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1.
Ocul Surf ; 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33845221

RESUMO

PURPOSE: To investigate whether and how unhealthy sleep habits (i.e., the frequency of difficulty falling or staying asleep, and the frequency of waking up tired) and the duration of sleep are related to the prevalence of dry eye disease (DED) in a general population. METHODS: This study included a total of 106,282 subjects aged 40-74 years who participated in a baseline survey of the Japan Public Health Center-based Prospective Study for the Next Generation. DED was defined as the presence of clinically diagnosed DED or severe symptoms. Multivariable-adjusted logistic regression models were used to assess the relationships of various components of sleep status with DED. RESULTS: Higher frequencies of having difficulty falling or staying asleep, and waking up tired were significantly related to increased DED in both sexes (Ptrend<0.001). Compared with those with 8 h/day of sleep, shorter sleepers had an increased prevalence of DED in both sexes, although DED was increased among men who slept ≥10 h/day. By comparing participants with the greatest vs. the least difficulty of falling asleep, the multivariable-adjusted odds ratios (95% confidence interval [CI]) were 2.23 (95% CI, 1.99-2.49) for men and 1.91 (95% CI, 1.76-2.07) for women. When analyzed separately, the magnitude of each relationship was stronger with severe DED symptoms than with clinically diagnosed DED. CONCLUSIONS: Sleep deprivation and poor sleep quality were significantly related to DED in a Japanese population.

2.
Cancer Sci ; 112(4): 1579-1588, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33506574

RESUMO

Traditional observational studies have reported a positive association between higher body mass index (BMI) and the risk of colorectal cancer (CRC). However, evidence from other approaches to pursue the causal relationship between BMI and CRC is sparse. A two-sample Mendelian randomization (MR) study was undertaken using 68 single nucleotide polymorphisms (SNPs) from the Japanese genome-wide association study (GWAS) and 654 SNPs from the GWAS catalogue for BMI as sets of instrumental variables. For the analysis of SNP-BMI associations, we undertook a meta-analysis with 36 303 participants in the Japanese Consortium of Genetic Epidemiology studies (J-CGE), comprising normal populations. For the analysis of SNP-CRC associations, we utilized 7636 CRC cases and 37 141 controls from five studies in Japan, and undertook a meta-analysis. Mendelian randomization analysis of inverse-variance weighted method indicated that a one-unit (kg/m2 ) increase in genetically predicted BMI was associated with an odds ratio of 1.13 (95% confidence interval, 1.06-1.20; P value <.001) for CRC using the set of 68 SNPs, and an odds ratio of 1.07 (1.03-1.11, 0.001) for CRC using the set of 654 SNPs. Sensitivity analyses robustly showed increased odds ratios for CRC for every one-unit increase in genetically predicted BMI. Our MR analyses strongly support the evidence that higher BMI influences the risk of CRC. Although Asians are generally leaner than Europeans and North Americans, avoiding higher BMI seems to be important for the prevention of CRC in Asian populations.


Assuntos
Neoplasias Colorretais/etiologia , Neoplasias Colorretais/genética , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Japão , Masculino , Análise da Randomização Mendeliana/métodos , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
3.
Ophthalmol Retina ; 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32896678

RESUMO

PURPOSE: To determine the relationship of choroidal thickness with the early stages of age-related macular degeneration (AMD) and their disease features in a Japanese population. DESIGN: Cross-sectional survey PARTICIPANTS: A total of 1293 Japanese persons aged 65-86 years residing in the Saku area who underwent eye screening as part of the Japan Public Health Center-based Prospective Study. METHODS: Comprehensive ophthalmic assessment included fundus photography, measurement of intraocular pressure, and determination of refractive status. Optical coherence tomography with enhanced depth imaging mode was performed and subfoveal choroidal thickness was assessed. Multinomial logistic regression models were used to assess the relationships of choroidal thickness with the early stages of AMD, namely early AMD and intermediate AMD, and their disease features, after adjustment for potential confounders. MAIN OUTCOME MEASURES: Relationship of choroidal thickness with early AMD, intermediate AMD, and their disease features. RESULTS: Of the 1293 potential participants, 901 (mean age 73.2 years) had choroidal thickness data, fundus photographs of sufficient quality, and no concomitant retinal disease (including 5 late AMD cases). Mean choroidal thickness was 246.1 µm, and 15.1% had early AMD and 9.0% had intermediate AMD. After adjustment for age, sex, and refractive status, choroidal thickness was positively associated with the presence of intermediate AMD (for each 1-SD micrometer increase, OR: 1.43, 95% CI: 1.13-1.81), whereas no significant association was found with the presence of early AMD. Among intermediate AMD features, choroidal thickness was positively associated with the presence of AMD pigmentary abnormalities (associated with at least medium drusen; for each 1-SD micrometer increase, OR: 2.21, 95% CI: 1.42-3.42), whereas no significant association was found with the presence of large drusen alone. In addition, among large drusen subtypes, choroidal thickness was positively associated with the presence of pachydrusen (for each 1-SD micrometer increase, OR: 1.53, 95% CI: 1.10-2.13). Furthermore, exploratory analysis revealed that choroidal thickness was positively associated with the presence of non-AMD pigmentary abnormalities (for each 1-SD micrometer increase, OR: 1.92, 95% CI: 1.31-2.182). CONCLUSIONS: Choroidal thickness appears to be associated with the pathology of intermediate AMD and its features in Asians.

4.
Biomedicines ; 8(4)2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-32260530

RESUMO

Dry eye disease may develop and persist after cataract surgery; however, unilateral cases have not been fully documented. This cross-sectional, observational study was conducted in five eye clinics in Japan. A total of 1023 outpatients were initially enrolled, and 89 unilateral pseudophakic subjects with 1+ year of follow-up after uncomplicated cataract surgery were included. The tear break-up times (TBUTs) and keratoconjunctival staining results were compared between phakic and pseudophakic eyes. The mean age of the patients was 69.3 ± 10.4 years (32 men, 36.0%), and the mean postoperative period was 4.6 ± 4.4 (1-20) years. For the ophthalmic parameters, the TBUTs were 4.4 ± 1.9 and 3.8 ± 1.9 s (p < 0.001), the keratoconjunctival staining scores were 0.11 ± 0.38 and 0.22 ± 0.56 (p = 0.02), the spherical equivalents were -1.27 ± 2.51 and -0.99 ± 1.45 D (p = 0.21), the astigmatic errors were 0.79 ± 0.66 and 0.78 ± 0.58 D (p = 0.80), and the intraocular pressures were 13.6 ± 2.9 and 13.5 ± 2.6 mmHg (p = 0.62) for the phakic and pseudophakic eyes, respectively. The corneal status was significantly worse in the pseudophakic eyes than in the contralateral phakic eyes, even after more than one year after implant surgery. The present results suggested that long-term ocular surface problems should be examined further since they may not originate only from surgery or postoperative ocular surface diseases.

5.
Eye (Lond) ; 34(8): 1465-1475, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32123310

RESUMO

BACKGROUND/OBJECTIVES: To assess the long-term association between low-carbohydrate dietary patterns and incident primary open-angle glaucoma (POAG), and POAG subtypes defined by highest untreated intraocular pressure (IOP) and by pattern of visual field (VF) loss at diagnosis. SUBJECTS/METHODS: We followed 185,638 participants of three large US prospective cohorts biennially (1976-2016, 1986-2016 and 1991-2017). Deciles of three low-carbohydrate-diet scores were calculated to represent adherence to diets lower in carbohydrate and higher in protein and fat from any source, animal sources or plant sources. We confirmed POAG cases (n = 2112) by medical record review and used Cox proportional hazards models to estimate multivariable-adjusted relative risks (MVRRs) and 95% confidence intervals (CIs). RESULTS: There was no association between the three types of low-carbohydrate-diet scores and POAG: the MVRR for POAG in the highest vs. lowest deciles was 1.13 (95% CI, 0.91-1.39; Ptrend = 0.40) for the overall score; 1.10 (95% CI, 0.89-1.35; Ptrend = 0.38) for the animal score and 0.96 (95% CI, 0.79-1.18; Ptrend = 0.88) for the vegetable score. No differential associations by IOP level was found (Pheterogeneity ≥ 0.06). However, the vegetable score showed a suggestive inverse association with early paracentral VF loss (highest vs. lowest decile MVRR = 0.78 [95% CI, 0.55-1.10]; Ptrend = 0.12) but not with peripheral VF loss only (MVRR = 1.09 [95% CI, 0.83-1.44]; Ptrend = 0.14; Pheterogeneity = 0.03). CONCLUSIONS: Low-carbohydrate diets were not associated with risk of POAG. Our data suggested that higher consumption of fat and protein from vegetable sources substituting for carbohydrates was associated with lower risk of the POAG subtype with initial paracentral VF loss.

6.
Sci Rep ; 10(1): 5355, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32210291

RESUMO

Although a meta-analysis previously suggested a positive relationship between diabetes and intraocular pressure (IOP), the interrelationships among diabetes, IOP, and other ocular biometric parameters remain unclear. The present study investigated the relationships of diabetes, haemoglobin A1c (HbA1c), and serum glucose with IOP and ocular hypertension (IOP > 21 mmHg) in non-glaucomatous Japanese adults living in Chikusei City. Diabetes was defined as a self-reported history of diabetes, the use of antidiabetic medication, or HbA1c levels ≥6.5%. Among 6,786 enrolled participants aged 40 years and above, 734 were classified as diabetic (10.8%). After adjusting for several confounders, the IOP values were significantly higher in participants with diabetes than in those without diabetes (14.4 ± 0.1 vs. 13.9 ± 0.1 mmHg, P < 0.001) and were also significantly increased in those with elevated HbA1c and serum glucose levels (both P < 0.001). Moreover, diabetes was significantly related to ocular hypertension (multivariable-adjusted odds ratio, 1.75; 95% confidence interval, 1.09-2.81; P < 0.05). The positive influence of diabetes with ocular hypertension was consistent even after adjustment for central corneal thickness. In conclusion, diabetes, elevated HbA1c, and increased serum glucose are significant contributing factors for elevated IOP.

7.
Sci Rep ; 10(1): 779, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964909

RESUMO

The study subjects were residents of Chikusei city, Japan, aged 40 years or older who attended annual health check-up programs and participated in the JPHC-NEXT Eye Study which performed non-mydriatic fundus photography of both eyes. The relationship of glaucomatous fundus changes such as optic disc cupping (cup to disc ratio ≥ 0.7) and retinal nerve fiber layer defect (NFLD) with the presence of epiretinal membrane (ERM) were examined cross-sectionally. A total of 1990 persons gave consent to participate in this study in 2013. The overall prevalence of ERM was 12.9%. Of these, 1755 had fundus photographs of sufficient quality and no history of intraocular surgery (mean age: 62.3 ± 10.0 years). After adjusting for age, sex and refractive error, NFLD was positively associated with the presence of ERM (odds ratio [OR]: 2.48; 95% confidence interval [CI]: 1.24, 4.96; P = 0.010), but optic disc cupping was not (OR: 1.33; CI: 0.71, 2.48; P = 0.37). The results did not necessarily suggest an association between glaucoma and ERM, but indicated an association between NFLD and ERM.


Assuntos
Membrana Epirretiniana/epidemiologia , Glaucoma/epidemiologia , Fibras Nervosas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Membrana Epirretiniana/diagnóstico por imagem , Membrana Epirretiniana/patologia , Feminino , Glaucoma/diagnóstico por imagem , Glaucoma/patologia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Disco Óptico/diagnóstico por imagem , Prevalência
8.
Int J Cancer ; 146(9): 2383-2393, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31276608

RESUMO

Anthropometric measurements, such as body mass index (BMI), waist circumference, and body fat percentage, have been used as indicators of obesity. Despite evidence that excess body fat is a risk factor for colorectal carcinoma (CRC), the magnitude of the association of BMI and other obesity indicators with the long-term risk of CRC remains unclear. Utilizing a Cox proportional hazards regression model, we examined differential associations between predicted body fat percentage and BMI with the risk of CRC (n = 2,017). The associations between CRC incidence and different adiposity measurements were also assessed. Predicted body fat percentage had a similar increased risk of CRC risk as BMI. In multivariable-adjusted analyses, the hazard ratio for CRC in the second to fifth quintiles (compared to the first quintile) of predicted body fat percentage were 1.32, 1.31, 1.53 and 2.09 for men (ptrend < 0.001) and 0.91, 0.90, 0.98 and 1.15 for women (ptrend = 0.03). Among various anthropometric measurements, predicted fat mass and waist circumference were slightly more strongly associated with CRC risk than BMI. In conclusion, the novel anthropometric prediction equations provided further evidence that a greater amount of body fat might contribute to CRC risk in both sexes. An innovative approach enabled us to estimate the susceptibilities of specific body composition with CRC risk, in an inexpensive and minimally invasive manner. Furthermore, the typically used measures of BMI and waist circumference are robust measures of adiposity to predict cancer risk in a relatively healthy population.


Assuntos
Tecido Adiposo/fisiopatologia , Adiposidade , Índice de Massa Corporal , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Obesidade Abdominal/complicações , Idoso , Antropometria , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco
9.
Ocul Surf ; 18(1): 56-63, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31563549

RESUMO

PURPOSE: This population-based, cross-sectional study was performed to assess the influence of life-style modalities, including physical activity, sedentary behaviors, and visual display terminal (VDT) use, on the prevalence of dry eye disease (DED). METHODS: The study included a total of 102,582 participants aged 40-74 years, from the Japan Public Health Center-based Prospective Study for the Next Generation, a large nationwide prospective ongoing Japanese cohort study. Logistic regression analyses were used to investigate the relationship of total and leisure-time physical activity, duration of sedentary behaviors, and VDT use (hours/day) with DED. RESULTS: Among 47,346 men and 55,236 women, 25,234 (8315 males and 16,919 females) cases of DED were documented. Total physical activity was significantly related to decreased DED in both sexes; for the highest vs. lowest total physical activity quartiles, the multivariable-adjusted odds ratios (ORs) for DED were 0.90 (95% confidence interval [CI], 0.84-0.97; Ptrend<0.03) and 0.91 (95% CI, 0.86-0.95; Ptrend<0.001) for men and women, respectively. Conversely, prolonged sedentary behaviors and VDT use had significantly higher prevalence of DED in both sexes (Ptrend<0.001). Notably, the favorable effect of total physical activity on decreased DED in women was more prevalent with prolonged VDT use (≥2 h/day) (Pinteraction<0.01). In men, the duration of VDT use or sitting was a significant modifier of the inverse relationship between leisure-time physical activity and DED (Pinteraction<0.05). CONCLUSIONS: Physical inactivity, prolonged sedentary behaviors, and use of VDT were related to increased susceptibility to DED among middle-aged to older Japanese adults.

10.
J Clin Med ; 8(2)2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30736453

RESUMO

Despite the increased awareness of early prophylaxis and treatment for dry eye disease (DED) during the first few weeks after cataract surgery, the chronic effect of cataract surgery on the risk of ocular surface abnormalities has not been fully explored. This study was to assess the prevalence of DE subjective symptoms and clinical tests according to the cataract surgery. A total of 172 patients who underwent bilateral cataract surgeries at least 5 months before the recruitment date and 1225 controls with no cataracts were evaluated for their subjective DE symptoms (dry sensation, foreign-body sensation, ocular pain, ocular fatigue, sensitivity to bright light, and blurred vision) and ophthalmic parameters (tear break-up time, keratoconjunctival staining scores, and maximum blinking interval). The presence of subjective DE symptoms was generally inversely associated with cataract surgeries, whereas abnormal clinical tests were more pronounced among postsurgical cataract patients than among controls. Pseudophakic patients showed a 57% increased prevalence of severe keratoconjunctivitis, compared to controls (P = 0.02). In contrast, among subjective DE symptoms, significantly lower odds of sensitivity to bright light were detected among cases than controls; the multivariable-adjusted odds ratio (95% confidence interval) comparing pseudophakic patients with noncataract patients was 0.56 (0.34⁻0.92) (P = 0.02). In conclusion, persistent tear instability and corneal epitheliopathy were found even at several months or more after cataract surgery. This study demonstrates the importance of evaluating ocular surface conditions in pseudophakic patients, even if they lack DE symptoms.

11.
JNCI Cancer Spectr ; 2(4): pky058, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31276098

RESUMO

Background: Evidence suggests that high-level physical activity may potentially reduce cancer mortality through its immune enhancement effect. We therefore hypothesized that survival benefits associated with physical activity might be stronger in colorectal carcinomas with lower immune reaction at diagnosis. Methods: Using molecular pathological epidemiology databases of 470 colon and rectal carcinoma cases in the Nurses' Health Study and the Health Professionals Follow-up Study, we assessed the prognostic association of postdiagnosis physical activity in strata of densities of CD3+ cells, CD8+ cells, CD45RO (PTPRC)+ cells, or FOXP3+ cells in tumor tissue. Cox proportional hazards regression model was used to adjust for potential confounders, including microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element-1 methylation, KRAS, BRAF, and PIK3CA mutations, and expression of CTNNB1 (beta-catenin), PTGS2 (cyclooxygenase-2), and IRS1. Results: The association of postdiagnosis physical activity with colorectal cancer-specific mortality differed by CD3+ cell density (P interaction < .001). Multivariable-adjusted colorectal cancer-specific mortality hazard ratios for a quartile-unit increase in physical activity were 0.56 (95% confidence interval = 0.38 to 0.83) among cases with the lowest quartile of CD3+ cell density compared with 1.14 (95% confidence interval = 0.79 to 1.65) in cases with the highest quartile. We observed no differential survival association of physical activity by densities of CD8+ cells, CD45RO+ cells, or FOXP3+ cells. Conclusions: The association between postdiagnosis physical activity and colorectal cancer survival appeared stronger for carcinomas with lower T cell infiltrates, suggesting an interactive effect of exercise and immunity on colorectal cancer progression.

12.
Eur J Epidemiol ; 32(5): 393-407, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28510098

RESUMO

Previous studies suggest that abnormal energy balance status may dysregulate intestinal epithelial homeostasis and promote colorectal carcinogenesis, yet little is known about how host energy balance and obesity influence enterocyte differentiation during carcinogenesis. We hypothesized that the association between high body mass index (BMI) and colorectal carcinoma incidence might differ according to tumor histopathologic differentiation status. Using databases of the Nurses' Health Study and Health Professionals Follow-up Study, and duplication-method Cox proportional hazards models, we prospectively examined an association between BMI and the incidence of colorectal carcinoma subtypes classified by differentiation features. 120,813 participants were followed for 26 or 32 years and 1528 rectal and colon cancer cases with available tumor pathological data were documented. The association between BMI and colorectal cancer risk significantly differed depending on the presence or absence of poorly-differentiated foci (Pheterogeneity = 0.006). Higher BMI was associated with a higher risk of colorectal carcinoma without poorly-differentiated foci (≥30.0 vs. 18.5-22.4 kg/m2: multivariable-adjusted hazard ratio, 1.87; 95% confidence interval, 1.49-2.34; Ptrend < 0.001), but not with risk of carcinoma with poorly-differentiated foci (Ptrend = 0.56). This differential association appeared to be consistent in strata of tumor microsatellite instability or FASN expression status, although the statistical power was limited. The association between BMI and colorectal carcinoma risk did not significantly differ by overall tumor differentiation, mucinous differentiation, or signet ring cell component (Pheterogeneity > 0.03, with the adjusted α of 0.01). High BMI was associated with risk of colorectal cancer subtype containing no poorly-differentiated focus. Our findings suggest that carcinogenic influence of excess energy balance might be stronger for tumors that retain better intestinal differentiation throughout the tumor areas.


Assuntos
Índice de Massa Corporal , Diferenciação Celular/genética , Neoplasias Colorretais/patologia , Obesidade , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Epigenômica , Seguimentos , Humanos , Incidência , Instabilidade de Microssatélites , Epidemiologia Molecular , Obesidade/complicações , Patologia Molecular , Fatores de Risco , Estados Unidos/epidemiologia
13.
Int J Cancer ; 140(12): 2648-2656, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28268248

RESUMO

Accumulating evidence suggests that post-diagnostic insulin levels may influence colorectal cancer (CRC) survival. Yet, no previous study has examined CRC survival in relation to a post-diagnostic diet rich in foods that increase post-prandial insulin levels. We hypothesized that glycemic and insulin scores (index or load; derived from food frequency questionnaire data) may be associated with survival from specific CRC subtypes sensitive to the insulin signaling pathway. We prospectively followed 1,160 CRC patients from the Nurses' Health Study (1980-2012) and Health Professionals Follow-Up Study (1986-2012), resulting in 266 CRC deaths in 10,235 person-years. CRC subtypes were defined by seven tumor biomarkers (KRAS, BRAF, PIK3CA mutations, and IRS1, IRS2, FASN and CTNNB1 expression) implicated in the insulin signaling pathway. For overall CRC and each subtype, hazard ratio (HR) and 95% confidence interval (95% CI) for an increase of one standard deviation in each of glycemic and insulin scores were estimated using time-dependent Cox proportional hazards model. We found that insulin scores, but not glycemic scores, were positively associated with CRC mortality (HR = 1.19, 95% CI = 1.02-1.38 for index; HR = 1.23, 95% CI = 1.04-1.47 for load). The significant positive associations appeared more pronounced among PIK3CA wild-type cases and FASN-negative cases, with HR ranging from 1.36 to 1.60 across insulin scores. However, we did not observe statistically significant interactions of insulin scores with PIK3CA, FASN, or any other tumor marker (p interaction > 0.12). While additional studies are needed for definitive evidence, a high-insulinogenic diet after CRC diagnosis may contribute to worse CRC survival.


Assuntos
Biomarcadores Tumorais/metabolismo , Glicemia/metabolismo , Neoplasias Colorretais/metabolismo , Dieta , Insulina/metabolismo , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Pessoal de Saúde/estatística & dados numéricos , Humanos , Masculino , Análise Multivariada , Mutação , Enfermeiras e Enfermeiros/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de Sobrevida
14.
Clin Transl Gastroenterol ; 7(11): e200, 2016 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-27811909

RESUMO

OBJECTIVES: Evidence suggests a possible role of Fusobacterium nucleatum in colorectal carcinogenesis, especially in right-sided proximal colorectum. Considering a change in bowel contents and microbiome from proximal to distal colorectal segments, we hypothesized that the proportion of colorectal carcinoma enriched with F. nucleatum might gradually increase along the bowel subsites from rectum to cecum. METHODS: A retrospective, cross-sectional analysis was conducted on 1,102 colon and rectal carcinomas in molecular pathological epidemiology databases of the Nurses' Health Study and the Health Professionals Follow-up Study. We measured the amount of F. nucleatum DNA in colorectal tumor tissue using a quantitative PCR assay and equally dichotomized F. nucleatum-positive cases (high vs. low). We used multivariable logistic regression analysis to examine the relationship of a bowel subsite variable (rectum, rectosigmoid junction, sigmoid colon, descending colon, splenic flexure, transverse colon, hepatic flexure, ascending colon, and cecum) with the amount of F. nucleatum. RESULTS: The proportion of F. nucleatum-high colorectal cancers gradually increased from rectal cancers (2.5%; 4/157) to cecal cancers (11%; 19/178), with a statistically significant linear trend along all subsites (P<0.0001) and little evidence of non-linearity. The proportion of F. nucleatum-low cancers was higher in rectal, ascending colon, and cecal cancers than in cancers of middle segments. CONCLUSIONS: The proportion of F. nucleatum-high colorectal cancers gradually increases from rectum to cecum. Our data support the colorectal continuum model that reflects pathogenic influences of the gut microbiota on neoplastic and immune cells and challenges the prevailing two-colon (proximal vs. distal) dichotomy paradigm.

15.
Int J Cancer ; 139(4): 854-68, 2016 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-27037951

RESUMO

Higher body mass index (BMI), higher body adiposity and obesity have been associated with increased risk of colorectal cancer. Evidence suggests that excess energy balance may influence systemic immune and inflammatory status. Thus, we hypothesized that the positive association between BMI and colorectal cancer risk might differ according to colorectal carcinoma subtypes according to levels of histopathological lymphocytic reaction to tumor. We collected biennial questionnaire data on weight and baseline height information in two prospective cohort studies, the Nurses' Health Study (1980-2010) and the Health Professionals Follow-up Study (1986-2010). Utilizing duplication-method Cox proportional hazards regression models, we prospectively assessed the association between BMI and risk of colorectal cancer subtypes according to the degree of Crohn's-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, tumor-infiltrating lymphocytes, the overall lymphocytic reaction score, or T-cell [CD3(+) , CD8(+) , CD45RO (PTPRC)(+) or FOXP3(+) ] density in tumor tissue. Statistical significance level was adjusted for multiple hypotheses testing by Bonferroni correction. During follow up of 1,708,029 men and women (over 3,346,752 person-years), we documented 1,436 incident rectal and colon cancer cases with available formalin-fixed paraffin-embedded tumor tissue materials and pathological immunity data. BMI was significantly associated with higher risk of overall colorectal cancer (Ptrend < 0.001); however, the association of BMI with colorectal carcinoma risk did not significantly differ by the level of lymphocytic reaction or T-cell infiltration in tumor tissue status (Pheterogeneity > 0.10). BMI may be associated with risk of colorectal cancer regardless of levels of lymphocytic response to tumor.


Assuntos
Índice de Massa Corporal , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Linfócitos do Interstício Tumoral/imunologia , Idoso , Biomarcadores , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Comorbidade , Feminino , Humanos , Ativação Linfocitária/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Gradação de Tumores , Sistema de Registros , Risco , Microambiente Tumoral/imunologia
16.
Ann Surg Oncol ; 23(3): 908-17, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26577117

RESUMO

BACKGROUND: High-level physical activity is associated with lower colorectal cancer (CRC) mortality, likely through insulin sensitization. Insulin receptor substrate 1 (IRS1) is a mediator of insulin and insulin-like growth factor (IGF) signaling pathways, and its down-regulation is associated with insulin resistance. Therefore, we hypothesized that tumor IRS1 expression status might modify cellular sensitivity to insulin and IGF, and the prognostic association of physical activity. METHODS: We assessed IRS1 expression level in 371 stage I-III rectal and colon cancers in the Nurses' Health Study and the Health Professionals Follow-up Study by immunohistochemistry. In survival analysis, Cox proportional hazards model was used to assess an interaction between post-diagnosis physical activity (ordinal scale of sex-specific quartiles Q1 to Q4) and IRS1 expression (ordinal scale of negative, low, and high), controlling for potential confounders, including microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element-1 (LINE-1) methylation level, and KRAS, BRAF, and PIK3CA mutation status. RESULTS: There was a statistically significant interaction between post-diagnosis physical activity and tumor IRS1 expression in CRC-specific mortality analysis (P interaction = 0.005). Multivariable hazard ratio (95% confidence interval) for higher post-diagnosis physical activity (Q3-Q4 vs. Q1-Q2) was 0.15 (0.02-1.38) in the IRS1-negative group, 0.45 (0.19-1.03) in the IRS1-low group, and 1.32 (0.50-3.53) in the IRS1-high group. CONCLUSIONS: The association of post-diagnosis physical activity with colorectal carcinoma patient survival may differ by tumor IRS1 expression level. If validated, tumor IRS1 expression status may serve as a predictive marker to identify subgroups of patients who might gain greater survival benefit from an increased level of exercise.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/mortalidade , Terapia por Exercício/mortalidade , Proteínas Substratos do Receptor de Insulina/metabolismo , Idoso , Biomarcadores Tumorais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/terapia , Metilação de DNA , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Elementos Nucleotídeos Longos e Dispersos , Masculino , Instabilidade de Microssatélites , Mutação/genética , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Análise Serial de Tecidos
17.
Invest Ophthalmol Vis Sci ; 56(12): 7021-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26523386

RESUMO

PURPOSE: There is considerable evidence for systemic vascular dysfunction in primary open-angle glaucoma (POAG). We performed nailfold capillary video microscopy to observe directly the nature of nonocular microvasculature abnormalities in POAG. METHODS: We enrolled 199 POAG patients and 124 control subjects from four sites. We used JH-1004 capillaroscopes to perform nailfold capillary video microscopy on the fourth and fifth digits of each subject's nondominant hand. Videos were evaluated for hemorrhages, dilated capillary loops > 50 µm, and avascular zones > 100 µm by graders masked to case status. Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) for POAG were obtained by means of logistic regression analyses that were applied to data from all cases and controls. Corresponding estimates of moderate or severe POAG versus mild POAG (based on the Hodapp-Anderson-Parrish scale) were obtained among cases only. RESULTS: After controlling for demographic factors, family history of glaucoma, systemic diseases, and use of anticoagulation and antiplatelet therapy, for each 100 nailfold capillaries assessed, all types of microvascular abnormalities were significantly associated with POAG. Specifically, the presence of any dilated capillaries (OR = 2.9; 95% CI, 1.6-5.6), avascular zones (OR = 4.4; 95% CI, 1.7-11.3) and hemorrhages (OR = 12.2; 95% CI, 5.9-25.1) were associated with POAG. Among cases, the frequency of microvascular abnormalities was not associated with glaucoma severity (P ≥ 0.43). CONCLUSIONS: These data provided support for nonocular capillary bed abnormalities in POAG. Comparable vascular abnormalities in the optic nerve may render it susceptible to glaucomatous damage.


Assuntos
Glaucoma de Ângulo Aberto/diagnóstico , Pressão Intraocular , Unhas/irrigação sanguínea , Malformações Vasculares/complicações , Campos Visuais , Idoso , Estudos Transversais , Feminino , Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Masculino , Angioscopia Microscópica , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Malformações Vasculares/diagnóstico , Malformações Vasculares/fisiopatologia , Gravação em Vídeo , Testes de Campo Visual
19.
J Cyst Fibros ; 10(4): 243-52, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21441077

RESUMO

BACKGROUND: The G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) is a common cause of cystic fibrosis (CF). G551D-CFTR is characterized by an extremely low open probability despite its normal trafficking to the plasma membrane. Numerous small molecules have been shown to increase the activity of G551D-CFTR presumably by binding to the CFTR protein. METHODS: We investigated the effect of curcumin, genistein and their combined application on G551D-CFTR activity using the patch clamp technique. RESULTS: Curcumin increased G551D-CFTR whole-cell and single-channel currents less than genistein did at their maximally effective concentrations. However, curcumin further increased the channel activity of G551D-CFTR that had been already maximally potentiated by genistein, up to ~50% of the WT-CFTR level. In addition, the combined application of genistein and curcumin over a lower concentration range synergistically rescued the gating defect of G551D-CFTR. CONCLUSIONS: The additive effects between curcumin and genistein not only support the hypothesis that multiple mechanisms are involved in the action of CFTR potentiators, but also pose pharmaceutical implications in the development of drugs for CF pharmacotherapy.


Assuntos
Curcumina/farmacologia , Regulador de Condutância Transmembrana em Fibrose Cística/fisiologia , Fibrose Cística/tratamento farmacológico , Genisteína/farmacologia , Ativação do Canal Iônico/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Células CHO , Cricetinae , Cricetulus , Fibrose Cística/fisiopatologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Sinergismo Farmacológico , Proteínas de Fluorescência Verde/genética , Humanos , Mutação de Sentido Incorreto , Técnicas de Patch-Clamp , Fitoestrógenos/farmacologia , Transfecção
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