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1.
Dig Dis Sci ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33403483

RESUMO

BACKGROUND AND AIMS: Tissue miRNA can discriminate between esophageal adenocarcinoma (EA) and normal epithelium. However, no studies have examined a comprehensive panel of circulating miRNAs in relation to EA diagnosis and survival. METHODS: We used all 62 EA cases from the US Multi-Center case-control study with available serum matched 1:1 to controls. Cases were followed for vital status. MiRNAs (n = 2064) were assessed using the HTG EdgeSeq miRNA Whole Transcriptome Assay. Differential expression analysis of miRNAs in relation to case-control status was conducted. In cases, Cox regression models were fit to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. P values were adjusted using the Benjamini-Hochberg (BH) procedure for false discovery rate control. Predictive performance was assessed using cross-validation. RESULTS: Sixty-eight distinct miRNAs were significantly upregulated between cases and controls (e.g., miR-1255b-2-3p fold change = 1.74, BH-adjusted P = 0.01). Assessing the predictive performance of these significantly upregulated miRNAs yielded 60% sensitivity, 65% specificity, and 0.62 AUC. miR-4253 and miR-1238-5p were associated with risk of mortality after EA diagnosis (HR = 4.85, 95% CI: 2.30-10.23, BH-adjusted P = 0.04 and HR = 3.81, 95% CI: 2.02-7.19, BH-adjusted P = 0.04, respectively). CONCLUSIONS: While they require replication, these findings suggest that circulating miRNAs may be associated with EA diagnosis and survival.

2.
Gastrointest Endosc Clin N Am ; 31(1): 1-26, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33213789

RESUMO

In the United States, the incidence of esophageal adenocarcinoma increased markedly since the 1970s with a recent stabilization. Despite evolving screening and surveillance strategies to diagnose, risk triage, and intervene in Barrett's esophagus patients to prevent esophageal adenocarcinoma, most cases present with advanced disease and poor resultant survival. Epidemiologic studies have identified the main risk factors for these conditions, including increasing age, male sex, white race, gastroesophageal reflux disease, abdominal obesity, cigarette smoking, and lack of infection with Helicobacter pylori. This review summarizes the current epidemiologic evidence with implications for screening and surveillance in Barrett's esophagus and esophageal adenocarcinoma.

3.
Am J Gastroenterol ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33229980

RESUMO

INTRODUCTION: Using the National Cancer Database, we assessed the relationship between facility overall esophageal adenocarcinoma (EAC) case volume and survival. METHODS: We categorized facilities into volume quintiles based on annual EAC patient volume and performed a multivariable Cox proportional hazards regression between facility patient volume and survival. RESULTS: In a cohort of 116,675 patients, facilities with higher vs lower (≥25 vs 1-4 cases) annual EAC patient volume demonstrated improved survival (adjusted hazard ratio: 0.80. 95% confidence interval: 0.70-0.91). DISCUSSION: This robust volume-outcome effect calls for centralization of care for EAC patients at high annual case volume facilities.

4.
Cancer Med ; 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33219755

RESUMO

BACKGROUND: Despite the high incidence and mortality of prostate cancer (PCa) in the Unites States, few risk factors have been consistently linked with these PCa outcomes. Assessing proxies of reproductive factors may offer insights into PCa pathogenesis. In this study, we examined fatherhood status as a proxy of fertility in relation to total, nonaggressive, aggressive, and fatal PCa. METHODS: We examined participants of two cohorts, the NIH-AARP Diet and Health (NIH-AARP) Study and Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals of associations between fatherhood status and number of children sired in relation to PCa incidence. RESULTS: Fatherhood status (one or more children vs. childless) was positively associated with total PCa risk in NIH-AARP or PLCO, but was not statistically significant (p = 0.06 and 0.55, respectively). Number of children sired indicated a slightly elevated risk of total PCa, but HRs were rarely significant and were of a fairly constant magnitude with no discernable trend relative to the childless referent group. Associations were similar for nonaggressive and aggressive PCa. The trend test for fatal PCa was statistically significant in NIH-AARP (ptrend  < 0.01), despite none of the individual categorical point estimates reaching this threshold. CONCLUSION: This study provides tentative evidence that fathering children is associated with a slightly increased PCa risk. Future research should strive to assess better proxies of reproductive function in relation to aggressive and fatal PCa to provide more specific evidence for this putative relationship.

5.
Am J Gastroenterol ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33156012

RESUMO

INTRODUCTION: Gastrointestinal cancers show an unexplained male predominance, but few prospective studies have investigated sex hormones and gastrointestinal cancer risk. This study aimed to determine the impact of circulating sex hormones on risk of esophageal, gastric, and colorectal cancers in men and women. METHODS: We included 219,425 men and 147,180 women from the UK Biobank. Sex hormones were quantified using chemiluminescent immunoassay. Gastrointestinal cancers were identified from cancer registry linkages. Sex hormone concentrations and risk of gastrointestinal cancers were investigated using Cox proportional hazards regression. RESULTS: During the 10 years of follow-up, 376 esophageal adenocarcinoma, 108 esophageal squamous cell carcinoma, and 333 gastric and 2,868 colorectal cancer cases were identified. Increased hazard ratios (HRs) were found for sex hormone-binding globulin (SHBG) and risk of gastric cancer in men (Q4 vs Q1 HR 1.43, 95% confidence interval [CI] 0.95-2.17, Ptrend = 0.01). Free testosterone was inversely associated with esophageal squamous cell carcinoma in women (Q4 vs Q1 HR 0.32, 95% CI 0.11-0.98, Ptrend = 0.05). For colorectal cancer, SHBG was associated with a reduced risk among men (Q4 vs Q1 HR 0.89, 95% CI 0.77-1.03, Ptrend = 0.04) and free testosterone concentrations was associated with a reduction in risk among women (Q4 vs Q1 HR 0.80, 95% CI 0.66-0.97, Ptrend = 0.01). No associations were found for esophageal adenocarcinoma. DISCUSSION: In this large prospective investigation of prediagnostic sex hormones and risk of gastrointestinal cancers, men with higher SHBG concentrations had higher gastric, yet lower colorectal, cancer risks, whereas women with higher free testosterone levels had a lower risk of esophageal squamous cell carcinoma and colorectal cancer.

6.
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.

7.
Eur Urol ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33092896

RESUMO

BACKGROUND: In the USA, it is unknown whether metastatic prostate cancer incidence has continued to increase and whether racial differences have persisted. OBJECTIVE: Combining multiple imputation with age and delay adjustment, we provide an up-to-date, comprehensive assessment of US prostate cancer incidence trends by stage and race. DESIGN, SETTING, AND PARTICIPANTS: From Surveillance Epidemiology and End Results (SEER)-18, 774 240 prostate cancer cases were diagnosed during 2004-2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multiple imputation assigned prostate cancer stage to the 4.7% of cases with missing stage, which varied by year and race-ethnicity. SEER delay factors adjusted case counts to anticipated future data corrections. Twenty datasets were imputed, and Rubin's rules were used for summary estimation. Overall and stage-specific rates were estimated and stratified by race and age group. Joinpoint software identified significant temporal changes and estimated annual percentage changes. We compared these estimates without multiple imputation and delay adjustment. RESULTS AND LIMITATIONS: Metastatic prostate cancer incidence increased during 2011-2017, with an annual percentage change of 5.5. This was followed by increases in localized and regional disease since 2014. Non-Hispanic black men continued to have the highest incidence, especially for metastatic disease. The increasing rate of metastatic prostate cancer in non-Hispanic white men aged 50-74 yr accelerated recently, and the incidence was 56% higher in 2017 than in 2004. Rates without multiple imputation and delay adjustment were quantitatively and qualitatively different. This observational study is unable to assign causes to observed changes in prostate cancer incidence. CONCLUSIONS: Multiple imputation and delay adjustment are essential for portraying accurately stage- and race-specific prostate cancer incidence as clinical practice evolves. PATIENT SUMMARY: In the USA, diagnosis of prostate cancer that has spread to distant sites (metastatic disease) continues to increase. Black men continue to have higher risks of being diagnosed with metastatic prostate cancer than other race-ethnicities.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33104910

RESUMO

PURPOSE: Daily aspirin use has been shown to reduce risk of colorectal, and possibly other, cancers, but it is unknown if these benefits are consistent across subgroups of people with differing cancer risk factors. We investigated whether age, body mass index (BMI), smoking status, physical inactivity, and family history of cancer modify the effect of daily aspirin use on colorectal, ovarian, breast, endometrial and aggressive prostate cancer risk. METHODS: We pooled 423,495 individuals from two prospective, U.S.-based studies: the NIH-AARP Diet and Health Study (1995-2011) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (1993-2009). Using Cox proportional hazards regression, we examined associations between daily aspirin use (≥ 5 days/week) and risk of colorectal, ovarian, breast, endometrial, and aggressive prostate cancer, overall and across strata of risk factors. RESULTS: Daily aspirin use was associated with a 15% reduction in colorectal cancer risk (hazard ratio [HR]: 0.85, 95% confidence interval [CI] 0.80-0.89). Risk reductions were generally consistent across strata of risk factors but attenuated with increasing BMI (p-interaction = 0.16). For ovarian cancer, there was no significant association overall (HR: 0.93, 95% CI 0.80-1.08) but reduced risk among obese women (HR: 0.73, 95% CI 0.52-0.98, p-interaction = 0.12). Weak or null associations were observed for breast, endometrial, and aggressive prostate cancer, with no strong effect modification observed. CONCLUSIONS: Daily aspirin use appears to reduce colorectal cancer risk regardless of other risk factors, though the potential modifying effect of BMI warrants further investigation and may need to be considered in risk-benefit calculations for aspirin use.

9.
Gastroenterology ; 159(6): 2065-2076.e1, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32918910

RESUMO

BACKGROUND & AIMS: Esophageal adenocarcinoma (EA) and its premalignant lesion, Barrett's esophagus (BE), are characterized by a strong and yet unexplained male predominance (with a male-to-female ratio in EA incidence of up to 6:1). Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for these conditions. However, potential sex differences in genetic associations with BE/EA remain largely unexplored. METHODS: Given strong genetic overlap, BE and EA cases were combined into a single case group for analysis. These were compared with population-based controls. We performed sex-specific GWAS of BE/EA in 3 separate studies and then used fixed-effects meta-analysis to provide summary estimates for >9 million variants for male and female individuals. A series of downstream analyses were conducted separately in male and female individuals to identify genes associated with BE/EA and the genetic correlations between BE/EA and other traits. RESULTS: We included 6758 male BE/EA cases, 7489 male controls, 1670 female BE/EA cases, and 6174 female controls. After Bonferroni correction, our meta-analysis of sex-specific GWAS identified 1 variant at chromosome 6q11.1 (rs112894788, KHDRBS2-MTRNR2L9, PBONF = .039) that was statistically significantly associated with BE/EA risk in male individuals only, and 1 variant at chromosome 8p23.1 (rs13259457, PRSS55-RP1L1, PBONF = 0.057) associated, at borderline significance, with BE/EA risk in female individuals only. We also observed strong genetic correlations of BE/EA with gastroesophageal reflux disease in male individuals and obesity in female individuals. CONCLUSIONS: The identified novel sex-specific variants associated with BE/EA could improve the understanding of the genetic architecture of the disease and the reasons for the male predominance.

10.
Cancer Causes Control ; 31(11): 1011-1019, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32839916

RESUMO

PURPOSE: Previous studies have shown an overall decreased risk of second cancers among prostate cancer survivors, but this has not been comprehensively examined by race/ethnicity. We conducted a retrospective cohort study of 716,319 one-year survivors of prostate cancer diagnosed at ages 35-84 during 2000-2015 as reported to 17 US Surveillance, Epidemiology and End Results (SEER) registries. METHODS: We estimated standardized incidence ratios (SIRs) for second primary non-prostate malignancies by race/ethnicity (non-Latino white, Black, Asian/Pacific Islander [API] and Latino), by Gleason, and by time since prostate cancer diagnosis. Poisson regression models were used to test heterogeneity between groups with the expected number as the offset. RESULTS: 60,707 second primary malignancies were observed. SIRs for all second cancers combined varied significantly by race/ethnicity: SIRwhite: 0.88 (95% confidence interval: 0.87-0.89), SIRLatino: 0.92 (0.89-0.95), SIRBlack: 0.97 (0.95-0.99), and SIRAPI: 1.05 (1.01-1.09) (p-heterogeneity < 0.001). SIRs for all cancers combined were higher among survivors of higher vs. lower Gleason prostate cancers irrespective of race/ethnicity. We observed significant heterogeneity by race/ethnicity in SIRs for 9 of 14 second cancer types investigated including lung, bladder, kidney, and liver. CONCLUSIONS: Our results confirm that most prostate cancer survivors have lower risks of second cancers than expected, but the magnitude varied by race/ethnicity. Exceptionally, API men had small but significantly increased risk. Further research to understand drivers of the observed race/ethnicity heterogeneity is warranted.


Assuntos
Sobreviventes de Câncer , Segunda Neoplasia Primária/epidemiologia , Neoplasias da Próstata/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupos Étnicos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Risco , Programa de SEER , Estados Unidos
11.
Int J Cancer ; 147(10): 2669-2676, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32350862

RESUMO

Obesity has been associated with an increased risk of advanced prostate cancer. However, most studies have been conducted among North American and European populations. Prostate cancer mortality appears elevated in West Africa, yet risk factors for prostate cancer in this region are unknown. We thus examined the relationship between obesity and prostate cancer using a case-control study conducted in Accra, Ghana in 2004 to 2012. Cases and controls were drawn from a population-based sample of 1037 men screened for prostate cancer, yielding 73 cases and 964 controls. An additional 493 incident cases were recruited from the Korle-Bu Teaching Hospital. Anthropometric measurements were taken at enrollment. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR) and prostate cancer, adjusting for potential confounders. The mean BMI was 25.1 kg/m2 for cases and 24.3 kg/m2 for controls. After adjustment, men with BMI ≥ 30 kg/m2 had an increased risk of prostate cancer relative to men with BMI < 25 kg/m2 (OR 1.86, 95% CI 1.11-3.13). Elevated WC (OR 1.76, 95% CI 1.24-2.51) and WHR (OR 1.46, 95% CI 0.99-2.16) were also associated with prostate cancer. Associations were not modified by smoking status and were evident for low- and high-grade disease. These findings indicate that overall and abdominal obesity are positively associated with prostate cancer among men in Ghana, implicating obesity as a potentially modifiable risk factor for prostate cancer in this region.

12.
Br J Cancer ; 123(3): 487-494, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32433602

RESUMO

BACKGROUND: Differential uptake of prostate-specific antigen testing in the US and UK has been linked to between-country differences for prostate cancer incidence. We examined stage-specific fatal prostate cancer incidence trends in the US and England, by treatment and race/ethnicity. METHODS: Using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program and Public Health England's National Cancer Registration and Analysis Service, we identified prostate cancer patients diagnosed between 1995 and 2005, aged 45-84 years. Fatal prostate cancer was defined as death attributed to the disease within 10 years of diagnosis. We used age-period-cohort models to assess trends in fatal prostate cancer incidence. RESULTS: Fatal prostate cancer incidence declined in the US by -7.5% each year and increased in England by 7.7% annually. These trends were primarily driven by locoregional disease in the US and distant disease in England. Black men in both countries had twofold to threefold higher fatal prostate cancer incidence rates, when compared with their white counterparts; however, receipt of radical prostatectomy lessened this disparity. CONCLUSIONS: We report a significant increasing rate of fatal prostate cancer incidence among English men. The black-white racial disparity appears pervasive but is attenuated among those who received radical prostatectomy in the US.

13.
Am J Epidemiol ; 189(10): 1096-1113, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32141493

RESUMO

Recent epidemiologic studies have examined the association of fish consumption with upper gastrointestinal cancer risk, but the associations with n-3 and n-6 polyunsaturated fatty acid (PUFA) subtypes remain unclear. Using the National Institutes of Health-AARP Diet and Health Study (United States, 1995-2011), we prospectively investigated the associations of PUFA subtypes, ratios, and fish with the incidence of head and neck cancer (HNC; n = 2,453), esophageal adenocarcinoma (EA; n = 855), esophageal squamous cell carcinoma (n = 267), and gastric cancer (cardia: n = 603; noncardia: n = 631) among 468,952 participants (median follow-up, 15.5 years). A food frequency questionnaire assessed diet. Multivariable-adjusted hazard ratios were estimated using Cox proportional hazards regression. A Benjamini-Hochberg (BH) procedure was used for false-discovery control. Long-chain n-3 PUFAs were associated with a 20% decreased HNC and EA risk (for HNC, quintile5 vs. 1 hazard ratio = 0.81, 95% confidence interval: 0.71, 0.92, and BH-adjusted Ptrend = 0.001; and for EA, quintile5 vs. 1 hazard ratio = 0.79, 95% confidence interval: 0.64, 0.98, and BH-adjusted Ptrend = 0.1). Similar associations were observed for nonfried fish but only for high intake. Further, the ratio of long-chain n-3:n-6 was associated with a decreased HNC and EA risk. No consistent associations were observed for gastric cancer. Our results indicate that dietary long-chain n-3 PUFA and nonfried fish intake are associated with lower HNC and EA risk.


Assuntos
Neoplasias Esofágicas/epidemiologia , Ácidos Graxos Insaturados/administração & dosagem , Neoplasias de Cabeça e Pescoço/epidemiologia , Alimentos Marinhos/estatística & dados numéricos , Neoplasias Gástricas/epidemiologia , Adenocarcinoma/epidemiologia , Idoso , Animais , Carcinoma de Células Escamosas/epidemiologia , Estudos de Coortes , Feminino , Peixes , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia
14.
Am J Gastroenterol ; 115(2): 211-213, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32023229

RESUMO

Esophageal adenocarcinoma (EA) incidence is 4-8 times higher in men compared with women, yet this imbalance cannot be explained by known risk factors. This issue of The American Journal of Gastroenterology features results from only the second prospective study to assess whether prediagnostic sex steroid hormones underlie sex differences in EA. Xie et al. report that higher concentrations of testosterone and luteinizing hormone were associated with decreased EA risk. While contrary to the long-standing hypothesis that testosterone increases EA risk, these important results lay a foundation for additional studies to further elucidate this intuitive, intriguing, and evolving hypothesis.


Assuntos
Adenocarcinoma , Feminino , Hormônios Esteroides Gonadais , Humanos , Incidência , Masculino , Estudos Prospectivos , Testosterona
15.
J Urol ; 203(6): 1184-1190, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31928462

RESUMO

PURPOSE: We explored the Medicare database (1999 to 2014) to provide a comprehensive assessment of testosterone therapy patterns in the older U.S. male population. MATERIALS AND METHODS: We estimated annual age-standardized incidence (new users) and prevalence (existing users) of testosterone therapy according to demographic characteristics, comorbidities and potential indications. RESULTS: There were 392,698 incident testosterone therapy users during 88 million person-years. Testosterone therapy users were predominantly younger, white nonHispanic, and located in South and West U.S. Census regions. On average testosterone therapy use increased dramatically during 2007 to 2014 (average annual percent change 15.5%), despite a decrease in 2014. In 2014 the most common recorded potential indications for any testosterone therapy were hypogonadism (48%), fatigue (18%), erectile dysfunction (15%), depression (4%) and psychosexual dysfunction (1%). Laboratory tests to measure circulating testosterone concentrations for testosterone therapy were infrequent with 35% having had at least 1 testosterone test in the 120 days preceding testosterone therapy, 4% the recommended 2 pre-testosterone therapy tests, and 16% at least 1 pre-testosterone therapy test and at least 1 post-testosterone therapy test. CONCLUSIONS: Testosterone therapy remains common in the older U.S. male population, despite a recent decrease. Although testosterone therapy prescriptions are predominantly for hypogonadism, a substantial proportion appear to be for less specific conditions. Testosterone tests among men prescribed testosterone therapy appear to be infrequent.


Assuntos
Androgênios/uso terapêutico , Uso de Medicamentos/tendências , Terapia de Reposição Hormonal/tendências , Padrões de Prática Médica/tendências , Testosterona/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Depressão/tratamento farmacológico , Disfunção Erétil/tratamento farmacológico , Fadiga/tratamento farmacológico , Humanos , Hipogonadismo/tratamento farmacológico , Estudos Longitudinais , Masculino , Medicare , Estudos Retrospectivos , Estados Unidos
16.
J Clin Oncol ; 38(7): 686-697, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31877085

RESUMO

PURPOSE: To determine whether recommended amounts of leisure-time physical activity (ie, 7.5-15 metabolic equivalent task [MET] hours/week) are associated with lower cancer risk, describe the shape of the dose-response relationship, and explore associations with moderate- and vigorous-intensity physical activity. METHODS: Data from 9 prospective cohorts with self-reported leisure-time physical activity and follow-up for cancer incidence were pooled. Multivariable Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% CIs of the relationships between physical activity with incidence of 15 types of cancer. Dose-response relationships were modeled with restricted cubic spline functions that compared 7.5, 15.0, 22.5, and 30.0 MET hours/week to no leisure-time physical activity, and statistically significant associations were determined using tests for trend (P < .05) and 95% CIs (< 1.0). RESULTS: A total of 755,459 participants (median age, 62 years [range, 32-91 years]; 53% female) were followed for 10.1 years, and 50,620 incident cancers accrued. Engagement in recommended amounts of activity (7.5-15 MET hours/week) was associated with a statistically significant lower risk of 7 of the 15 cancer types studied, including colon (8%-14% lower risk in men), breast (6%-10% lower risk), endometrial (10%-18% lower risk), kidney (11%-17% lower risk), myeloma (14%-19% lower risk), liver (18%-27% lower risk), and non-Hodgkin lymphoma (11%-18% lower risk in women). The dose response was linear in shape for half of the associations and nonlinear for the others. Results for moderate- and vigorous-intensity leisure-time physical activity were mixed. Adjustment for body mass index eliminated the association with endometrial cancer but had limited effect on other cancer types. CONCLUSION: Health care providers, fitness professionals, and public health practitioners should encourage adults to adopt and maintain physical activity at recommended levels to lower risks of multiple cancers.

17.
Cancer Epidemiol Biomarkers Prev ; 29(1): 236-245, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31641011

RESUMO

BACKGROUND: We conducted a study to assess whether testosterone therapy (TT) alters prostate cancer risk using a large U.S. commercial insurance research database. METHODS: From the HealthCore Integrated Research Database (HIRD), we selected men ages 30 years or greater who were new users of TT during 2007 to 2015. We selected two comparison groups: (i) unexposed (matched 10:1) and (ii) new users of phosphodiesterase type 5 inhibitor (PDE5i). Incident prostate cancer was defined as diagnosis of prostate cancer within 4 weeks following prostate biopsy. Propensity scores and inverse probability of treatment weights were used in Poisson regression models to estimate adjusted incidence rates, incidence rate ratios (IRR), and 95% confidence intervals (CI). Subgroup analyses included stratification by prostate cancer screening, hypogonadism, and follow-up time. RESULTS: The adjusted prostate cancer IRR was 0.77 (95% CI, 0.68-0.86) when comparing TT with the unexposed group and 0.85 (95% CI, 0.79-0.91) in comparison with the PDE5i group. Inverse associations between TT and prostate cancer were observed in a majority of subgroup analyses, although in both comparisons estimates generally attenuated with increasing time following initial exposure. Among TT users, duration of exposure was not associated with prostate cancer. CONCLUSIONS: Men who received TT did not have a higher rate of prostate cancer compared with the unexposed or PDE5i comparison groups. The inverse association between TT and prostate cancer could be the result of residual confounding, contraindication bias, or undefined biological effect. IMPACT: This study suggests that limited TT exposure does not increase risk of prostate cancer in the short term.

18.
Epidemiology ; 31(3): 432-440, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31651660

RESUMO

BACKGROUND: Androgen deprivation therapy (ADT), with a proven role in prostate cancer management, has been associated with various cardiovascular diseases. However, few studies have investigated these associations by type of ADT, particularly for newer ADTs such as the gonadotropin-releasing hormone (GnRH) antagonist degarelix. We investigated the risk of cardiovascular disease by type of ADT in a real-world setting. METHODS: We identified men newly diagnosed with prostate cancer, from 2009 to 2015, from the Scottish Cancer Registry and ADTs from the nationwide Prescribing Information System. Cardiovascular events were based upon hospitalization (from hospital records) or death from cardiovascular disease (from death records). We used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular events with time-varying ADT exposure, comparing ADT users with untreated patients, after adjusting for potential confounders, including prior cardiovascular disease. RESULTS: The cohort contained 20,216 prostate cancer patients, followed for 73,570 person-years, during which there were 3,853 cardiovascular events. ADT was associated with a 30% increase in cardiovascular events (adjusted HR = 1.3; 95% CI = 1.2, 1.4). This reflected increases in cardiovascular events associated with GnRH agonists (adjusted HR = 1.3; 95% CI = 1.2, 1.4), degarelix (adjusted HR = 1.5; 95% CI = 1.2, 1.9), but not bicalutamide monotherapy (adjusted HR = 1.0; 95% CI = 0.82, 1.3). CONCLUSIONS: There were increased risks of cardiovascular disease with the use of GnRH agonists and degarelix, but not with bicalutamide monotherapy. This is the first study to observe increased cardiovascular risks with degarelix, but the cause of this association is unclear and merits further investigation.

19.
Cancer ; 125(23): 4210-4223, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31490550

RESUMO

BACKGROUND: Diabetes is positively associated with various cancers, but its relationship with tumors of the esophagus/esophagogastric junction remains unclear. METHODS: Data were harmonized across 13 studies in the International Barrett's and Esophageal Adenocarcinoma Consortium, comprising 2309 esophageal adenocarcinoma (EA) cases, 1938 esophagogastric junction adenocarcinoma (EGJA) cases, 1728 Barrett's esophagus (BE) cases, and 16,354 controls. Logistic regression was used to estimate study-specific odds ratios (ORs) and 95% CIs for self-reported diabetes in association with EA, EGJA, and BE. Adjusted ORs were then combined using random-effects meta-analysis. RESULTS: Diabetes was associated with a 34% increased risk of EA (OR, 1.34; 95% CI, 1.00-1.80; I2  = 48.8% [where 0% indicates no heterogeneity, and larger values indicate increasing heterogeneity between studies]), 27% for EGJA (OR, 1.27; 95% CI, 1.05-1.55; I2  = 0.0%), and 30% for EA/EGJA combined (OR, 1.30; 95% CI, 1.06-1.58; I2  = 34.9%). Regurgitation symptoms modified the diabetes-EA/EGJA association (P for interaction = .04) with a 63% increased risk among participants with regurgitation (OR, 1.63; 95% CI, 1.19-2.22), but not among those without regurgitation (OR, 1.03; 95% CI, 0.74-1.43). No consistent association was found between diabetes and BE. CONCLUSIONS: Diabetes was associated with increased EA and EGJA risk, which was confined to individuals with regurgitation symptoms. Lack of an association between diabetes and BE suggests that diabetes may influence progression of BE to cancer.


Assuntos
Adenocarcinoma/complicações , Esôfago de Barrett/complicações , Diabetes Mellitus/etiologia , Neoplasias Esofágicas/complicações , Adenocarcinoma/patologia , Esôfago de Barrett/patologia , Estudos de Casos e Controles , Diabetes Mellitus/patologia , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Obesity (Silver Spring) ; 27(9): 1520-1526, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31380608

RESUMO

OBJECTIVE: Esophageal adenocarcinoma (EA) and gastric cardia adenocarcinoma (GCA) are among the most rapidly increasing cancers in Western countries. Elevated BMI in adulthood is a known risk factor, but associations in early life are unclear. METHODS: This study assessed weight change between childhood and early adulthood in relation to EA/GCA. Measured weights and heights during childhood (7-13 years) and early adulthood (17-26 years) were available for 64,695 young men from the Copenhagen School Health Records Register and the Danish Conscription Database. Individuals were categorized as having normal weight or overweight. Linkage with the Danish Cancer Registry identified 275 EA/GCA cases. Hazard ratios (HR) and 95% CI were estimated using Cox proportional hazards regression. RESULTS: The risk of EA/GCA was 2.5 times higher in men who were first classified as having overweight at age 7 (HR = 2.49; 95% CI: 1.50-4.14) compared with men who were never classified as having overweight. Men who had persistent overweight at ages 7 and 13 and in early adulthood had an EA/GCA risk that was 3.2 times higher (HR = 3.18; 95% CI: 1.57-6.44). However, there was little evidence of increased EA/GCA risk for men with overweight during childhood and subsequent remittance by early adulthood. CONCLUSIONS: Persistent overweight in early life is associated with increased EA/GCA risk, which declines if body weight is reduced.


Assuntos
Adenocarcinoma/etiologia , Cárdia/fisiopatologia , Neoplasias Esofágicas/etiologia , Sobrepeso/complicações , Neoplasias Gástricas/etiologia , Adenocarcinoma/fisiopatologia , Adolescente , Adulto , Criança , Neoplasias Esofágicas/fisiopatologia , Feminino , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco , Neoplasias Gástricas/fisiopatologia , Adulto Jovem
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