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1.
Int J Epidemiol ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33624757

RESUMO

BACKGROUND: Coffee consumption has been associated with a reduced risk of some cancers, but the evidence for renal cell carcinoma (RCC) is inconclusive. We investigated the relationship between coffee and RCC within a large cohort. METHODS: Coffee intake was assessed at baseline in the National Institutes of Health-American Association of Retired Persons Diet and Health Study. Among 420 118 participants eligible for analysis, 2674 incident cases were identified. We fitted Cox-regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for coffee consumption vs non-drinkers. RESULTS: We observed HRs of 0.94 (95% CI 0.81, 1.09), 0.94 (0.81, 1.09), 0.80 (0.70, 0.92) and 0.77 (0.66, 0.90) for usual coffee intake of <1, 1, 2-3 and ≥4 cups/day, respectively (Ptrend = 0.00003). This relationship was observed among never-smokers (≥4 cups/day: HR 0.62, 95% CI 0.46, 0.83; Ptrend = 0.000003) but not ever-smokers (HR 0.85, 95% CI 0.70, 1.05; Ptrend = 0.35; Pinteraction = 0.0009) and remained in analyses restricted to cases diagnosed >10 years after baseline (HR 0.65, 95% CI 0.51, 0.82; Ptrend = 0.0005). Associations were similar between subgroups who drank predominately caffeinated or decaffeinated coffee (Pinteraction = 0.74). CONCLUSION: In this investigation of coffee and RCC, to our knowledge the largest to date, we observed a 20% reduced risk for intake of ≥2 cups/day vs not drinking. Our findings add RCC to the growing list of cancers for which coffee consumption may be protective.

2.
Int J Cancer ; 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33460452

RESUMO

The gut microbiota may play a role in breast cancer etiology by regulating hormonal, metabolic, and immunologic pathways. We investigated associations of fecal bacteria with breast cancer and non-malignant breast disease in a case-control study conducted in Ghana, a country with rising breast cancer incidence and mortality. To do this, we sequenced the V4 region of the 16S rRNA gene to characterize bacteria in fecal samples collected at the time of breast biopsy (N = 379 breast cancer cases, N = 102 non-malignant breast disease cases, N = 414 population-based controls). We estimated associations of alpha diversity (observed amplicon sequence variants [ASVs], Shannon index, and Faith's phylogenetic diversity), beta diversity (Bray Curtis and unweighted/weighted UniFrac distance), and presence and relative abundance of select taxa with breast cancer and non-malignant breast disease using multivariable unconditional polytomous logistic regression. All alpha diversity metrics were strongly, inversely associated with odds of breast cancer and for those in the highest relative to lowest tertile of observed ASVs, the odds ratio (95% confidence interval) was 0.21 (0.13-0.36; Ptrend  < 0.001). Alpha diversity associations were similar for non-malignant breast disease and breast cancer grade/molecular subtype. All beta diversity distance matrices and multiple taxa with possible estrogen-conjugating and immune-related functions were strongly associated with breast cancer (all P's < 0.001). There were no statistically significant differences between breast cancer and non-malignant breast disease cases in any microbiota metric. In conclusion, fecal bacteria characteristics were strongly and similarly associated with breast cancer and non-malignant breast disease. Our findings provide novel insight into potential microbially-mediated mechanisms of breast disease. This article is protected by copyright. All rights reserved.

3.
Int J Cancer ; 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33326609

RESUMO

Associations of coffee and tea consumption with lung cancer risk have been inconsistent, and most lung cancer cases investigated were smokers. Included in this study were over 1.1 million participants from 17 prospective cohorts. Cox regression analyses were conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Potential effect modifications by sex, smoking, race, cancer subtype and coffee type were assessed. After a median 8.6 years of follow-up, 20 280 incident lung cancer cases were identified. Compared with noncoffee and nontea consumption, HRs (95% CIs) associated with exclusive coffee drinkers (≥2 cups/d) among current, former and never smokers were 1.30 (1.15-1.47), 1.49 (1.27-1.74) and 1.35 (1.15-1.58), respectively. Corresponding HRs for exclusive tea drinkers (≥2 cups/d) were 1.16 (1.02-1.32), 1.10 (0.92-1.32) and 1.37 (1.17-1.61). In general, the coffee and tea associations did not differ significantly by sex, race or histologic subtype. Our findings suggest that higher consumption of coffee or tea is associated with increased lung cancer risk. However, these findings should not be assumed to be causal because of the likelihood of residual confounding by smoking, including passive smoking, and change of coffee and tea consumption after study enrolment.

4.
Biomed Mater ; 15(6): 064102, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33226007

RESUMO

Hydrophobic drug molecules pose a significant challenge in immobilization on super-hydrophobic metallic surfaces like conventional titanium implants. Pre-coating surface modifications may yield a better platform with improved wettability for such purposes. Such modifications, as depicted in this study, were hypothesized to provide the requisite roughness to assist deposition of polymers like silk fibroin (SF) as a drug-binding matrix in addition to significant improvement in early protein adsorption, which facilitates faster cellular adhesion and proliferation. A silk-based localized drug delivery module was developed on the titanium surface and tested for its surface roughness, wettability, biocompatibility and in vitro differentiation potential of cells cultured on the coated metallic surfaces with/without external supplementation of the active metabolite of Tibolone. Conditioning of the matrix-coated implants with osteogenic as well as osteoclastogenic media supplemented with Tibolone stimulated the expression of early osteogenic gene and calcium deposition in the extracellular matrix. Significant inhibition in resorptive activity was also observed in the presence of the drug. To assess the efficacy of localized delivery of Tibolone via topographically modified titanium implants for inducing early peri-implant bone formation, osteoporosis was artificially induced in rats subjected to bilateral ovariectomy and implants were placed thereafter. Bone-specific release of Tibolone through the biomimetic matrix in osteoporotic rats collectively indicated significant improvement in peri-implant bone growth after 2 and 4 weeks (p < 0.05 compared to dummy-coated implants). These findings demonstrate for the first time that Tibolone released from SF matrix-coated implants can accelerate the biological stability of bone fixtures.

5.
Expert Rev Clin Immunol ; : 1-20, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33146561

RESUMO

Introduction: The mortality of coronavirus disease 2019 (COVID-19) is frequently driven by an injurious immune response characterized by the development of acute respiratory distress syndrome (ARDS), endotheliitis, coagulopathy, and multi-organ failure. This spectrum of hyperinflammation in COVID-19 is commonly referred to as cytokine storm syndrome (CSS). Areas covered: Medline and Google Scholar were searched up until 15th of August 2020 for relevant literature. Evidence supports a role of dysregulated immune responses in the immunopathogenesis of severe COVID-19. CSS associated with SARS-CoV-2 shows similarities to the exuberant cytokine production in some patients with viral infection (e.g.SARS-CoV-1) and may be confused with other syndromes of hyperinflammation like the cytokine release syndrome (CRS) in CAR-T cell therapy. Interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha have emerged as predictors of COVID-19 severity and in-hospital mortality. Expert opinion: Despite similarities, COVID-19-CSS appears to be distinct from HLH, MAS, and CRS, and the application of HLH diagnostic scores and criteria to COVID-19 is not supported by emerging data. While immunosuppressive therapy with glucocorticoids has shown a mortality benefit, cytokine inhibitors may hold promise as 'rescue therapies' in severe COVID-19. Given the arguably limited benefit in advanced disease, strategies to prevent the development of COVID-19-CSS are needed.

6.
Eur J Epidemiol ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33128203

RESUMO

Associations between anthropometric factors and breast cancer (BC) risk have varied inconsistently by estrogen and/or progesterone receptor (ER/PR) status. Associations between prediagnostic anthropometric factors and risk of premenopausal and postmenopausal BC overall and ER/PR status subtypes were investigated in a pooled analysis of 20 prospective cohorts, including 36,297 BC cases among 1,061,915 women, using multivariable Cox regression analyses, controlling for reproductive factors, diet and other risk factors. We estimated dose-response relationships and tested for nonlinear associations using restricted cubic splines. Height showed positive, linear associations for premenopausal and postmenopausal BC risk (6-7% RR increase per 5 cm increment), with stronger associations for receptor-positive subtypes. Body mass index (BMI) at cohort baseline was strongly inversely associated with premenopausal BC risk, and strongly positively-and nonlinearly-associated with postmenopausal BC (especially among women who never used hormone replacement therapy). This was primarily observed for receptor-positive subtypes. Early adult BMI (at 18-20 years) showed inverse, linear associations for premenopausal and postmenopausal BC risk (21% and 11% RR decrease per 5 kg/m2, respectively) with stronger associations for receptor-negative subtypes. Adult weight gain since 18-20 years was positively associated with postmenopausal BC risk, stronger for receptor-positive subtypes, and among women who were leaner in early adulthood. Women heavier in early adulthood generally had reduced premenopausal BC risk, independent of later weight gain. Positive associations between height, baseline (adult) BMI, adult weight gain and postmenopausal BC risk were substantially stronger for hormone receptor-positive versus negative subtypes. Premenopausal BC risk was positively associated with height, but inversely with baseline BMI and weight gain (mostly in receptor-positive subtypes). Inverse associations with early adult BMI seemed stronger in receptor-negative subtypes of premenopausal and postmenopausal BC.

7.
J Thyroid Res ; 2020: 8121395, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32963752

RESUMO

Background: Hypothyroidism is a highly prevalent and multifactorial disorder and has been implicated in the causation of dyslipidemia, dermatological diseases, atherosclerosis, and myocardial dysfunction, as well as endothelial dysfunction. The relationship between subclinical hypothyroidism and type 2 diabetes mellitus is not well established. In the present study, we attempt to find out the prevalence of subclinical hypothyroidism in type 2 diabetes mellitus and its association with glycemic control. Materials and Methods: This was an observational study in which 205 consecutive patients of T2DM visiting the outpatient department of medicine were recruited. Serum TSH, free thyroxine, free triiodothyronine, and lipid profile, as well as HbA1c assays, were done in the study participants, and they were categorized into three groups by HbA1c: <7%, 7-9%, and >9%. Results: There is a high prevalence of subclinical hypothyroidism in type 2 DM patients. Mean HbA1c in diabetics without SCH was 7.89%, whereas it was 8.33% in diabetics with SCH. This difference was statistically not significant. TSH was not found to be significantly associated with HbA1c. Conclusion: High prevalence of SCH in T2DM patients suggests that there is a need for regular follow-up to check the progression of SCH to overt hypothyroidism. High serum TSH is not a predictor of poor glycemic control.

9.
Cancer Epidemiol Biomarkers Prev ; 29(11): 2289-2299, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32855266

RESUMO

BACKGROUND: Obesity is an established risk factor for multiple cancer types. Lower microbial richness has been linked to obesity, but human studies are inconsistent, and associations of early-life body mass index (BMI) with the fecal microbiome and metabolome are unknown. METHODS: We characterized the fecal microbiome (n = 563) and metabolome (n = 340) in the Northern Finland Birth Cohort 1966 using 16S rRNA gene sequencing and untargeted metabolomics. We estimated associations of adult BMI and BMI history with microbial features and metabolites using linear regression and Spearman correlations (rs ) and computed correlations between bacterial sequence variants and metabolites overall and by BMI category. RESULTS: Microbial richness, including the number of sequence variants (rs = -0.21, P < 0.0001), decreased with increasing adult BMI but was not independently associated with BMI history. Adult BMI was associated with 56 metabolites but no bacterial genera. Significant correlations were observed between microbes in 5 bacterial phyla, including 18 bacterial genera, and metabolites in 49 of the 62 metabolic pathways evaluated. The genera with the strongest correlations with relative metabolite levels (positively and negatively) were Blautia, Oscillospira, and Ruminococcus in the Firmicutes phylum, but associations varied by adult BMI category. CONCLUSIONS: BMI is strongly related to fecal metabolite levels, and numerous associations between fecal microbial features and metabolite levels underscore the dynamic role of the gut microbiota in metabolism. IMPACT: Characterizing the associations between the fecal microbiome, the fecal metabolome, and BMI, both recent and early-life exposures, provides critical background information for future research on cancer prevention and etiology.

10.
Nutr Cancer ; : 1-8, 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32791010

RESUMO

It has been hypothesized that consumption of citrus, a group of foods particularly rich in a class of photoactive compounds known as furocoumarins, may increase the risk of malignant melanoma. However, this hypothesis has not been rigorously studied in a general sample of US men and women. This study examined the relationship between citrus intake and melanoma risk in subjects of the NIH-AARP Diet and Health Study. Among 388,467 adults, 3,894 melanoma cases were identified during a median follow-up of 15.5 years. After adjustment for relevant potential confounders, total citrus consumption was not significantly associated with melanoma risk in this cohort. Among those with higher estimated exposure to ultraviolet radiation, and among those aged 60+ years at baseline, there were significant trends toward increased melanoma risk associated with whole citrus fruit consumption (P trends = 0.01 and 0.02, respectively), but the hazard ratios of the top consumers (2+ cups per week) vs. nonconsumers were nonsignificant. Further research is needed to explore associations of citrus with melanoma risk among older adults and those with high sun exposure.

11.
JAMA Intern Med ; 180(9): 1173-1184, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32658243

RESUMO

Importance: Although emphasis has recently been placed on the importance of high-protein diets to overall health, a comprehensive analysis of long-term cause-specific mortality in association with the intake of plant protein and animal protein has not been reported. Objective: To examine the associations between overall mortality and cause-specific mortality and plant protein intake. Design, Setting, and Participants: This prospective cohort study analyzed data from 416 104 men and women in the US National Institutes of Health-AARP Diet and Health Study from 1995 to 2011. Data were analyzed from October 2018 through April 2020. Exposures: Validated baseline food frequency questionnaire dietary information, including intake of plant protein and animal protein. Main Outcomes and Measures: Hazard ratios and 16-year absolute risk differences for overall mortality and cause-specific mortality. Results: The final analytic cohort included 237 036 men (57%) and 179 068 women. Their overall median (SD) ages were 62.2 (5.4) years for men and 62.0 (5.4) years for women. Based on 6 009 748 person-years of observation, 77 614 deaths (18.7%; 49 297 men and 28 317 women) were analyzed. Adjusting for several important clinical and other risk factors, greater dietary plant protein intake was associated with reduced overall mortality in both sexes (hazard ratio per 1 SD was 0.95 [95% CI, 0.94-0.97] for men and 0.95 [95% CI, 0.93-0.96] for women; adjusted absolute risk difference per 1 SD was -0.36% [95% CI, -0.48% to -0.25%] for men and -0.33% [95% CI, -0.48% to -0.21%] for women; hazard ratio per 10 g/1000 kcal was 0.88 [95% CI, 0.84-0.91] for men and 0.86 [95% CI, 0.82-0.90] for women; adjusted absolute risk difference per 10 g/1000 kcal was -0.95% [95% CI, -1.3% to -0.68%] for men and -0.86% [95% CI, -1.3% to -0.55%] for women; all P < .001). The association between plant protein intake and overall mortality was similar across the subgroups of smoking status, diabetes, fruit consumption, vitamin supplement use, and self-reported health status. Replacement of 3% energy from animal protein with plant protein was inversely associated with overall mortality (risk decreased 10% in both men and women) and cardiovascular disease mortality (11% lower risk in men and 12% lower risk in women). In particular, the lower overall mortality was attributable primarily to substitution of plant protein for egg protein (24% lower risk in men and 21% lower risk in women) and red meat protein (13% lower risk in men and 15% lower risk in women). Conclusions and Relevance: In this large prospective cohort, higher plant protein intake was associated with small reductions in risk of overall and cardiovascular disease mortality. Our findings provide evidence that dietary modification in choice of protein sources may influence health and longevity.

12.
Pediatr Rheumatol Online J ; 18(Suppl 1): 53, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32664935

RESUMO

For reasons poorly understood, and despite the availability of biological medications blocking IL-1 and IL-6 that have markedly improved overall disease control, children with Systemic Juvenile Idiopathic Arthritis (SJIA) are now increasingly diagnosed with life-threatening chronic complications, including hepatitis and lung disease (SJIA-LD). On October 3-4, 2019, a two-day meeting, NextGen Therapies for Systemic Juvenile Idiopathic Arthritis (SJIA) & macrophage activation syndrome (MAS) organized by the Systemic JIA Foundation ( www.systemicjia.org/ ) in Washington, DC brought together scientists, clinicians, parents and FDA representatives with the objectives (1) to integrate clinical and research findings in MAS and SJIA-LD, and (2) to develop a shared understanding of this seemingly new pulmonary complication of SJIA. The current manuscript summarizes discussions and conclusions of the meeting.

13.
Am J Clin Nutr ; 112(3): 603-612, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32619213

RESUMO

BACKGROUND: Whole grains and other foods containing fiber are thought to be inversely related to colorectal cancer (CRC). However, whether these associations reflect fiber or fiber source remains unclear. OBJECTIVES: We evaluated associations of whole grain and dietary fiber intake with CRC risk in the large NIH-AARP Diet and Health Study. METHODS: We used Cox proportional hazard models to estimate HRs and 95% CIs for whole grain and dietary fiber intake and risk of CRC among 478,994 US adults, aged 50-71 y. Diet was assessed using a self-administered FFQ at baseline in 1995-1996, and 10,200 incident CRC cases occurred over 16 y and 6,464,527 person-years of follow-up. We used 24-h dietary recall data, collected on a subset of participants, to evaluate the impact of measurement error on risk estimates. RESULTS: After multivariable adjustment for potential confounders, including folate, we observed an inverse association for intake of whole grains (HRQ5 vs.Q1 : 0.84; 95% CI: 0.79, 0.90; P-trend < 0.001), but not dietary fiber (HRQ5 vs. Q1: 0.96; 95% CI: 0.88, 1.04; P-trend = 0.40), with CRC incidence. Intake of whole grains was inversely associated with all CRC cancer subsites, particularly rectal cancer (HRQ5 vs. Q1: 0.76; 95% CI: 0.67, 0.87; P-trend < 0.001). Fiber from grains, but not other sources, was associated with lower incidence of CRC (HRQ5 vs. Q1: 0.89; 95% CI: 0.83, 0.96; P-trend < 0.001), particularly distal colon (HRQ5 vs. Q1: 0.84; 95% CI: 0.73, 0.96; P-trend = 0.005) and rectal cancer (HRQ5 vs. Q1: 0.77; 95% CI: 0.66, 0.88; P-trend < 0.001). CONCLUSIONS: Dietary guidance for CRC prevention should focus on intake of whole grains as a source of fiber.


Assuntos
Neoplasias Colorretais/prevenção & controle , Dieta , Fibras na Dieta/administração & dosagem , Grãos Integrais , Idoso , Estudos de Coortes , Comportamento Alimentar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Br J Cancer ; 123(2): 316-324, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32376888

RESUMO

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) arises from cholangiocytes in the intrahepatic bile duct and is the second most common type of liver cancer. Cholangiocytes express both oestrogen receptor-α and -ß, and oestrogens positively modulate cholangiocyte proliferation. Studies in women and men have reported higher circulating oestradiol is associated with increased ICC risk, further supporting a hormonal aetiology. However, no observational studies have examined the associations between exogenous hormone use and reproductive factors, as proxies of endogenous hormone levels, and risk of ICC. METHODS: We harmonised data from 1,107,498 women who enroled in 12 North American-based cohort studies (in the Liver Cancer Pooling Project, LCPP) and the UK Biobank between 1980-1998 and 2006-2010, respectively. Cox proportional hazards regression models were used to generate hazard ratios (HR) and 95% confidence internals (CI). Then, meta-analytic techniques were used to combine the estimates from the LCPP (n = 180 cases) and the UK Biobank (n = 57 cases). RESULTS: Hysterectomy was associated with a doubling of ICC risk (HR = 1.98, 95% CI: 1.27-3.09), compared to women aged 50-54 at natural menopause. Long-term oral contraceptive use (9+ years) was associated with a 62% increased ICC risk (HR = 1.62, 95% CI: 1.03-2.55). There was no association between ICC risk and other exogenous hormone use or reproductive factors. CONCLUSIONS: This study suggests that hysterectomy and long-term oral contraceptive use may be associated with an increased ICC risk.

15.
J Hepatol ; 73(4): 863-872, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32437829

RESUMO

BACKGROUND & AIMS: Gallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear. METHODS: We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study. RESULTS: During 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only. CONCLUSION: We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography. LAY SUMMARY: Our findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers.

16.
mSphere ; 5(1)2020 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-32250964

RESUMO

Few previous studies have assessed stability and "gold-standard" concordance of fecal sample collection methods for whole-genome shotgun metagenomic sequencing (WGSS), an increasingly popular method for studying the gut microbiome. We used WGSS data to investigate ambient temperature stability and putative gold-standard concordance of microbial profiles in fecal samples collected and stored using fecal occult blood test (FOBT) cards, fecal immunochemical test (FIT) tubes, 95% ethanol, or RNAlater. Among 15 Mayo Clinic employees, for each collection method, we calculated intraclass correlation coefficients (ICCs) to estimate stability of fecal microbial profiles after storage for 4 days at ambient temperature and concordance with immediately frozen, no-solution samples (i.e., the putative gold standard). ICCs were estimated for multiple metrics, including relative abundances of select phyla, species, KEGG k-genes (representing any coding sequence that had >70% identity and >70% query coverage with respect to a known KEGG ortholog), KEGG modules, and KEGG pathways; species and k-gene alpha diversity; and Bray-Curtis and Jaccard species beta diversity. ICCs for microbial profile stability were excellent (≥90%) for fecal samples collected via most of the collection methods, except those preserved in 95% ethanol. Concordance with the immediately frozen, no-solution samples varied for all collection methods, but the number of observed species and the beta diversity metrics tended to have higher concordance than other metrics. Our findings, taken together with previous studies and feasibility considerations, indicated that FOBT cards, FIT tubes, and RNAlater are acceptable choices for fecal sample collection methods in future WGSS studies.IMPORTANCE A major direction for future microbiome research is implementation of fecal sample collections in large-scale, prospective epidemiologic studies. Studying microbiome-disease associations likely requires microbial data to be pooled from multiple studies. Our findings suggest collection methods that are most optimal to be used standardly across future WGSS microbiome studies.

18.
mBio ; 11(1)2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32071266

RESUMO

Colorectal adenomas are precancerous lesions of colorectal cancer (CRC) that offer a means of viewing the events key to early CRC development. A number of studies have investigated the changes and roles of gut microbiota in adenoma and carcinoma development, highlighting its impact on carcinogenesis. However, there has been less of a focus on the gut metabolome, which mediates interactions between the host and gut microbes. Here, we investigated metabolomic profiles of stool samples from patients with advanced adenoma (n = 102), matched controls (n = 102), and patients with CRC (n = 36). We found that several classes of bioactive lipids, including polyunsaturated fatty acids, secondary bile acids, and sphingolipids, were elevated in the adenoma patients compared to the controls. Most such metabolites showed directionally consistent changes in the CRC patients, suggesting that those changes may represent early events of carcinogenesis. We also examined gut microbiome-metabolome associations using gut microbiota profiles in these patients. We found remarkably strong overall associations between the microbiome and metabolome data and catalogued a list of robustly correlated pairs of bacterial taxa and metabolomic features which included signatures of adenoma. Our findings highlight the importance of gut metabolites, and potentially their interplay with gut microbes, in the early events of CRC pathogenesis.IMPORTANCE Colorectal adenomas are precursors of CRC. Recently, the gut microbiota, i.e., the collection of microbes residing in our gut, has been recognized as a key player in CRC development. There have been a number of gut microbiota profiling studies for colorectal adenoma and CRC; however, fewer studies have considered the gut metabolome, which serves as the chemical interface between the host and gut microbiota. Here, we conducted a gut metabolome profiling study of colorectal adenoma and CRC and analyzed the metabolomic profiles together with paired microbiota composition profiles. We found several chemical signatures of colorectal adenoma that were associated with some gut microbes and potentially indicative of future CRC. This study highlights potential early-driver metabolites in CRC pathogenesis and guides further targeted experiments and thus provides an important stepping stone toward developing better CRC prevention strategies.


Assuntos
Adenoma/microbiologia , Neoplasias Colorretais/microbiologia , Fezes/microbiologia , Microbioma Gastrointestinal/fisiologia , Metaboloma , Metabolômica/métodos , Idoso , Bactérias/classificação , Bactérias/genética , Carcinogênese , Fezes/química , Feminino , Microbioma Gastrointestinal/genética , Humanos , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética
19.
Int J Cancer ; 146(8): 2156-2165, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31389007

RESUMO

Meat consumption has been postulated to increase the risk of breast cancer, but this association has not been consistently seen. We examined the association between consumption of different types of meat, meat mutagens and incident invasive breast cancer. Information on consumption of different meat categories and meat cooking practice behaviors was obtained from 42,012 Sister Study participants who completed a Block 1998 Food Frequency Questionnaire at enrollment (2003-2009) and satisfied eligibility criteria. Exposure to meat type and meat mutagens was calculated, and associations with invasive breast cancer risk were estimated using multivariable Cox proportional hazards regression. During follow-up (mean, 7.6 years), 1,536 invasive breast cancers were diagnosed at least 1 year after enrollment. Increasing consumption of red meat was associated with increased risk of invasive breast cancer (HRhighest vs. lowest quartile :1.23, 95% CI: 1.02-1.48, ptrend = 0.01). Conversely, increasing consumption of poultry was associated with decreased invasive breast cancer risk (HR highest vs. lowest quartile : 0.85; 95% CI: 0.72-1.00; ptrend = 0.03). In a substitution model with combined red meat and poultry consumption held constant, substituting poultry for red meat was associated with decreased invasive breast cancer risk (HR highest vs. lowest quartile of poultry consumption: 0.72, 95% CI: 0.58-0.89). No associations were observed for cooking practices, estimated heterocyclic amines or heme iron from red meat consumption with breast cancer risk. Red meat consumption may increase the risk of invasive breast cancer, whereas poultry consumption may be associated with reduced risk. Substituting poultry for red meat could reduce breast cancer risk.


Assuntos
Neoplasias da Mama/epidemiologia , Carne/estatística & dados numéricos , Animais , Culinária/métodos , Culinária/estatística & dados numéricos , Feminino , Humanos , Pessoa de Meia-Idade , Aves Domésticas , Modelos de Riscos Proporcionais , Porto Rico/epidemiologia , Carne Vermelha/estatística & dados numéricos
20.
Epidemiology ; 31(1): 136-144, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31577632

RESUMO

BACKGROUND: N-nitroso compounds are hypothesized human bladder carcinogens. We investigated ingestion of N-nitroso compound precursors nitrate and nitrite from drinking water and diet and bladder cancer in the New England Bladder Cancer Study. METHODS: Using historical nitrate measurements for public water supplies and measured and modeled values for private wells, as well as self-reported water intake, we estimated average nitrate concentrations (mg/L NO3-N) and average daily nitrate intake (mg/d) from 1970 to diagnosis/reference date (987 cases and 1,180 controls). We estimated overall and source-specific dietary nitrate and nitrite intakes using a food frequency questionnaire (1,037 cases and 1,225 controls). We used unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). We evaluated interactions with factors that may affect N-nitroso compound formation (i.e., red meat, vitamin C, smoking), and with water intake. RESULTS: Average drinking water nitrate concentration above the 95th percentile (>2.07 mg/L) compared with the lowest quartile (≤0.21 mg/L) was associated with bladder cancer (OR = 1.5, 95% CI = 0.97, 2.3; P trend = 0.01); the association was similar for average daily drinking water nitrate intake. We observed positive associations for dietary nitrate and nitrite intakes from processed meat (highest versus lowest quintile OR for nitrate = 1.4, 95% CI = 1.0, 2.0; P trend = 0.04; OR for nitrite = 1.5, 95% CI = 1.0, 2.1; P trend = 0.04, respectively), but not other dietary sources. We observed positive interactions between drinking water nitrate and red meat (P-interaction 0.05) and processed red meat (0.07). CONCLUSIONS: Our results suggest the importance of both drinking water and dietary nitrate sources as risk factors for bladder cancer.

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