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1.
Artigo em Inglês | MEDLINE | ID: mdl-33531435

RESUMO

BACKGROUND: Type 2 diabetes increases risk of developing colorectal cancer (CRC), but the association of pre-existing diabetes with CRC survival remains unclear. METHODS: We analyzed survival by diabetes status at cancer diagnosis among 4038 patients with CRC from two prospective U.S. cohorts. Cox proportional hazards regression was used to calculate HRs and 95% confidence intervals (CIs) for overall and cause-specific mortality, with adjustment for tumor characteristics and lifestyle factors. RESULTS: In the first 5 years after CRC diagnosis, diabetes was associated with a modest increase in overall mortality in women (HR, 1.22; 95% CI, 1.00-1.49), but not in men (HR, 0.83; 95% CI, 0.62-1.12; P heterogeneity by sex = 0.04). Beyond 5 years, diabetes was associated with substantially increased overall mortality with no evidence of sex heterogeneity; in women and men combined, the HRs were 1.45 (95% CI, 1.09-1.93) during >5 to 10 years and 2.58 (95% CI, 1.91-3.50) during >10 years. Compared with those without diabetes, CRC patients with diabetes had increased mortality from other malignancies (HR, 1.78; 95% CI, 1.18-2.67) and cardiovascular disease (HR, 1.93; 95% CI, 1.29-2.91). Only women with diabetes for more than 10 years had increased mortality from CRC (HR, 1.33; 95% CI, 1.01-1.76). CONCLUSIONS: Among patients with CRC, pre-existing diabetes was associated with increased risk of long-term mortality, particularly from other malignancies and cardiovascular disease. IMPACT: Our findings highlight the importance of cardioprotection and cancer prevention to CRC survivors with diabetes.

2.
BMC Med Res Methodol ; 21(1): 24, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33546607

RESUMO

BACKGROUND: Early pregnancy weights are needed to quantify gestational weight gain accurately. Different methods have been used in previous studies to impute early-pregnancy weights. However, no studies have systematically compared imputed weight accuracy across different imputation techniques. This study aimed to compare four methodological approaches to imputing early-pregnancy weight, using repeated measures of pregnancy weights collected from two pregnancy cohorts in Tanzania. METHODS: The mean gestational ages at enrollment were 17.8 weeks for Study I and 10.0 weeks for Study II. Given the gestational age distributions at enrollment, early-pregnancy weights were extrapolated for Study I and interpolated for Study II. The four imputation approaches included: (i) simple imputation based on the nearest measure, (ii) simple arithmetic imputation based on the nearest two measures, (iii) mixed-effects models, and (iv) marginal models with generalized estimating equations. For the mixed-effects model and the marginal model with generalized estimating equation methods, imputation accuracy was further compared across varying degrees of model flexibility by fitting splines and polynomial terms. Additional analyses included dropping third-trimester weights, adding covariate to the models, and log-transforming weight before imputation. Mean absolute error was used to quantify imputation accuracy. RESULTS: Study I included 1472 women with 6272 weight measures; Study II included 2131 individuals with 11,775 weight measures. Among the four imputation approaches, mixed-effects models had the highest accuracy (smallest mean absolute error: 1.99 kg and 1.60 kg for Studies I and II, respectively), while the other three approaches showed similar degrees of accuracy. Depending on the underlying data structure, allowing appropriate degree of model flexibility and dropping remote pregnancy weight measures may further improve the imputation performance. CONCLUSIONS: Mixed-effects models had superior performance in imputing early-pregnancy weight compared to other commonly used strategies.

3.
Ear Hear ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33577220

RESUMO

OBJECTIVES: Tinnitus and hearing loss commonly coexist, however, the temporal relation between tinnitus and hearing loss is complex and not fully understood. Our objective was to examine the longitudinal association between persistent tinnitus, bothersome tinnitus, and 3-year elevation of audiometric hearing thresholds. DESIGN: We conducted a longitudinal cohort study among 3106 women (mean age 59 years) who were participants in the Nurses' Health Study II (2012-2018). Information on tinnitus was obtained from biennial questionnaires. Longitudinal changes in air conduction thresholds (0.5 to 8 kHz) were assessed by pure-tone audiometry conducted by licensed audiologists at 19 audiology testing sites across the United States. Logistic regression was used to estimate multivariable-adjusted odds ratios (MVORs, 95% confidence interval [CI]) and evaluate the relations of persistent tinnitus (several days per week or more), bothersome tinnitus (interferes with work, sleep, or daily activities), and risk of 3-year elevation of hearing thresholds. RESULTS: Persistent tinnitus was associated with higher risk of 3-year elevation of hearing thresholds across a broad range of frequencies. Compared with women without tinnitus, the MVORs (95% CI) for ≥5-dB threshold elevation among women with persistent tinnitus were 1.01 (0.81, 1.25) at 0.5 kHz, 1.45 (1.17, 1.81) at 1 kHz, 1.25 (1.00, 1.56) at 2 kHz, 1.34 (1.07, 1.69) at 3 kHz, 1.34 (1.06, 1.70) at 4 kHz, 1.49 (1.16, 1.91) at 6 kHz, and 1.63 (1.25, 2.12) at 8 kHz. The magnitudes of the associations for ≥10-dB threshold elevation were similar. The magnitudes of the associations were substantially greater among women with bothersome tinnitus. For example, compared with women without tinnitus, the MVORs (95% CI) for a ≥5- and ≥10-dB elevation of hearing thresholds at 4 kHz were 2.97 (1.50, 5.89) and 2.79 (1.38, 5.65), respectively. The risk was elevated even among women with tinnitus who had clinically normal hearing thresholds at baseline. In analyses that examined the association of tinnitus and elevation of low-, mid- and high-frequency pure-tone average (PTA) hearing thresholds, the results were similar. Compared with women without tinnitus, the MVORs (95% CI) for ≥5-dB PTA elevation among women with persistent tinnitus were 1.29 (0.99,1.67) for LPTA(0.5,1,2 kHz); 1.44 (1.16, 1.78) for MPTA(3,4 kHz); and 1.38 (1.11, 1.71) for HPTA(6,8 kHz). For ≥10-dB elevation, the MVORs were 2.85 (1.55, 5.23), 1.52 (1.10, 2.09), and 1.41 (1.10, 1.82), respectively. CONCLUSION: Persistent tinnitus was associated with substantially higher risk of 3-year hearing threshold elevation, even among women with clinically normal baseline hearing. The magnitudes of the associations were greater among those with bothersome tinnitus. Monitoring hearing sensitivities may be indicated in patients with tinnitus, including those without audiometric evidence of hearing impairment.

4.
Matern Child Nutr ; : e13127, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33595899

RESUMO

Growth faltering in early childhood is prevalent in many low resource countries. Poor maternal dietary diversity during pregnancy has been linked with increased risk of fetal growth failure and adverse birth outcomes but may also influence subsequent infant growth. Our aim is to assess the role of prenatal maternal dietary diversity in infant growth in rural Uganda. Data from 3291 women and infant pairs enrolled in a birth cohort from 2014 to 2016 were analysed (NCT04233944). Maternal diets were assessed using dietary recall in the second or third trimesters of pregnancy. Maternal dietary diversity scores (DDS) were calculated using the FAO Minimum Dietary Diversity for Women (MDD-W). Cox regression models were used to evaluate associations of the DDS with the incidence of underweight, stunting and wasting in infants from 3 to 12 months, adjusting for confounding factors. The median DDS for women was low, at 3.0 (interquartile range 3.0-4.0), relative to the threshold of consuming five or more food groups daily. Infants of women in highest quartile of DDS (diverse diets) were less likely to be underweight (adjusted hazard ratio: 0.70, 95% confidence interval: 0.61, 0.80) compared with infants of women in Quartile 1 (p for trend <0.001) in models controlling for maternal factors. There was no significant association between DDS and stunting or wasting. Our findings suggest a relationship between higher maternal dietary diversity and lower risk of underweight in infancy. These findings suggest that programmes to improve infant growth could additionally consider strengthening prenatal dietary diversity to improve child outcomes globally.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33484419

RESUMO

PURPOSE: Evidence is mixed on whether cholesterol plays a role in the pathogenesis of glioma. We explored the associations between circulating lipids and glioma risk in three prospective cohorts. METHODS: Using prospective data from the UK Biobank, we examined the associations of total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), and triglycerides (TG) with glioma risk in multivariable (MV)-adjusted Cox proportional hazards models. Within the Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS), we carried out a matched, nested case-control study to examine these same associations. RESULTS: In the UK Biobank, 490 gliomas accrued over 2,358,964 person-years. TC was not significantly associated with glioma risk (MV HR = 1.20, 95% CI 0.89-1.61 for highest quartile vs. lowest, p-trend = 0.24). In 4-year lagged analyses (n = 229), higher TC was associated with significantly higher risk of glioma in men (MV HR = 2.26, 95% CI 1.32-3.89, p-trend = 0.002) but not women (MV HR = 1.28, 95% CI 0.61-2.68, p-trend = 0.72); similar findings emerged for HDL-C and, to a lesser extent, LDL-C. In the NHS/HPFS, no significant associations were found between cholesterol and glioma risk. No significant associations were identified for TG. CONCLUSION: In the UK Biobank, higher prediagnostic TC and HDL-C levels were associated with higher risk of glioma in 4-year lagged analyses, but not in non-lagged analyses, in men only. These findings merit further investigation, given that there are few risk factors and no reliable biomarkers of risk identified for glioma.

6.
Int J Epidemiol ; 2021 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-33484125

RESUMO

Molecular pathological epidemiology research provides information about pathogenic mechanisms. A common study goal is to evaluate whether the effects of risk factors on disease incidence vary between different disease subtypes. A popular approach to carrying out this type of research is to implement a multinomial regression in which each of the non-zero values corresponds to a bona fide disease subtype. Then, heterogeneity in the exposure effects across subtypes is examined by comparing the coefficients of the exposure between the different subtypes. In this paper, we explain why this common method potentially cannot recover causal effects, even when all confounders are measured, due to a particular type of selection bias. This bias can be explained by recognizing that the multinomial regression is equivalent to a series of logistic regressions; each compares cases of a certain subtype to the controls. We further explain how this bias arises using directed acyclic graphs and we demonstrate the potential magnitude of the bias by analysis of a hypothetical data set and by a simulation study.

7.
J Natl Cancer Inst ; 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-33225344

RESUMO

BACKGROUND: The influence of type 2 diabetes mellitus (T2D) duration on cancer incidence remains poorly understood. METHODS: We prospectively followed for cancer incidence 113 429 women in the Nurses' Health Study (1978-2014) and 45 604 men in the Health Professionals Follow-up Study (1988-2014) who were free of diabetes and cancer at baseline. Cancer incidences were ascertained by review of medical records. RESULTS: In the multivariable-adjusted model incident, T2D was associated with higher risk of cancers in the colorectum, lung, pancreas, esophagus, liver, thyroid, breast, and endometrium. The pooled hazard ratios (HRs) ranged from 1.21 (95% confidence interval [CI] = 1.06 to 1.38) for colorectal cancer to 3.39 (95% CI = 2.24 to 5.12) for liver cancer. For both composite cancer outcomes and individual cancers, the elevated risks did not further increase after 8 years of T2D duration. The hazard ratio for total cancer was 1.28 (95% CI = 1.17 to 1.40) for T2D duration of 4.1-6.0 years, 1.37 (95% CI = 1.25 to 1.50) for 6.1-8.0 years, 1.21 (95% CI = 1.09 to 1.35) for 8.1-10.0 years, and 1.04 (95% CI = 0.95 to 1.14) after 15.0 years. In a cross-sectional analysis, a higher level of plasma C-peptide was found among participants with prevalent T2D of up to 8 years than those without T2D, whereas a higher level of HbA1c was found for those with prevalent T2D of up to 15 years. CONCLUSIONS: Incident T2D was associated with higher cancer risk, which peaked at approximately 8 years after diabetes diagnosis. Similar duration-dependent pattern was observed for plasma C-peptide. Our findings support a role of hyperinsulinemia in cancer development.

8.
BMJ Glob Health ; 5(11)2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33177038

RESUMO

INTRODUCTION: Gestational weight gain (GWG) has important implications for maternal and child health and is an ideal modifiable factor for preconceptional and antenatal care. However, the average levels of GWG across all low-income and middle-income countries of the world have not been characterised using nationally representative data. METHODS: GWG estimates across time were computed using data from the Demographic and Health Surveys Program. A hierarchical model was developed to estimate the mean total GWG in the year 2015 for all countries to facilitate cross-country comparison. Year and country-level covariates were used as predictors, and variable selection was guided by the model fit. The final model included year (restricted cubic splines), geographical super-region (as defined by the Global Burden of Disease Study), mean adult female body mass index, gross domestic product per capita and total fertility rate. Uncertainty ranges (URs) were generated using non-parametric bootstrapping and a multiple imputation approach. Estimates were also computed for each super-region and region. RESULTS: Latin America and Caribbean (11.80 kg (95% UR: 6.18, 17.41)) and Central Europe, Eastern Europe and Central Asia (11.19 kg (95% UR: 6.16, 16.21)) were the super-regions with the highest GWG estimates in 2015. Sub-Saharan Africa (6.64 kg (95% UR: 3.39, 9.88)) and North Africa and Middle East (6.80 kg (95% UR: 3.17, 10.43)) were the super-regions with the lowest estimates in 2015. With the exception of Latin America and Caribbean, all super-regions were below the minimum GWG recommendation for normal-weight women, with Sub-Saharan Africa and North Africa and Middle East estimated to meet less than 60% of the minimum recommendation. CONCLUSION: The levels of GWG are inadequate in most low-income and middle-income countries and regions. Longitudinal monitoring systems and population-based interventions are crucial to combat inadequate GWG in low-income and middle-income countries.

9.
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.

10.
Cancer Epidemiol Biomarkers Prev ; 29(11): 2323-2331, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32917664

RESUMO

BACKGROUND: Higher total 25-hydroxyvitamin D [25(OH)D] levels are associated with improved survival among patients with colorectal cancer, but the relationships between circulating vitamin D binding protein (VDBP), and bioavailable or free 25(OH)D, and colorectal cancer survival remain unknown. METHODS: We examined the associations between prediagnostic plasma levels of vitamin D-related markers and survival among 603 White participants diagnosed with colorectal cancer from two prospective U.S. cohorts. Plasma VDBP and total 25(OH)D were directly measured, while bioavailable and free 25(OH)D was calculated using a validated formula on the basis of total 25(OH)D, VDBP, and albumin levels. Cox proportional hazards regression was used to estimate HRs for overall and colorectal cancer-specific mortality, with adjustment for other prognostic markers and potential confounders. RESULTS: Higher VDBP levels were associated with improved overall (P trend = 0.001) and colorectal cancer-specific survival (P trend = 0.02). Compared with patients in the lowest quartile, those in the highest quartile of VDBP had a multivariate HR of 0.58 [95% confidence interval (CI), 0.41-0.80] for overall mortality and 0.58 (95% CI, 0.37-0.91) for colorectal cancer-specific mortality. The results remained similar after further adjustment for total 25(OH)D levels. In contrast, neither bioavailable nor free 25(OH)D levels were associated with overall or colorectal cancer-specific mortality (all P trend > 0.15). CONCLUSIONS: Prediagnostic circulating concentrations of VDBP were positively associated with survival among patients with colorectal cancer. IMPACT: The clinical utility of VDBP as a prognostic marker warrants further exploration, as well as research into underlying mechanisms of action.

11.
Int J Biostat ; 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32892174

RESUMO

Progression-free survival (PFS), defined as the time from randomization to progression of disease or death, has been indicated as an endpoint to support accelerated approval of certain cancer drugs by the U.S. FDA. The standard Kaplan-Meier (KM) estimator of PFS, however, can result in significantly biased estimates. A major source for the bias results from the substitution of censored progression times with death times. Currently, to ameliorate this bias, several sensitivity analyses based on rather arbitrary definitions of PFS censoring are usually conducted. In addition, especially in the advanced cancer setting, patients with censored progression and observed death times have the potential to experience disease progression between those two times, in which case their true PFS time is actually between those times. In this paper, we present two alternative nonparametric estimators of PFS, which statistically incorporate survival data often available for those patients who are censored with respect to progression to obtain less biased estimates. Through extensive simulations, we show that these estimators greatly reduce the bias of the standard KM estimator and can also be utilized as alternative sensitivity analyses with a solid statistical basis in lieu of the arbitrarily defined analyses currently used. An example is also given using an ECOG-ACRIN Cancer Research Group advanced breast cancer study.

12.
Am J Clin Nutr ; 112(6): 1448-1455, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-32936862

RESUMO

BACKGROUND: Trimethylamine-N-oxide (TMAO) is a compound that is present in seafood and produced through human gut microbial metabolism of its precursors. Previous studies have suggested that elevated TMAO concentrations are associated with an increased risk of cardiovascular events. However, the association between diet and TMAO concentrations in free-living adult populations has not been adequately described. OBJECTIVES: The objective of this study was to identify dietary predictors of plasma TMAO concentrations. METHODS: TMAO concentrations were assessed in 2 fasting plasma samples collected 6 mo apart among 620 healthy men. Short-term and long-term dietary intakes were assessed during the same time-frame of blood collections via repeated 7-d dietary records (7DDRs) and a semiquantitative food-frequency questionnaire (SFFQ), respectively. We grouped individual food items into 21 groups and regressed against averaged TMAO concentrations. We also assessed the association between dietary scores and TMAO concentrations. RESULTS: In models adjusted for demographic characteristics and mutually adjusted for food groups, SFFQ-assessments of fish and egg intakes were significantly associated with increased TMAO concentration (ß = 0.082; 95% CI: 0.021, 0.14; P = 0.009 for fish; ß = 0.065; 95% CI: 0.004, 0.13; P = 0.039 for egg). The positive association between fish consumption and TMAO concentration was replicated in the 7DDR-assessments (ß = 0.12; 95% CI: 0.060, 0.18; P < 0.001). There was no association between red meat intake and TMAO concentrations. The unhealthful plant-based diet index (uPDI) was inversely associated (ß = -0.013; 95% CI: -0.021, -0.005; P = 0.001) and healthy dietary scores were positively correlated with TMAO concentration. CONCLUSIONS: TMAO concentration was significantly associated with fish intake, but not with red meat consumption. uPDI, an unhealthy dietary pattern, was inversely related to TMAO concentration. As such, this study suggests that in free-living populations, higher circulating concentrations of TMAO cannot simply be interpreted as a marker of unhealthy food intake or an unhealthy dietary pattern.

13.
Cancer Causes Control ; 31(10): 891-904, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32743740

RESUMO

PURPOSE: Although a growing body of evidence supports an early-life contribution to prostate cancer (PCa) development, few studies have investigated early-life diet, and only three have examined early-life dairy product intake, a promising candidate risk factor because of its known/suspected influence on insulin-like growth factor levels and height. METHODS: We used recalled dietary data from 162,816 participants in the NIH-AARP Diet and Health Study to investigate associations for milk, cheese, ice cream, total dairy, and calcium intake at ages 12-13 years with incident total (n = 17,729), advanced (n = 2,348), and fatal PCa (n = 827) over 14 years of follow-up. We calculated relative risks (RRs) and 95% confidence intervals (CIs) by Cox proportional hazards regression. RESULTS: We observed suggestive positive trends for milk, dairy, and calcium intake with total and/or advanced PCa (p-trends = 0.016-0.148). These trends attenuated after adjustment for additional components of adolescent diet, particularly red meat and vegetables/potatoes. In contrast, suggestive inverse trends were observed for cheese and ice cream intake with total and/or advanced PCa (p-trends = 0.043-0.153), and for milk, dairy, and calcium intake with fatal PCa (p-trend = 0.045-0.117). CONCLUSION: Although these findings provide some support for a role of adolescent diet in increasing PCa risk, particularly for correlates of milk intake or overall dietary patterns, our protective findings for cheese and ice cream intake with PCa risk and mortality, and for all dairy products with PCa mortality, suggest alternative explanations, such as the influence of early-life socioeconomic status, and increased PCa screening, earlier detection, and better PCa care.


Assuntos
Cálcio na Dieta , Laticínios , Neoplasias da Próstata/epidemiologia , Adolescente , Idoso , Animais , Criança , Dieta , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
14.
Cancer Prev Res (Phila) ; 13(10): 877-888, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32718943

RESUMO

Low-dose aspirin is recommended by the U.S. Preventive Services Task Force for primary prevention of colorectal cancer in certain individuals. However, broader implementation will require improved precision prevention approaches to identify those most likely to benefit. The major urinary metabolite of PGE2, 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), is a biomarker for colorectal cancer risk, but it is unknown whether PGE-M is modifiable by aspirin in individuals at risk for colorectal cancer. Adults (N = 180) who recently underwent adenoma resection and did not regularly use aspirin or NSAIDs were recruited to a double-blind, placebo-controlled, randomized trial of aspirin at 81 or 325 mg/day for 8-12 weeks. The primary outcome was postintervention change in urinary PGE-M as measured by LC/MS. A total of 169 participants provided paired urine samples for analysis. Baseline PGE-M excretion was 15.9 ± 14.6 (mean ± S.D, ng/mg creatinine). Aspirin significantly reduced PGE-M excretion (-4.7 ± 14.8) compared with no decrease (0.8 ± 11.8) in the placebo group (P = 0.015; mean duration of treatment = 68.9 days). Aspirin significantly reduced PGE-M levels in participants receiving either 81 (-15%; P = 0.018) or 325 mg/day (-28%; P < 0.0001) compared with placebo. In 40% and 50% of the individuals randomized to 81 or 325 mg/day aspirin, respectively, PGE-M reduction reached a threshold expected to prevent recurrence in 10% of individuals. These results support that aspirin significantly reduces elevated levels of PGE-M in those at increased colorectal cancer risk to levels consistent with lower risk for recurrent neoplasia and underscore the potential utility of PGE-M as a precision chemoprevention biomarker. The ASPIRED trial is registered as NCT02394769.

15.
BMJ ; 370: m2206, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641435

RESUMO

OBJECTIVE: To examine the associations between the intake of total and individual whole grain foods and the risk of type 2 diabetes. DESIGN: Prospective cohort studies. SETTING: Nurses' Health Study (1984-2014), Nurses' Health Study II (1991-2017), and Health Professionals Follow-Up Study (1986-2016), United States. PARTICIPANTS: 158 259 women and 36 525 men who did not have type 2 diabetes, cardiovascular disease, or cancer at baseline. MAIN OUTCOME MEASURES: Self-reports of incident type 2 diabetes by participants identified through follow-up questionnaires and confirmed by a validated supplementary questionnaire. RESULTS: During 4 618 796 person years of follow-up, 18 629 participants with type 2 diabetes were identified. Total whole grain consumption was categorized into five equal groups of servings a day for the three cohorts. After adjusting for lifestyle and dietary risk factors for diabetes, participants in the highest category for total whole grain consumption had a 29% (95% confidence interval 26% to 33%) lower rate of type 2 diabetes compared with those in the lowest category. For individual whole grain foods, pooled hazard ratios (95% confidence intervals) for type 2 diabetes in participants consuming one or more servings a day compared with those consuming less than one serving a month were 0.81 (0.77 to 0.86) for whole grain cold breakfast cereal, 0.79 (0.75 to 0.83) for dark bread, and 1.08 (1.00 to 1.17) for popcorn. For other individual whole grains with lower average intake levels, comparing consumption of two or more servings a week with less than one serving a month, the pooled hazard ratios (95% confidence intervals) were 0.79 (0.75 to 0.83) for oatmeal, 0.88 (0.82 to 0.94) for brown rice, 0.85 (0.80 to 0.90) for added bran, and 0.88 (0.78 to 0.98) for wheat germ. Spline regression showed a non-linear dose-response association between total whole grain intake and the risk of type 2 diabetes where the rate reduction slightly plateaued at more than two servings a day (P<0.001 for curvature). For whole grain cold breakfast cereal and dark bread, the rate reduction plateaued at about 0.5 servings a day. For consumption of popcorn, a J shaped association was found where the rate of type 2 diabetes was not significantly raised until consumption exceeded about one serving a day. The association between higher total whole grain intake and lower risk of type 2 diabetes was stronger in individuals who were lean than in those who were overweight or obese (P=0.003 for interaction), and the associations did not vary significantly across levels of physical activity, family history of diabetes, or smoking status. CONCLUSION: Higher consumption of total whole grains and several commonly eaten whole grain foods, including whole grain breakfast cereal, oatmeal, dark bread, brown rice, added bran, and wheat germ, was significantly associated with a lower risk of type 2 diabetes. These findings provide further support for the current recommendations of increasing whole grain consumption as part of a healthy diet for the prevention of type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Dieta Saudável , Grãos Integrais , Adulto , Diabetes Mellitus Tipo 2/prevenção & controle , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Estados Unidos/epidemiologia
16.
Am J Clin Nutr ; 112(3): 695-706, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32651998

RESUMO

BACKGROUND: Preterm birth (PTB), small for gestational age (SGA), and low birth weight (LBW) are risk factors for morbidity and mortality among infants. High-quality maternal diets during pregnancy may protect against these adverse birth outcomes. OBJECTIVES: The aim of this study was to prospectively examine the association of maternal dietary diversity and quality during pregnancy with birth outcomes among women in Dar es Salaam, Tanzania. METHODS: We analyzed data from 7553 HIV-negative pregnant women enrolled in a multivitamin trial at 12-27 weeks of gestation. Dietary intake was assessed using 24-h dietary recalls. Dietary diversity scores (DDS; range: 0-10) were computed as the number of food groups consumed by women, using FAO's Minimum Dietary Diversity for Women index. The Prime Diet Quality Score (PDQS; range: 0-42) assessed maternal diet quality based on consumption of 21 healthy and unhealthy food groups. Log binomial regression methods were used to assess associations of DDS and PDQS with PTB, SGA, LBW, and fetal loss. RESULTS: In the previous 24 h, 99.9% of all women had consumed cereal and staples, 57.9% meats, 4.7% eggs, and 0.5% nuts and seeds. Median DDS was 3.0 (IQR: 2.5-3.5). For the PDQS, all women consumed ≥4 servings/wk of green leafy vegetables and refined grains. Higher DDS was associated with lower risk of SGA (RR highest compared with lowest quintile: 0.74; 95% CI: 0.62, 0.89). Higher PDQS was associated with lower risk of PTB (RR highest compared with lowest quintile: 0.55; 95% CI: 0.46, 0.66), LBW (RR: 0.53; 95% CI: 0.40, 0.70), and fetal loss (RR: 0.53; 95% CI, 0.34, 0.82). CONCLUSIONS: PDQS was inversely associated with PTB, LBW, and fetal loss, and DDS was inversely associated with SGA. These findings suggest that in addition to dietary diversity, diet quality should be considered as important in understanding dietary risk factors for poor birth outcomes.This trial was registered at clinicaltrials.gov as NCT00197548.


Assuntos
Dieta/normas , Resultado da Gravidez , Fenômenos Fisiológicos da Nutrição Pré-Natal , Vitaminas/administração & dosagem , Adulto , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Gravidez , Nascimento Prematuro , Cuidado Pré-Natal , Tanzânia
17.
Lancet HIV ; 7(7): e463-e471, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32621874

RESUMO

BACKGROUND: Observational data suggest that low vitamin D status is associated with an increased incidence of pulmonary tuberculosis and mortality among people living with HIV. The primary aims of this study were to assess the effect of vitamin D3 supplementation on the risk of mortality and incidence of pulmonary tuberculosis among adults initiating antiretroviral therapy (ART). METHODS: This was a randomised, double-blind, placebo-controlled trial of vitamin D3 supplementation among adults living with HIV who initiated ART and had serum 25-hydroxyvitamin D concentrations of less than 30 ng/mL at four large HIV care and treatment centres in Dar es Salaam, Tanzania. Patients were excluded if they were younger than 18 years, pregnant at the time of randomisation, or were enrolled in any other clinical trial. Patients were randomly assigned 1:1 to receive either weekly oral 50 000 IU vitamin D3 supplements (cholecalciferol) for the first month of ART followed by daily 2000 IU vitamin D3 supplements or a matching weekly and daily placebo regimen. The randomisation list was computer-generated by a non-study statistician with sequence blocks of ten that were stratified by study clinic. Complete allocation concealment was ensured and patients, field team, and investigators were masked to group assignment. The trial follow-up duration was 1 year and the primary efficacy outcomes were death and incident pulmonary tuberculosis. An intention-to-treat analysis was followed for all-cause mortality; participants diagnosed with or receiving treatment for pulmonary tuberculosis at randomisation, or suspected to have tuberculosis at randomisation and who later had that diagnosis confirmed, were excluded from analyses of pulmonary tuberculosis incidence. Safety was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT01798680, and is completed. FINDINGS: Between Feb 24, 2014, and Feb 24, 2017, 6250 adults initiating ART had serum 25-hydroxyvitamin D screening, 4000 of whom were enrolled in the trial and followed up for 1 year (follow-up of all participants was completed on March 7, 2018). 2001 patients were randomly assigned to the vitamin D3 supplementation group, and 1999 to the placebo group. 415 deaths were recorded: 211 in the vitamin D3 group and 204 in the placebo group. Among all randomly assigned participants, there was no overall effect of vitamin D3 supplementation on the risk of mortality (hazard ratio [HR] 1·04, 95% CI 0·85-1·25; p=0·73). There was also no difference in the overall incidence of pulmonary tuberculosis between the vitamin D3 (50 events in 1812 patients analysed) and placebo groups (64 events in 1827 patients; HR 0·78, 0·54-1·13; p=0·19). The vitamin D3 regimen did not increase the risk of hypercalcaemia (three events in the vitamin D3 group and two events in the placebo group; relative risk 1·25, 95% CI 0·43-3·66; Fisher's exact p=1·00). 101 hospital admissions were reported in the vitamin D3 group and 94 in the placebo group (incidence rate ratio 1·06, 95% CI 0·80-1·41; p=0·66). INTERPRETATION: Additional research is needed before vitamin D3 supplementation should be considered for implementation in HIV care and treatment programmes for the prevention of pulmonary tuberculosis or mortality. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases.


Assuntos
Colecalciferol/farmacologia , Suplementos Nutricionais/análise , Infecções por HIV/tratamento farmacológico , Tuberculose Pulmonar/prevenção & controle , Adulto , Método Duplo-Cego , Feminino , Infecções por HIV/mortalidade , Humanos , Incidência , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Placebos , Tanzânia , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue
18.
Breast Cancer Res ; 22(1): 78, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32698885

RESUMO

BACKGROUND: Previous studies of fatty acids and breast cancer risk have shown mixed results, which may be due in part to tumor heterogeneity. Prior research has also illustrated an important role of specific fatty acids in immune regulation, T cell function, and inflammation, indicating that the effects of specific fatty acids on breast cancer risk may vary by tumor expression of immuno-inflammatory markers. We therefore aimed to evaluate the relationships between prediagnostic erythrocyte membrane fatty acids and breast cancer risk by tumor tissue expression of immuno-inflammatory markers (CD4, CD8, CD20, CD163, COX-2) and fatty acid synthase (FAS). METHODS: We conducted a matched case-control study nested within the Nurses' Health Study II (n = 235 cases and 235 controls). Blood samples were collected from 1996 to 1999. Tumor tissue blocks were collected for cases diagnosed after blood collection and through 2006. Unconditional nominal polytomous logistic regression adjusted for matching factors and potential confounders was used to assess whether associations between fatty acids and breast cancer risk varied by tumor expression subtype, ascertained via immunohistochemistry. Odds ratios (OR) and 95% confidence intervals (CI) were estimated separately by tumor expression subtype using unconditional logistic regression. RESULTS: Associations between fatty acids and breast cancer risk did not vary substantially by tumor CD4, CD20, CD163, or COX-2. However, n-3 polyunsaturated fatty acids (PUFAs) were inversely associated with CD8low but not CD8high cancers (CD8low ORT3 vs T1 = 0.45, 95% CI 0.23-0.87, Ptrend = 0.02; CD8high ORT3 vs T1 = 1.19, 95% CI 0.62-2.26, Ptrend = 0.62; Phet = 0.04). n-6 PUFAs were suggestively inversely associated with CD8high but not CD8low cancers (CD8high ORT3 vs T1 = 0.61, 95% CI 0.32-1.14, Ptrend = 0.11; CD8low ORT3 vs T1 = 1.63, 95% CI 0.87-3.04, Ptrend = 0.12; Phet = 0.02). Trans fatty acids were positively associated with FAShigh but not FASlow tumors (FAShigh ORT3 vs T1 = 2.94, 95% CI 1.46-5.91, Ptrend = 0.002; FASlow ORT3 vs T1 = 0.99, 95% CI 0.52-1.92, Ptrend = 0.97; Phet = 0.01). CONCLUSION: Results indicate that the effects of n-3 PUFAs, n-6 PUFAs, and trans fatty acids on breast cancer risk may vary by tumor tissue expression subtypes. Findings suggest potential immuno-modulatory and FAS-mediated mechanisms.


Assuntos
Neoplasias da Mama/metabolismo , Membrana Eritrocítica/metabolismo , Ácido Graxo Sintases/metabolismo , Ácidos Graxos/metabolismo , Mediadores da Inflamação/metabolismo , Adulto , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo
19.
Am J Med ; 133(10): 1180-1186, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32387319

RESUMO

BACKGROUND: Previous studies demonstrated higher risk of hearing loss among cigarette smokers, but longitudinal data on whether the risk is influenced by smoking cessation are limited. We prospectively investigated relations between smoking, smoking cessation, and risk of self-reported moderate or worse hearing loss among 81,505 women in the Nurses' Health Study II (1991-2013). METHODS: Information on smoking and hearing status was obtained from validated biennial questionnaires. Cox proportional hazards regression was used to estimate multivariable-adjusted relative risks (MVRR, 95% confidence interval). RESULTS: During 1,533,214 person-years of follow-up, 2760 cases of hearing loss were reported. Smoking was associated with higher risk of hearing loss and the risk tended to be higher with greater number of pack-years smoked. Compared with never smokers, the MVRR (95% confidence interval) among past smokers with 20+ pack-years of smoking was 1.30 (1.09-1.55) and 1.21 (1.02-1.43) for current smokers. The magnitude of elevated risk diminished with greater time since smoking cessation. Compared with never smokers, the MVRR among smokers who quit <5 years prior was 1.43 (1.17-1.75); 5-9 years prior was 1.27 (1.03-1.56); 10-14 years prior was 1.17 (0.96-1.41); and plateaued thereafter. Additional adjustment for pack-years smoking attenuated the results. CONCLUSIONS: The higher risk of hearing loss associated with smoking may diminish over time after quitting.


Assuntos
Fumar Cigarros/epidemiologia , Perda Auditiva/epidemiologia , Abandono do Hábito de Fumar/estatística & dados numéricos , Adulto , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia
20.
Gastroenterology ; 159(1): 241-256.e13, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32247020

RESUMO

BACKGROUND & AIMS: The molecular features of colorectal tumors differ with their anatomic location. Colorectal tumors are usually classified as proximal or distal. We collected data from 3 cohorts to identify demographic, clinical, anthropometric, lifestyle, and dietary risk factors for colorectal cancer (CRC) at 7 anatomic subsites. We examined whether the associations differ among refined subsites and whether there are trends in associations from cecum to rectum. METHODS: We collected data from the Nurses' Health Study, Nurses' Health Study 2, and Health Professionals Follow-up Study (45,351 men and 178,016 women, followed for a median 23 years) on 24 risk factors in relation to risk of cancer in cecum, ascending colon, transverse colon, descending colon, sigmoid colon, rectosigmoid junction, and rectum. Hazard ratios were estimated using Cox proportional hazards regression. We tested for linear and nonlinear trends in associations with CRC among subsites and within proximal colon, distal colon, and rectum. RESULTS: We documented 3058 cases of CRC (474 in cecum, 633 in ascending colon, 250 in transverse colon, 221 in descending colon, 750 in sigmoid colon, 202 in rectosigmoid junction, and 528 in rectum). The positive associations with cancer risk decreased, from cecum to rectum, for age and family history of CRC. In contrast, the inverse associations with cancer risk increased, from cecum to rectum, for endoscopic screening and intake of whole grains, cereal fiber, and processed red meat. There was a significant nonlinear trend in the association between CRC and female sex, with hazard ratios ranging from 1.73 for ascending colon cancer to 0.54 for sigmoid colon cancer. For proximal colon cancers, the association with alcohol consumption and smoking before age 30 years increased from the cecum to transverse colon. For distal colon cancers, the positive association with waist circumference in men was greater for descending vs sigmoid colon cancer. CONCLUSIONS: In an analysis of 3058 cases of CRC, we found that risk factor profiles differed for cancers along the colorectum. Proximal vs distal classifications are not sufficient to encompass the regional variations in colorectal tumor features and risk factors.

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