until month 14. The primary outcome was regain of the lost weight over the expected weight regain phase (months 6-14). Secondary outcomes were gastrointestinal symptoms, waist-circumference, glycemic status and changes in the gut microbiome, as measured by metagenomic sequencing and 16s-rRNA. We validated the results in a parallel in-vivo study of mice specifically fed with Mankai, as compared to control chow diet. RESULTS: Of the 90 participants in the aFMT trial, 96% ingested at least 80 of 100 oral aFMT or placebo frozen capsules over the transplantation period. No aFMT-related adverse events or symptoms were observed. For the primary outcome, although no significant differences in weight regain were observed among the participants in the different lifestyle interventions during months 6-14 (aFMT, 30.4% vs. placebo, 40.6%;P=.28), aFMT significantly attenuated weight regain in the green-Mediterranean group (aFMT, 17.1%, vs placebo, 50%; P=.02), but not in the dietary guidelines (P=.57) or Mediterranean diet (P=.64) groups (P for the interaction=.03). Accordingly, aFMT attenuated waist circumference gain (aFMT, 1.89cm vs placebo, 5.05cm;P=.01) and insulin rebound (aFMT, 1.46±3.6µIU/ml vs placebo, 1.64±4.7µIU/ml;P=.04) in the green Mediterranean group but not in the dietary guidelines or Mediterranean diet (P for the interaction=.04 and .03, respectively). The green-Mediterranean diet was the only intervention to induce a significant change in microbiome composition during the weight loss phase, and to prompt preservation of weight loss-associated specific bacteria and microbial metabolic pathways (mainly microbial sugar transport) following the aFMT. In mice, Mankai-modulated aFMT in the weight loss phase, compared with control diet aFMT, significantly prevented weight regain, and resulted in better glucose tolerance, during a high-fat-diet induced regain phase (P<.05 for all). CONCLUSIONS: Autologous FMT, collected during the weight loss phase and administrated in the regain phase, might preserve weight loss and glycemic control and is associated with specific microbiome signatures. High-polyphenols, green plant-based or Mankai diet better optimizes the microbiome for an aFMT procedure. (ClinicalTrials.gov number, NCT03020186).

6.
Lancet Public Health ; 5(9): e475-e483, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32745512

RESUMO

BACKGROUND: Data for front-line health-care workers and risk of COVID-19 are limited. We sought to assess risk of COVID-19 among front-line health-care workers compared with the general community and the effect of personal protective equipment (PPE) on risk. METHODS: We did a prospective, observational cohort study in the UK and the USA of the general community, including front-line health-care workers, using self-reported data from the COVID Symptom Study smartphone application (app) from March 24 (UK) and March 29 (USA) to April 23, 2020. Participants were voluntary users of the app and at first use provided information on demographic factors (including age, sex, race or ethnic background, height and weight, and occupation) and medical history, and subsequently reported any COVID-19 symptoms. We used Cox proportional hazards modelling to estimate multivariate-adjusted hazard ratios (HRs) of our primary outcome, which was a positive COVID-19 test. The COVID Symptom Study app is registered with ClinicalTrials.gov, NCT04331509. FINDINGS: Among 2 035 395 community individuals and 99 795 front-line health-care workers, we recorded 5545 incident reports of a positive COVID-19 test over 34 435 272 person-days. Compared with the general community, front-line health-care workers were at increased risk for reporting a positive COVID-19 test (adjusted HR 11·61, 95% CI 10·93-12·33). To account for differences in testing frequency between front-line health-care workers and the general community and possible selection bias, an inverse probability-weighted model was used to adjust for the likelihood of receiving a COVID-19 test (adjusted HR 3·40, 95% CI 3·37-3·43). Secondary and post-hoc analyses suggested adequacy of PPE, clinical setting, and ethnic background were also important factors. INTERPRETATION: In the UK and the USA, risk of reporting a positive test for COVID-19 was increased among front-line health-care workers. Health-care systems should ensure adequate availability of PPE and develop additional strategies to protect health-care workers from COVID-19, particularly those from Black, Asian, and minority ethnic backgrounds. Additional follow-up of these observational findings is needed. FUNDING: Zoe Global, Wellcome Trust, Engineering and Physical Sciences Research Council, National Institutes of Health Research, UK Research and Innovation, Alzheimer's Society, National Institutes of Health, National Institute for Occupational Safety and Health, and Massachusetts Consortium on Pathogen Readiness.


Assuntos
Infecções por Coronavirus/transmissão , Pessoal de Saúde/estatística & dados numéricos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Equipamento de Proteção Individual/estatística & dados numéricos , Pneumonia Viral/transmissão , Adulto , Técnicas de Laboratório Clínico/estatística & dados numéricos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aplicativos Móveis , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Estudos Prospectivos , Medição de Risco , Autorrelato , Reino Unido/epidemiologia , Estados Unidos/epidemiologia , Adulto Jovem
8.
Carcinogenesis ; 41(7): 904-908, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32556091

RESUMO

DNA repair genes are commonly altered in metastatic prostate cancer, but BRCA1 mutations are rare. Preliminary studies suggest that higher tumor expression of the BRCA1 protein may be associated with worse prognosis. We undertook a prospective study among men with prostate cancer in the Health Professionals Follow-up Study and evaluated BRCA1 via immunohistochemical staining on tissue microarrays. BRCA1 was expressed in 60 of 589 tumors. Prevalence of BRCA1 positivity was 43% in the 14 men with metastases at diagnosis compared with 9% in non-metastatic tumors [difference, 33 percentage points; 95% confidence interval (CI), 7-59]. BRCA1-positive tumors had 2.16-fold higher Ki-67 proliferative indices (95% CI, 1.18-3.95), higher tumor aneuploidy as predicted from whole-transcriptome profiling, and higher Gleason scores. Among the 575 patients with non-metastatic disease at diagnosis, we evaluated the association between BRCA1 expression and development of lethal disease (metastasis or cancer-specific death, 69 events) during long-term follow-up (median, 18.3 years). A potential weak association of BRCA1 positivity with lethal disease (hazard ratio, 1.61; 95% CI, 0.82-3.15) was attenuated when adjusting for age, Gleason score and clinical stage (hazard ratio, 1.11; 95% CI, 0.54-2.29). In summary, BRCA1 protein expression is a feature of more proliferative and more aneuploid prostate tumors and is more common in metastatic disease. While not well suited as a prognostic biomarker in primary prostate cancer, BRCA1 protein expression may be most relevant in advanced disease.

9.
PLoS One ; 15(6): e0234391, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32525914

RESUMO

BACKGROUND: Pathological and clinical stage are associated with prostate cancer-specific survival after prostatectomy. With PSA screening, the post-surgery prognostic utility of clinical stage is debatable in studies seeking to identify new biomarkers. Few studies have investigated clinical stage and lethal prostate cancer association after accounting for pathological stage. We hypothesize that clinical stage provides prognostic information beyond pathological stage in the PSA era. METHODS: Cox regression models tested associations between clinical and pathological stage and lethal prostate cancer among 3,064 participants from the Health Professionals Follow-Up Study and Physicians' Health Study (HPFS/PHS) who underwent prostatectomy. Likelihood ratio tests and c-statistics were used to assess the models' prognostic utility. Equivalent analyses were performed in 16,134 men who underwent prostatectomy at Johns Hopkins. RESULTS: Independently, clinical and pathological stage were associated (p<0.0001 for both) with rate of lethal prostate cancer in HPFS/PHS. The model with clinical and pathological stage fit significantly better than the model with only pathological stage in all men (p = 0.01) and in men diagnosed during the PSA era (p = 0.04). The mutually adjusted model also improved discriminatory ability. In the Johns Hopkins cohort, the model with clinical and pathological stage improved discriminatory ability and fit significantly better overall (p<0.0001) and in the PSA era (p<0.0001). CONCLUSIONS: Despite stage migration resulting from widespread PSA screening, clinical stage remains associated with progression to lethal prostate cancer independent of pathological stage. Future studies evaluating associations between new factors and poor outcome following prostatectomy should consider including both clinical and pathological stages since the data is already available.


Assuntos
Calicreínas/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Prostatectomia , Neoplasias da Próstata/cirurgia , Estados Unidos
10.
Br J Cancer ; 123(5): 844-851, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32541871

RESUMO

BACKGROUND: Despite several plausible biological mechanisms linking proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs) with colorectal tumorigenesis, their association with risk of colorectal cancer (CRC) has not been adequately assessed in prospective epidemiological studies. METHODS: We evaluated the association of acid-suppressive medication use with CRC risk among 175,871 (PPI) and 208,831 (H2RA) participants from three large prospective cohort studies. Medication use was assessed at baseline and updated biennially. The association was evaluated using multivariate Cox proportional hazards regression models. RESULTS: There was no significant association between baseline PPI use (hazard ratio (HR) = 0.89, 95% confidence interval (CI), 0.71-1.12) or PPI use after a lag of 8-10 years (HR = 1.12, 95% CI, 0.78-1.59) with CRC risk. We observed no significant association between H2RA use after a lag of 8-10 years and CRC risk (HR = 1.02, 95% CI, 0.81-1.28), while risk was lower for participants with baseline H2RA use (HR = 0.76, 95% CI, 0.60-0.95). Duration of PPI use or H2RA use was not associated with CRC risk (P-trend = 0.21 and 0.95, respectively). CONCLUSIONS: Among participants from three large prospective cohorts, use of PPI or H2RA was not associated with higher risk of colorectal cancer.

11.
Am J Clin Nutr ; 112(3): 619-630, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32453379

RESUMO

BACKGROUND: Whether egg consumption is associated with the risk of type 2 diabetes (T2D) remains unsettled. OBJECTIVES: We evaluated the association between egg consumption and T2D risk in 3 large US prospective cohorts, and performed a systematic review and meta-analysis of prospective cohort studies. METHODS: We followed 82,750 women from the Nurses' Health Study (NHS; 1980-2012), 89,636 women from the NHS II (1991-2017), and 41,412 men from the Health Professionals Follow-up Study (HPFS; 1986-2016) who were free of T2D, cardiovascular disease, and cancer at baseline. Egg consumption was assessed every 2-4 y using a validated FFQ. We used Cox proportional hazard models to estimate HRs and 95% CIs. RESULTS: During a total of 5,529,959 person-years of follow-up, we documented 20,514 incident cases of T2D in the NHS, NHS II, and HPFS. In the pooled multivariable model adjusted for updated BMI, lifestyle, and dietary confounders, a 1-egg/d increase was associated with a 14% (95% CI: 7%, 20%) higher T2D risk. In random-effects meta-analysis of 16 prospective cohort studies (589,559 participants; 41,248 incident T2D cases), for each 1 egg/d, the pooled RR of T2D was 1.07 (95% CI: 0.99, 1.15; I2 = 69.8%). There were, however, significant differences by geographic region (P for interaction = 0.01). Each 1 egg/d was associated with higher T2D risk among US studies (RR: 1.18; 95% CI: 1.10, 1.27; I2 = 51.3%), but not among European (RR: 0.99; 95% CI: 0.85, 1.15; I2 = 73.5%) or Asian (RR: 0.82; 95% CI: 0.62, 1.09; I2 = 59.1%) studies. CONCLUSIONS: Results from the updated meta-analysis show no overall association between moderate egg consumption and risk of T2D. Whether the heterogeneity of the associations among US, European, and Asian cohorts reflects differences in egg consumption habits warrants further investigation.This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42019127860.


Assuntos
Diabetes Mellitus Tipo 2/etiologia , Dieta , Ovos , Ásia/epidemiologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Ovos/efeitos adversos , Europa (Continente)/epidemiologia , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Medição de Risco , Estados Unidos/epidemiologia
12.
Cancer Epidemiol Biomarkers Prev ; 29(5): 999-1008, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32321713

RESUMO

BACKGROUND: Pancreatic cancer is the third leading cause of cancer death in the United States, and 80% of patients present with advanced, incurable disease. Risk markers for pancreatic cancer have been characterized, but combined models are not used clinically to identify individuals at high risk for the disease. METHODS: Within a nested case-control study of 500 pancreatic cancer cases diagnosed after blood collection and 1,091 matched controls enrolled in four U.S. prospective cohorts, we characterized absolute risk models that included clinical factors (e.g., body mass index, history of diabetes), germline genetic polymorphisms, and circulating biomarkers. RESULTS: Model discrimination showed an area under ROC curve of 0.62 via cross-validation. Our final integrated model identified 3.7% of men and 2.6% of women who had at least 3 times greater than average risk in the ensuing 10 years. Individuals within the top risk percentile had a 4% risk of developing pancreatic cancer by age 80 years and 2% 10-year risk at age 70 years. CONCLUSIONS: Risk models that include established clinical, genetic, and circulating factors improved disease discrimination over models using clinical factors alone. IMPACT: Absolute risk models for pancreatic cancer may help identify individuals in the general population appropriate for disease interception.

13.
J Am Coll Cardiol ; 75(15): 1729-1739, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32147453

RESUMO

BACKGROUND: Olive oil intake has been associated with lower risk of cardiovascular disease (CVD) in Mediterranean populations, but little is known about these associations in the U.S population. OBJECTIVES: This study sought to examine whether olive oil intake is associated with total CVD, coronary heart disease (CHD), and stroke risk. METHODS: This study included 61,181 women from the Nurses' Health Study (1990 to 2014) and 31,797 men from the Health Professionals Follow-up Study (1990 to 2014) who were free of cancer, heart disease, and stroke at baseline. Diet was assessed using food frequency questionnaires at baseline and then every 4 years. Cox proportional hazards regressions were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During 24 years of follow-up, this study documented 9,797 incident cases of CVD, including 6,034 CHD cases and 3,802 stroke cases. After adjusting for major diet and lifestyle factors, compared with nonconsumers, those with higher olive oil intake (>0.5 tablespoon/day or >7 g/day) had 14% lower risk of CVD (pooled HR: 0.86; 95% CI: 0.79 to 0.94) and 18% lower risk of CHD (pooled HR: 0.82; 95% CI: 0.73 to 0.91). No significant associations were observed for total or ischemic stroke. Replacing 5 g/day of margarine, butter, mayonnaise, or dairy fat with the equivalent amount of olive oil was associated with 5% to 7% lower risk of total CVD and CHD. No significant associations were observed when olive oil was compared with other plant oils combined. In a subset of participants, higher olive oil intake was associated with lower levels of circulating inflammatory biomarkers and a better lipid profile. CONCLUSIONS: Higher olive oil intake was associated with lower risk of CHD and total CVD in 2 large prospective cohorts of U.S. men and women. The substitution of margarine, butter, mayonnaise, and dairy fat with olive oil could lead to lower risk of CHD and CVD.

14.
BMJ ; 368: m513, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32132002

RESUMO

OBJECTIVE: To evaluate the association between egg intake and cardiovascular disease risk among women and men in the United States, and to conduct a meta-analysis of prospective cohort studies. DESIGN: Prospective cohort study, and a systematic review and meta-analysis of prospective cohort studies. SETTING: Nurses' Health Study (NHS, 1980-2012), NHS II (1991-2013), Health Professionals' Follow-Up Study (HPFS, 1986-2012). PARTICIPANTS: Cohort analyses included 83 349 women from NHS, 90 214 women from NHS II, and 42 055 men from HPFS who were free of cardiovascular disease, type 2 diabetes, and cancer at baseline. MAIN OUTCOME MEASURES: Incident cardiovascular disease, which included non-fatal myocardial infarction, fatal coronary heart disease, and stroke. RESULTS: Over up to 32 years of follow-up (>5.54 million person years), 14 806 participants with incident cardiovascular disease were identified in the three cohorts. Participants with a higher egg intake had a higher body mass index, were less likely to be treated with statins, and consumed more red meats. Most people consumed between one and less than five eggs per week. In the pooled multivariable analysis, consumption of at least one egg per day was not associated with incident cardiovascular disease risk after adjustment for updated lifestyle and dietary factors associated with egg intake (hazard ratio for at least one egg per day v less than one egg per month 0.93, 95% confidence interval 0.82 to 1.05). In the updated meta-analysis of prospective cohort studies (33 risk estimates, 1 720 108 participants, 139 195 cardiovascular disease events), an increase of one egg per day was not associated with cardiovascular disease risk (pooled relative risk 0.98, 95% confidence interval 0.93 to 1.03, I2=62.3%). Results were similar for coronary heart disease (21 risk estimates, 1 411 261 participants, 59 713 coronary heart disease events; 0.96, 0.91 to 1.03, I2=38.2%), and stroke (22 risk estimates, 1 059 315 participants, 53 617 stroke events; 0.99, 0.91 to 1.07, I2=71.5%). In analyses stratified by geographical location (P for interaction=0.07), no association was found between egg consumption and cardiovascular disease risk among US cohorts (1.01, 0.96 to 1.06, I2=30.8%) or European cohorts (1.05, 0.92 to 1.19, I2=64.7%), but an inverse association was seen in Asian cohorts (0.92, 0.85 to 0.99, I2=44.8%). CONCLUSIONS: Results from the three cohorts and from the updated meta-analysis show that moderate egg consumption (up to one egg per day) is not associated with cardiovascular disease risk overall, and is associated with potentially lower cardiovascular disease risk in Asian populations. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019129650.


Assuntos
Doenças Cardiovasculares/etiologia , Ovos/efeitos adversos , Estudos de Coortes , Humanos , Estudos Prospectivos , Estados Unidos
15.
Med Sci Sports Exerc ; 52(8): 1729-1736, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32079915

RESUMO

PURPOSE: An inverse association between physical activity (PA) and risk of CHD has been seen in many studies, but evidence for benefits of PA after myocardial infarction (MI) in reducing mortality is limited. METHODS: Using data from the Health Professionals Follow-up Study cohort, we followed male survivors of MI. Short- and long-term changes in PA from before to after MI were calculated, and participants without ambulation impairment were classified into maintained low, decreased, increased, or maintained high PA categories. Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for mortality across PA and PA change categories. RESULTS: During a mean of 14 yr of follow-up of 1651 incident nonfatal MI cases, we documented 678 deaths, 307 were due to cardiovascular disease. The adjusted HR for all-cause mortality comparing ≥21 with ≤1.5 MET·wk of PA before MI was 0.73 (95% CI = 0.59-0.89, Ptrend = 0.03). Compared with men who maintained low PA before and after MI, men who maintained high PA had a 39% (95% CI = 25-50) lower risk of all-cause mortality, and those who had a long-term increase in PA from before to after MI had a 27% (95% CI = 6-43) lower risk. Walking for ≥30 min·d after MI was associated with a 29% lower mortality (HR = 0.71, 95% CI = 0.58-0.84), independent of walking pace, and walking pace after MI was inversely associated with mortality (HR = 0.67, 95% CI = 0.49-0.92). CONCLUSIONS: Maintaining a high PA or having a long-term increase in PA from before to after MI was associated with lower mortality among male MI survivors. Walking time and walking pace after MI were each inversely associated with mortality.

16.
BMJ ; 368: l6669, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915124

RESUMO

OBJECTIVE: To examine how a healthy lifestyle is related to life expectancy that is free from major chronic diseases. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: The Nurses' Health Study (1980-2014; n=73 196) and the Health Professionals Follow-Up Study (1986-2014; n=38 366). MAIN EXPOSURES: Five low risk lifestyle factors: never smoking, body mass index 18.5-24.9, moderate to vigorous physical activity (≥30 minutes/day), moderate alcohol intake (women: 5-15 g/day; men 5-30 g/day), and a higher diet quality score (upper 40%). MAIN OUTCOME: Life expectancy free of diabetes, cardiovascular diseases, and cancer. RESULTS: The life expectancy free of diabetes, cardiovascular diseases, and cancer at age 50 was 23.7 years (95% confidence interval 22.6 to 24.7) for women who adopted no low risk lifestyle factors, in contrast to 34.4 years (33.1 to 35.5) for women who adopted four or five low risk factors. At age 50, the life expectancy free of any of these chronic diseases was 23.5 (22.3 to 24.7) years among men who adopted no low risk lifestyle factors and 31.1 (29.5 to 32.5) years in men who adopted four or five low risk lifestyle factors. For current male smokers who smoked heavily (≥15 cigarettes/day) or obese men and women (body mass index ≥30), their disease-free life expectancies accounted for the lowest proportion (≤75%) of total life expectancy at age 50. CONCLUSION: Adherence to a healthy lifestyle at mid-life is associated with a longer life expectancy free of major chronic diseases.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Estilo de Vida Saudável/fisiologia , Expectativa de Vida , Neoplasias , Comportamento de Redução do Risco , Adulto , Consumo de Bebidas Alcoólicas , Índice de Massa Corporal , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/psicologia , Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Mellitus Tipo 2/psicologia , Dieta Saudável , Exercício Físico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/prevenção & controle , Neoplasias/psicologia , Pesquisa em Enfermagem , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Fumar
17.
Int J Cancer ; 146(9): 2394-2405, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31276202

RESUMO

Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all ptrend < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.

18.
Int J Cancer ; 146(9): 2442-2449, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31304976

RESUMO

Tea and coffee have antioxidant and neuroprotective effects. Observational studies suggest that tea and coffee intake may reduce cancer risk, but data on glioma risk are inconclusive. We evaluated the association between tea, coffee and caffeine intake and glioma risk in the female Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII) and the male Health Professionals Follow-Up Study (HPFS). Cumulative intake was derived from validated quadrennial food frequency questionnaires. Glioma cases were confirmed by medical record review. Multivariable-adjusted hazard ratios of glioma by beverage intake category were estimated using Cox proportional hazards models. We documented 554 incident cases of glioma (256 in NHS, 87 in NHSII and 211 in HPFS). Compared to <1 cup/week, higher tea consumption was borderline inversely associated with glioma risk in pooled cohorts (hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.49-1.10 for >2 cups/day, p-trend = 0.05), but not in women (HR = 0.74, 95% CI: 0.47-1.18 for >2 cups/day, p-trend = 0.11) or men (HR = 0.70, 95% CI: 0.30-1.60 for >2 cups/day, p-trend = 0.30) separately. Overall, we observed no significant associations between caffeinated, decaffeinated or total coffee intake and glioma risk. There were no material differences in the results with baseline values, 8-year lagged responses, or when limited to glioblastoma (n = 362). In three large prospective cohort studies, tea intake was borderline inversely associated with glioma risk. No significant associations were observed for coffee intake and glioma risk. These results merit further exploration in prospective studies.

19.
Eur J Epidemiol ; 35(2): 93-97, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31761964

RESUMO

In recent years, epidemiologists have increasingly sought to employ genetic data to identify 'causal' relationships between exposures of interest and various endpoints - an instrumental variable approach sometimes termed Mendelian randomization. However, this approach is subject to all of the limitations of instrumental variable analysis and to several limitations specific to its genetic underpinnings, including confounding, weak instrument bias, pleiotropy, adaptation, and failure of replication. Although the approach enjoys some utility in testing the etiological role of discrete biochemical pathways, like folate metabolism, examples like that of alcohol consumption and cardiovascular disease demonstrate that it must be treated with all of the circumspection that should accompany all forms of observational epidemiology. Going forward, we urge the elimination of randomization or causality in reports of its use and suggest that Mendelian randomization instead be termed exactly what it is - genetic instrumental variable analysis.


Assuntos
Consumo de Bebidas Alcoólicas , Doenças Cardiovasculares , Pleiotropia Genética , Variação Genética , Análise da Randomização Mendeliana/métodos , Consumo de Bebidas Alcoólicas/genética , Viés , Doenças Cardiovasculares/genética , Métodos Epidemiológicos , Estudo de Associação Genômica Ampla/métodos , Humanos , Epidemiologia Molecular
20.
Clin Cancer Res ; 26(5): 1086-1093, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31754047

RESUMO

PURPOSE: Statins are associated with lower risk of aggressive prostate cancer, but lethal prostate cancer is understudied and contributing mechanisms are unclear. We prospectively examined statins and lethal prostate cancer risk in the Health Professionals Follow-up Study (HPFS), tested associations with molecular subtypes, and integrated gene expression profiling to identify putative mechanisms. EXPERIMENTAL DESIGN: Our study included 44,126 men cancer-free in 1990, followed for prostate cancer incidence through 2014, with statin use recorded on biennial questionnaires. We used multivariable Cox regression to examine associations between statins and prostate cancer risk overall, by measures of clinically significant disease, and by ERG and PTEN status. In an exploratory analysis, age-adjusted gene set enrichment analysis identified statin-associated pathways enriched in tumor and adjacent normal prostate tissue. RESULTS: During 24 years of follow-up, 6,305 prostate cancers were diagnosed and 801 (13%) were lethal (metastatic at diagnosis or metastatic/fatal during follow-up). Relative to never/past use, current statin use was inversely associated with risk of lethal prostate cancer [HR, 0.76; 95% confidence interval (CI), 0.60-0.96] but not overall disease. We found a strong inverse association for risk of PTEN-null cancers (HR, 0.40; 95% CI, 0.19-0.87) but not PTEN-intact cancers (HR, 1.18; 95% CI, 0.95-1.48; P heterogeneity = 0.01). Associations did not differ by ERG. Inflammation and immune pathways were enriched in normal prostate tissue of statin ever (n = 10) versus never users (n = 103). CONCLUSIONS: Molecular tumor classification identified PTEN and inflammation/immune activation as potential mechanisms linking statins with lower lethal prostate cancer risk. These findings support a potential causal association and could inform selection of relevant biomarkers for statin clinical trials.

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