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1.
Int J Cancer ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31593602

RESUMO

Elevated cutaneous nevus number has been linked to longer telomeres. Recently, a large systematic Mendelian randomization study identified a significant positive association between telomere length and risk of cancer. Here, we hypothesized that higher nevus count, as a phenotypic marker of longer telomere, may be associated with increased risk of internal cancer, and prospectively examined the association between nevus count and total as well as site-specific cancer risk among participants in the Nurses' Health Study (NHS, 1986-2012) and the Nurses' Health Study 2 (NHS2, 1989-2013) using Cox proportional hazards models. During 3,900,264 person-years of follow-up, we documented a total of 23,004 internal cancer cases (15,484 in the NHS and 7,520 in the NHS2). Compared to participants who had no nevi, the multivariate hazard ratios of total cancer (excluding skin cancer) were 1.06 (95% confidence interval [CI], 1.03-1.09) for women with 1-5 nevi, 1.08 (95% CI, 1.03-1.15) for those who had 6-14 nevi, and 1.19 (95% CI, 1.05-1.35) for those with 15 or more nevi (p trend <0.0001). Moreover, because nevus count has been associated with risk of breast cancer previously, we conducted a secondary analysis by excluding breast cancer from the outcomes of interest. The results were very similar to those of our primary analysis. For individual cancer, most of the associations with nevus count were positive but not statistically significant. In conclusion, we identified the number of cutaneous nevi as a phenotypic marker associated with internal cancer risk, which may be explained by telomere biology. This article is protected by copyright. All rights reserved.

2.
Eur J Epidemiol ; 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31559554

RESUMO

Background Statins have previously been shown to have protective effects for other cancers, but no prospective studies of statin use and glioma have been conducted. Methods We evaluated the association between statin use and risk of glioma in the female Nurses' Health Study (NHS, n = 114,419) and Nurses' Health Study II (NHSII, n = 115,813) and the male Health Professionals Follow-up Study (HPFS, n = 50,223). Glioma cases were confirmed by medical record review. Age and multivariable-adjusted hazard ratios of glioma by statin use were estimated using Cox proportional hazards models. Results In 4,430,700 person-years of follow-up, we confirmed 483 incident cases of glioma. Compared with never-users, ever statin use was associated with borderline increased risk of glioma in the combined cohorts (age-adjusted HR = 1.23, 95% CI 0.99-1.54), as was longer duration of statin use (HR = 1.48, 95% CI 1.08-2.03 comparing > 8 years of use to never use, p-trend = 0.01). We also observed a significant inverse association between hyperlipidemia and glioma in multivariable models (HR = 0.74, 95% CI 0.59-0.93 in combined cohorts), which was attenuated in lagged analyses. Compared to never use, in multivariable-adjusted models, ever statin use (HR = 1.43, 95% CI 1.10-1.86) and statin use duration (HR = 1.72, 95% CI 1.21-2.45, for > 8 years of use, p-trend = 0.003) were each significantly associated with increased glioma risk. Conclusion In contrast to case-control studies reporting inverse associations, we found borderline increased risk of glioma with statin use. Results were strengthened after adjustment for cardiovascular risk factors due to an unexpected inverse association between hyperlipidemia and glioma risk. Further studies of statin use, hyperlipidemia, and glioma risk are warranted.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31427306

RESUMO

BACKGROUND: Leukocyte telomere length has been associated with risk of subsequent pancreatic cancer. Few prospective studies have evaluated the association of prediagnostic leukocyte telomere length with pancreatic cancer survival. METHODS: We prospectively examined the association of prediagnostic leukocyte telomere length with overall survival (OS) time among 423 participants diagnosed with pancreatic adenocarcinoma between 1984 and 2008 within the Health Professionals Follow-up Study, Nurses' Health Study, Physicians' Health Study, and Women's Health Initiative. We measured prediagnostic leukocyte telomere length in banked blood samples using quantitative PCR. Cox proportional hazards models were used to estimate HRs for OS with adjustment for potential confounders. We also evaluated 10 SNPs at the telomerase reverse transcriptase locus. RESULTS: Shorter prediagnostic leukocyte telomere length was associated with reduced OS among patients with pancreatic cancer (P trend = 0.04). The multivariable-adjusted HR for OS comparing the lowest with highest quintiles of leukocyte telomere length was 1.39 (95% confidence interval, 1.01-1.93), corresponding to a 3-month difference in median OS time. In an analysis excluding cases with blood collected within 2 years of cancer diagnosis, the association was moderately stronger (HR, 1.55; 95% confidence interval, 1.09-2.21; comparing the lowest with highest quintiles; P trend = 0.01). No prognostic association or effect modification for the prognostic association of prediagnostic leukocyte telomere length was noted in relation to the studied SNPs. CONCLUSIONS: Prediagnostic leukocyte telomere length was associated with pancreatic cancer survival. IMPACT: Prediagnostic leukocyte telomere length can be a prognostic biomarker in pancreatic cancer.

4.
Int J Cancer ; 2019 Jul 05.
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.

5.
Int J Cancer ; 2019 Jul 15.
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.

6.
Cancer Epidemiol Biomarkers Prev ; 28(9): 1534-1543, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31217167

RESUMO

BACKGROUND: Few epidemiologic studies have investigated trace element exposure and skin cancer risk. METHODS: Toenail levels of mercury, selenium, chromium, iron, and zinc were measured from 6,708 women in the Nurses' Health Study (1984-2012) and 3,730 men in the Health Professionals Follow-up Study (1986-2012) with data from prior nested case-control studies. Participants were free of skin cancer at toenail collection and followed for incident basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. Cox proportional hazards models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) of skin cancer associated with the elements in each study. We calculated pooled multivariable HRs using a fixed-effects model. During 26 to 28 years of follow-up, 2,433 BCC, 334 SCC, and 130 melanoma cases were documented. RESULTS: Higher toenail mercury levels were associated with risk of BCC [pooled HR for top vs. bottom quintiles = 1.34 (95% CI, 1.18-1.52), P trend < 0.0001]. Similar direct associations were found with risks of SCC [pooled HR for top vs. bottom quartiles = 1.41 (95% CI, 1.03-1.94), P trend = 0.04] and melanoma [pooled HR for top vs. bottom quartiles = 1.88 (95% CI, 1.12-3.16), P trend = 0.02]. Chromium was positively associated with BCC in women only. No associations were found between other metals and skin cancer risk. CONCLUSIONS: Our prospective data found that increased toenail mercury concentrations were associated with increased skin cancer risk. IMPACT: If our novel findings are confirmed, mercury may play a role in skin carcinogenesis.

7.
Cancer ; 125(19): 3390-3400, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31206646

RESUMO

BACKGROUND: Multiple studies have reported higher rates of glioma in areas with higher socioeconomic status (SES) but to the authors' knowledge have not stratified by other factors, including race/ethnicity or urban versus rural location. METHODS: The authors identified the average annual age-adjusted incidence rates and calculated hazard ratios for death for gliomas of various subtypes, stratified by a county-level index for SES, race/ethnicity, US region, and rural versus urban status. RESULTS: Rates of glioma were highest in counties with higher SES (rate ratio, 1.18; 95% CI, 1.15-1.22 comparing the highest with the lowest quintiles [P < .001]). Stratified by race/ethnicity, higher rates in high SES counties persisted for white non-Hispanic individuals. Stratified by rural versus urban status, differences in incidence by SES were more pronounced among urban counties. Survival was higher for residents of high SES counties after adjustment for age and extent of surgical resection (hazard ratio, 0.82; 95% CI, 0.76-0.87 comparing the highest with the lowest quintile of SES [P < .001]). Survival was higher among white Hispanic, black, and Asian/Pacific Islander individuals compared with white non-Hispanic individuals, after adjustment for age, SES, and extent of surgical resection, and when restricted to those individuals with glioblastoma who received radiation and chemotherapy. CONCLUSIONS: The incidence of glioma was higher in US counties of high compared with low SES. These differences were most pronounced among white non-Hispanic individuals and white Hispanic individuals residing in urban areas. Better survival was observed in high SES counties, even when adjusting for extent of surgical resection, and when restricted to those who received radiation and chemotherapy for glioblastoma. Differences in incidence and survival were associated with SES and race, rather than rural versus urban status.

8.
Diabetes Care ; 42(7): 1162-1169, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31076421

RESUMO

OBJECTIVE: To compare the postprandial and overnight glycemic response using a novel green aquatic plant thought to provide a dietary source for high-quality protein, with an iso-carbohydrate/protein/caloric dairy shake. RESEARCH DESIGN AND METHODS: This is a randomized controlled crossover trial among 20 abdominally obese participants (age 51.4 years; fasting plasma glucose 110.9 mg/dL), who were allocated to replace dinner with either, first, a green shake containing Wolffia globosa duckweed (Mankai: specific-strain) or an iso-carbohydrate/protein/calorie yogurt shake. A 2-week flash glucose-monitoring system was used to assess postmeal glucose dynamics (6 net administration days; 97 observation days in total). We further obtained from each participant dietary/daily activity/satiety scale/sleep logs. Participants were recruited from the green-Mediterranean diet arm of the 18-month Dietary Intervention Randomized Controlled Trial-Polyphenols Unprocessed (DIRECT-PLUS) study. RESULTS: Wolffia globosa Mankai elicited a lower postprandial glucose peak compared with yogurt (∆peak = 13.4 ± 9.2 vs. 19.3 ± 15.1 mg/dL; P = 0.044), which occurred later (77.5 ± 29.2 vs. 59.2 ± 28.4 min; P = 0.037) and returned faster to baseline glucose levels (135.8 ± 53.1 vs. 197.5 ± 70.2 min; P = 0.012). The mean post-net incremental area under the curve (netAUC) was lower with Wolffia globosa up to 60 and 180 min (netAUC 60 min: 185.1 ± 340.1 vs. 441.4 ± 336.5 mg/dL/min, P = 0.005; netAUC 180 min: 707.9 ± 1,428.5 vs. 1,576.6 ± 1,810.1 mg/dL/min, P = 0.037). A Wolffia globosa-based shake replacing dinner resulted in lower next-morning fasting glucose levels (83.2 ± 0.8 vs. 86.6 ± 13 mg/dL; P = 0.041). Overall, postprandial glucose levels from the shake administration until the next morning were lower in the Wolffia globosa Mankai green shake compared with the yogurt shake (P < 0.001). Overnight sleep duration was similar (378.2 ± 22.4 vs. 375.9 ± 28.4 min; P = 0.72), and satiety rank was slightly higher for the Wolffia globosa shake compared with the yogurt shake (7.5 vs. 6.5; P = 0.035). CONCLUSIONS: Wolffia globosa Mankai duckweed may serve as an emerging alternative plant protein source with potential beneficial postprandial glycemic effects.

9.
J Hepatol ; 71(2): 379-388, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31075323

RESUMO

BACKGROUND & AIM: It is unclear if a reduction in hepatic fat content (HFC) is a major mediator of the cardiometabolic benefit of lifestyle intervention, and whether it has prognostic significance beyond the loss of visceral adipose tissue (VAT). In the present sub-study, we hypothesized that HFC loss in response to dietary interventions induces specific beneficial effects independently of VAT changes. METHODS: In an 18-month weight-loss trial, 278 participants with abdominal obesity/dyslipidemia were randomized to low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC + 28 g walnuts/day) diets with/without moderate physical activity. HFC and abdominal fat-depots were measured using magnetic resonance imaging at baseline, after 6 (sub-study, n = 158) and 18 months. RESULTS: Of 278 participants (mean HFC 10.2% [range: 0.01%-50.4%]), the retention rate was 86.3%. The %HFC substantially decreased after 6 months (-6.6% absolute units [-41% relatively]) and 18 months (-4.0% absolute units [-29% relatively]; p <0.001 vs. baseline). Reductions of HFC were associated with decreases in VAT beyond weight loss. After controlling for VAT loss, decreased %HFC remained independently associated with reductions in serum gamma glutamyltransferase and alanine aminotransferase, circulating chemerin, and glycated hemoglobin (p <0.05). While the reduction in HFC was similar between physical activity groups, MED/LC induced a greater %HFC decrease (p = 0.036) and greater improvements in cardiometabolic risk parameters (p <0.05) than the LF diet, even after controlling for VAT changes. Yet, the greater improvements in cardiometabolic risk parameters induced by MED/LC were all markedly attenuated when controlling for HFC changes. CONCLUSIONS: %HFC is substantially reduced by diet-induced moderate weight loss and is more effectively reduced by the MED/LC diet than the LF diet, independently of VAT changes. The beneficial effects of the MED/LC diet on specific cardiometabolic parameters appear to be mediated more by decreases in %HFC than VAT loss. LAY SUMMARY: High hepatic fat content is associated with metabolic syndrome, type 2 diabetes mellitus, and coronary heart disease. In the CENTRAL 18-month intervention trial, a Mediterranean/low-carbohydrate diet induced a greater decrease in hepatic fat content than a low-fat diet, conferring beneficial health effects that were beyond the favorable effects of visceral fat loss. ClinicalTrials.gov Identifier: NCT01530724.

10.
J Nutr ; 149(6): 1065-1074, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31049577

RESUMO

BACKGROUND: The preventable premature mortality achievable by improvement in dietary quality at a global level is unclear. OBJECTIVE: The aim of this study was to assess dietary quality globally, and to quantify the potential global impact of improving dietary quality on population health. METHODS: We applied the Alternate Healthy Eating Index (AHEI, potential range 0-100) to a global dietary database to assess dietary quality among adults in 190 countries/territories. The relation of AHEI score to risks of major chronic disease was estimated from 2 large cohorts of men and women for whom many repeated dietary assessments during up to 30 years were available. We calculated the preventable premature deaths achievable by shifting from current national diets to a reference healthy diet. RESULTS: The global mean AHEI score in 2017 was 49.5 for males and 50.5 for females. Large differences between current and target intakes existed for whole grains, sodium, long-chain n-3 polyunsaturated fats, polyunsaturated fats, and fruits. From 1990 to 2017, the global mean AHEI score increased modestly from 45.4 to 50.0. Diet quality varied substantially across the world. Coastal Mediterranean nations, the Caribbean region, and Eastern Asia (except China and Mongolia) had a higher AHEI score, whereas Central Asia, the South Pacific, and Eastern and Northern Europe had a lower score. An improvement in dietary quality from the current global diet to the reference healthy diet could prevent >11 million premature deaths, ∼24% of total deaths in 2017. These included 1.6 million cancer deaths, 3.9 million coronary artery disease deaths, 1.0 million stroke deaths, 1.7 million respiratory disease deaths, 0.4 million neurodegenerative disease deaths, 0.5 million kidney disease deaths, 0.6 million diabetes deaths, and 1.2 million digestive disease deaths. CONCLUSIONS: Global dietary quality is slowly improving, but remains far from optimal and varies across countries. Improvements in dietary quality have the potential to reduce mortality rates substantially.

11.
J Clin Oncol ; 37(17): 1499-1511, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31026211

RESUMO

PURPOSE: It is unknown whether alcohol intake is associated with the risk of lethal (metastatic or fatal) prostate cancer. We examine (1) whether alcohol intake among men at risk of prostate cancer is associated with diagnosis of lethal prostate cancer and (2) whether intake among men with nonmetastatic prostate cancer is associated with metastasis or death. METHODS: This prospective cohort study uses the Health Professionals Follow-Up Study (1986 to 2012). Our analysis of alcohol intake among men at risk of prostate cancer included 47,568 cancer-free men. Our analysis of alcohol intake among men with prostate cancer was restricted to 5,182 men diagnosed with nonmetastatic prostate cancer during follow-up. We examine the association of total alcohol, red and white wine, beer, and liquor with lethal prostate cancer and death. Multivariate Cox proportional hazards regression estimated hazard ratios (HRs) and 95% CIs. RESULTS: Alcohol drinkers had a lower risk of lethal prostate cancer (any v none: HR, 0.84 [95% CI, 0.71 to 0.99]) without a dose-response relationship. Total alcohol intake among patients with prostate cancer was not associated with progression to lethal prostate cancer (any v none: HR, 0.99 [95% CI, 0.57 to 1.72]), whereas moderate red wine intake was associated with a lower risk (any v none: HR, 0.50 [95% CI, 0.29 to 0.86]; P trend = .05). Compared with none, 15 to 30 g/d of total alcohol after prostate cancer diagnosis was associated with a lower risk of death (HR, 0.71 [95% CI, 0.50 to 1.00]), as was red wine (any v none: HR, 0.74 [95% CI, 0.57 to 0.97]; P trend = .007). CONCLUSION: Cancer-free men who consumed alcohol had a slightly lower risk of lethal prostate cancer compared with abstainers. Among men with prostate cancer, red wine was associated with a lower risk of progression to lethal disease. These observed associations merit additional study but provide assurance that moderate alcohol consumption is safe for patients with prostate cancer.

12.
Eur Urol Oncol ; 2(2): 126-134, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31017087

RESUMO

BACKGROUND: Aspirin use probably protects against some malignancies but its effects on lethal prostate cancer (PC) are unclear. OBJECTIVE: To investigate the association between regular aspirin use and lethal PC. DESIGN, SETTING, AND PARTICIPANTS: Participants were aged 40-75 yr at baseline in 1986 and have been followed with biennial questionnaires. The risk analysis includes 49 409 men. The survival analysis includes 5980 PC patients without metastatic disease at diagnosis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used Cox proportional hazards regression to examine the association between current, past, or never regular aspirin use (≥2 d/wk) in relation to lethal (metastatic or fatal) PC. We also examined years of use among current users and years since stopping among past users. In the risk analysis, aspirin was updated throughout follow-up. In the survival analysis, aspirin use after diagnosis was assessed. RESULTS AND LIMITATIONS: Some 29% of participants used aspirin regularly at baseline, which increased to 60% by 2010. In the risk analysis, 804 men were diagnosed with lethal PC. Current regular aspirin was associated with a lower risk of lethal prostate cancer (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.66-0.96) compared to never users. In the survival analysis, 451 of the men diagnosed with nonmetastatic PC later developed lethal disease. Current postdiagnostic aspirin was associated with a lower risk of lethal PC (HR 0.80, 95% CI 0.64-1.00) and overall mortality (HR 0.79, 95% CI 0.69-0.90). When restricted to highly screened men, the risk analysis associations were stronger and survival analysis associations remained statistically significant. Reverse causation and residual confounding remain concerns, as demonstrated by the attenuated results in sensitivity analyses. CONCLUSIONS: Regular aspirin use was associated with a lower risk of lethal PC. Postdiagnostic use was associated with better survival after diagnosis. PATIENT SUMMARY: We found that it may be advisable for prostate cancer patients to take aspirin to improve their survival for both prostate cancer mortality and other mortality outcomes.

13.
Circulation ; 139(15): 1828-1845, 2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30958719

RESUMO

BACKGROUND: Findings among randomized controlled trials evaluating the effect of red meat on cardiovascular disease risk factors are inconsistent. We provide an updated meta-analysis of randomized controlled trials on red meat and cardiovascular risk factors and determine whether the relationship depends on the composition of the comparison diet, hypothesizing that plant sources would be relatively beneficial. METHODS: We conducted a systematic PubMed search of randomized controlled trials published up until July 2017 comparing diets with red meat with diets that replaced red meat with a variety of foods. We stratified comparison diets into high-quality plant protein sources (legumes, soy, nuts); chicken/poultry/fish; fish only; poultry only; mixed animal protein sources (including dairy); carbohydrates (low-quality refined grains and simple sugars, such as white bread, pasta, rice, cookies/biscuits); or usual diet. We performed random-effects meta-analyses comparing differences in changes of blood lipids, apolipoproteins, and blood pressure for all studies combined and stratified by specific comparison diets. RESULTS: Thirty-six studies totaling 1803 participants were included. There were no significant differences between red meat and all comparison diets combined for changes in blood concentrations of total, low-density lipoprotein, or high-density lipoprotein cholesterol, apolipoproteins A1 and B, or blood pressure. Relative to the comparison diets combined, red meat resulted in lesser decreases in triglycerides (weighted mean difference [WMD], 0.065 mmol/L; 95% CI, 0.000-0.129; P for heterogeneity <0.01). When analyzed by specific comparison diets, relative to high-quality plant protein sources, red meat yielded lesser decreases in total cholesterol (WMD, 0.264 mmol/L; 95% CI, 0.144-0.383; P<0.001) and low-density lipoprotein (WMD, 0.198 mmol/L; 95% CI, 0.065-0.330; P=0.003). In comparison with fish, red meat yielded greater decreases in low-density lipoprotein (WMD, -0.173 mmol/L; 95% CI, -0.260 to -0.086; P<0.001) and high-density lipoprotein (WMD, -0.065 mmol/L; 95% CI, -0.109 to -0.020; P=0.004). In comparison with carbohydrates, red meat yielded greater decreases in triglycerides (WMD, -0.181 mmol/L; 95% CI, -0.349 to -0.013). CONCLUSIONS: Inconsistencies regarding the effects of red meat on cardiovascular disease risk factors are attributable, in part, to the composition of the comparison diet. Substituting red meat with high-quality plant protein sources, but not with fish or low-quality carbohydrates, leads to more favorable changes in blood lipids and lipoproteins.

14.
J Nutr ; 149(6): 1004-1011, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30915471

RESUMO

BACKGROUND: Decreased dietary meat may deplete iron stores, as plant-derived iron bioavailability is typically limited. OBJECTIVES: We explored the effect of a low-meat Mediterranean (green-MED) diet, supplemented with Wolffia globosa duckweed (Mankai: rich in protein and iron) as a food source for humans, on iron status. We further examined the iron bioavailability of Mankai in rats. METHODS: Two hundred and ninety-four abdominally obese/dyslipidemic [mean age = 51.1 y; body mass index (kg/m2) = 31.3; 88% men] nonanemic participants were randomly assigned to physical activity (PA), PA + MED diet, or PA + green-MED diet. Both isocaloric MED groups consumed 28 g walnuts/d and the low-meat green-MED group further consumed green tea (800 mL/d) and Mankai (100 g green shake/d). In a complementary animal experiment, after 44 d of an iron deficiency anemia-inducing diet, 50 female rats (age = 3 wk; Sprague Dawley strain) were randomly assigned into: iron-deficient diet (vehicle), or vehicle + iso-iron: ferrous gluconate (FG) 14, Mankai 50, and Mankai 80 versions (1.7 mg · kg-1 · d-1 elemental iron), or FG9.5 and Mankai 50-C version (1.15 mg · kg-1 · d-1 elemental iron). The specific primary aim for both studies was changes in iron homeostasis parameters. RESULTS: After 6 mo of intervention, iron status trajectory did not differ between the PA and PA + MED groups. Hemoglobin modestly increased in the PA + green-MED group (0.23 g/dL) compared with PA (-0.1 g/dL; P < 0.001) and PA + MED (-0.1 g/dL; P < 0.001). Serum iron and serum transferrin saturation increased in the PA + green-MED group compared with the PA group (8.21 µg/dL compared with -5.23 µg/dL and 2.39% compared with -1.15%, respectively; P < 0.05 for both comparisons), as did folic acid (P = 0.011). In rats, hemoglobin decreased from 15.7 to 9.4 mg/dL after 44 d of diet-induced anemia. After depletion treatment, the vehicle-treated group had a further decrease of 1.3 mg/dL, whereas hemoglobin concentrations in both FG and Mankai iso-iron treatments similarly rebounded (FG14: +10.8 mg/dL, Mankai 50: +6.4 mg/dL, Mankai 80: +7.3 mg/dL; FG9.5: +5.1 mg/dL, Mankai 50-C: +7.1 mg/dL; P < 0.05 for all vs. the vehicle group). CONCLUSIONS: In humans, a green-MED low-meat diet does not impair iron homeostasis. In rats, iron derived from Mankai (a green-plant protein source) is bioavailable and efficient in reversal of anemia. This trial was registered at clinicaltrials.gov as NCT03020186.

15.
Br J Cancer ; 120(8): 848-854, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30867564

RESUMO

BACKGROUND: Individuals with a family history of cancer may be at increased risk of pancreatic cancer. Ashkenazi Jewish (AJ) individuals carry increased risk for pancreatic cancer and other cancer types. METHODS: We examined the association between family history of cancer, AJ heritage, and incident pancreatic cancer in 49 410 male participants of the prospective Health Professionals Follow-up Study. Hazard ratios (HRs) were estimated using multivariable-adjusted Cox proportional hazards models. RESULTS: During 1.1 million person-years (1986-2016), 452 participants developed pancreatic cancer. Increased risk of pancreatic cancer was observed in individuals with a family history of pancreatic (HR, 2.79; 95% confidence interval [CI], 1.28-6.07) or breast cancer (HR, 1.40; 95% CI, 1.01-1.94). There was a trend towards higher risk of pancreatic cancer in relation to a family history of colorectal cancer (HR, 1.21; 95% CI, 0.95-1.55) or AJ heritage (HR, 1.29; 95% CI, 0.94-1.77). The risk was highly elevated among AJ men with a family history of breast or colorectal cancer (HR, 2.61 [95% CI, 1.41-4.82] and 1.92 [95% CI, 1.05-3.49], respectively). CONCLUSION: Family history of pancreatic cancer was associated with increased risk of this malignancy. Family history of breast or colorectal cancer was associated with the increased risk among AJ men.

16.
Cancer Causes Control ; 30(4): 333-342, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30805814

RESUMO

PURPOSE: Our main aim was to explore whether pre-diagnostic circulating levels of 25-hydroxyvitamin D (25(OH)D) among older individuals with cancer were associated with overall and cancer-specific survival after diagnosis. DESIGN: We used data from the Reykjavik-AGES Study on participants (n = 4,619) without cancer at entry, when blood samples were taken for 25(OH)D standardized measurements. The association with cancer risk, all-cause- and cancer-specific mortality was assessed among those later diagnosed with cancer, comparing four 25(OH)D categories, using 50-69.9 nmol/L as the reference category. RESULTS: Cancer was diagnosed in 919 participants on average 8.3 years after blood draw. No association was observed between the reference group and other 25(OH)D groups and total cancer incidence. Mean age at diagnosis was 80.9 (± 5.7) years. Of those diagnosed, 552 died during follow-up, 67% from cancer. Low pre-diagnostic levels of 25(OH)D < 30 nmol/L were significantly associated with increased total mortality (HR: 1.39, 95% CI 1.03, 1.88) and non-significantly with cancer-specific mortality (HR: 1.33, 95% CI 0.93, 1.90). Among patients surviving more than 2 years after diagnosis, higher pre-diagnostic 25(OH)D levels (≥ 70 nmol/L) were associated with lower risk of overall (HR: 0.68, 95% CI 0.46, 0.99) and cancer-specific mortality (HR: 0.47, 95% CI 0.26, 0.99). CONCLUSIONS: Among elderly cancer patients, low pre-diagnostic serum 25(OH)D levels (< 30 nmol/L) were associated with increased overall mortality.


Assuntos
Neoplasias/patologia , Vitamina D/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Incidência , Masculino , Neoplasias/sangue , Risco , Sobrevida , Vitamina D/sangue , Deficiência de Vitamina D/sangue
17.
J Am Acad Dermatol ; 80(5): 1284-1291, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30639880

RESUMO

BACKGROUND: It was unclear whether an increased number of common nevi (moles) predicts melanoma death. OBJECTIVE: We prospectively examined the association between number of common nevi and risk of melanoma death. METHODS: Our study used data from the Nurses' Health Study (n = 77,288 women) and Health Professionals Follow-up Study (n = 32,455 men). In 1986, participants were asked about the number of moles they had with a ≥3-mm diameter on the upper extremity, and we stratified their answers into 3 categories (none, 1-2, or ≥3) on the basis of data distribution. RESULTS: During follow-up (1986-2012), 2452 melanoma cases were pathologically confirmed; among these, we identified 196 deaths due to melanoma. Increased number of nevi was associated with melanoma death; the hazard ratio (HR) for ≥3 nevi compared with no nevi was 2.49 (95% confidence interval [CI] 1.50-4.12) for women and 3.97 (95% CI 2.54-6.22) for men. Among melanoma cases, increased number of nevi was associated with melanoma death in men (≥3 nevi, HR 1.89, 95% CI 1.17-3.05) but not in women. Similarly, the number of nevi was positively associated with Breslow thickness in men only (Ptrend = .01). LIMITATIONS: This is an epidemiologic study without examination into mechanisms. CONCLUSION: Increased number of cutaneous nevi was significantly associated with melanoma death. High nevus count might serve as an independent prognostic factor to predict the risk of melanoma death particularly among male melanoma patients.


Assuntos
Melanoma/mortalidade , Melanoma/patologia , Nevo/patologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Nevo/epidemiologia , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Neoplasias Cutâneas/epidemiologia , Carga Tumoral , Estados Unidos/epidemiologia
18.
BMJ ; 364: k4981, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30606716

RESUMO

OBJECTIVES: To conduct a comprehensive analysis of prospectively measured circulating high sensitivity C reactive protein (hsCRP) concentration and risk of lung cancer overall, by smoking status (never, former, and current smokers), and histological sub-type. DESIGN: Nested case-control study. SETTING: 20 population based cohort studies in Asia, Europe, Australia, and the United States. PARTICIPANTS: 5299 patients with incident lung cancer, with individually incidence density matched controls. EXPOSURE: Circulating hsCRP concentrations in prediagnostic serum or plasma samples. MAIN OUTCOME MEASURE: Incident lung cancer diagnosis. RESULTS: A positive association between circulating hsCRP concentration and the risk of lung cancer for current (odds ratio associated with a doubling in hsCRP concentration 1.09, 95% confidence interval 1.05 to 1.13) and former smokers (1.09, 1.04 to 1.14) was observed, but not for never smokers (P<0.01 for interaction). This association was strong and consistent across all histological subtypes, except for adenocarcinoma, which was not strongly associated with hsCRP concentration regardless of smoking status (odds ratio for adenocarcinoma overall 0.97, 95% confidence interval 0.94 to 1.01). The association between circulating hsCRP concentration and the risk of lung cancer was strongest in the first two years of follow-up for former and current smokers. Including hsCRP concentration in a risk model, in addition to smoking based variables, did not improve risk discrimination overall, but slightly improved discrimination for cancers diagnosed in the first two years of follow-up. CONCLUSIONS: Former and current smokers with higher circulating hsCRP concentrations had a higher risk of lung cancer overall. Circulating hsCRP concentration was not associated with the risk of lung adenocarcinoma. Circulating hsCRP concentration could be a prediagnostic marker of lung cancer rather than a causal risk factor.


Assuntos
Proteína C-Reativa/metabolismo , Carcinoma de Células Grandes/sangue , Carcinoma de Células Pequenas/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Pulmonares/sangue , Fumar/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Grandes/epidemiologia , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Estudos de Casos e Controles , Ex-Fumantes/estatística & dados numéricos , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , não Fumantes/estatística & dados numéricos , Razão de Chances , Estudos Prospectivos , Medição de Risco , Sensibilidade e Especificidade , Fumantes/estatística & dados numéricos , Fumar/epidemiologia , Adulto Jovem
19.
Int J Cancer ; 2018 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-30499135

RESUMO

Vitamin B supplementation can have side effects for human health, including cancer risk. We aimed to elucidate the role of vitamin B12 in lung cancer aetiology via direct measurements of pre-diagnostic circulating vitamin B12 concentrations in a nested case-control study, complemented with a Mendelian randomization (MR) approach in an independent case-control sample. We used pre-diagnostic biomarker data from 5,183 case-control pairs nested within 20 prospective cohorts, and genetic data from 29,266 cases and 56,450 controls. Exposures included directly measured circulating vitamin B12 in pre-diagnostic blood samples from the nested case-control study, and 8 single nucleotide polymorphisms associated with vitamin B12 concentrations in the MR study. Our main outcome of interest was increased risk for lung cancer, overall and by histological subtype, per increase in circulating vitamin B12 concentrations. We found circulating vitamin B12 to be positively associated with overall lung cancer risk in a dose response fashion (odds ratio for a doubling in B12 [ORlog2B12 ] = 1.15, 95% confidence interval (95%CI) = 1.06-1.25). The MR analysis based on 8 genetic variants also indicated that genetically determined higher vitamin B12 concentrations were positively associated with overall lung cancer risk (OR per 150 pmol/L standard deviation increase in B12 [ORSD ]= 1.08, 95%CI= 1.00-1.16). Considering the consistency of these two independent and complementary analyses, these findings support the hypothesis that high vitamin B12 status increases the risk of lung cancer. This article is protected by copyright. All rights reserved.

20.
Menopause ; 26(6): 603-610, 2018 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-30562320

RESUMO

OBJECTIVE: To examine the associations between vaginal estrogen use and multiple health outcomes including cardiovascular disease (total myocardial infarction, stroke, and pulmonary embolism/deep vein thrombosis), cancer (total invasive, breast, endometrial, ovarian, and colorectal cancer), and hip fracture. METHODS: We included postmenopausal women from the Nurses' Health Study (1982-2012) who were not current users of systemic hormone therapy at the start of the study or during follow-up. Vaginal estrogen use was self-reported on the biennial questionnaires. Information on incident health outcomes were self-reported and confirmed by medical records. We used Cox proportional hazards regression to model the multivariable adjusted hazard ratios and the 95% confidence intervals for vaginal estrogen use and multiple health outcomes. RESULTS: Over 18 years of follow-up, after adjusting for covariates, risks for cardiovascular disease, cancer, and hip fracture were not different between users and nonusers of vaginal estrogen. No statistically significant increase in risk of any health outcome was observed with vaginal estrogen use. In sensitivity analyses, when we examined associations by hysterectomy status, the stratified results were generally similar to those for the total cohort. CONCLUSIONS: Vaginal estrogen use was not associated with a higher risk of cardiovascular disease or cancer. Our findings lend support to the safety of vaginal estrogen use, a highly effective treatment for genitourinary syndrome of menopause.

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