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Dietary Insulin Load and Cancer Recurrence and Survival in Patients With Stage III Colon Cancer: Findings From CALGB 89803 (Alliance).
Morales-Oyarvide, V, Yuan, C, Babic, A, Zhang, S, Niedzwiecki, D, Brand-Miller, JC, Sampson-Kent, L, Ye, X, Li, Y, Saltz, LB, et al
Journal of the National Cancer Institute. 2019;(2):170-179
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BACKGROUND Evidence suggests that diets inducing postprandial hyperinsulinemia may be associated with increased cancer-related mortality. The goal of this study was to assess the influence of postdiagnosis dietary insulin load and dietary insulin index on outcomes of stage III colon cancer patients. METHODS We conducted a prospective observational study of 1023 patients with resected stage III colon cancer enrolled in an adjuvant chemotherapy trial who reported dietary intake halfway through and six months after chemotherapy. We evaluated the association of dietary insulin load and dietary insulin index with cancer recurrence and survival using Cox proportional hazards regression adjusted for potential confounders; statistical tests were two-sided. RESULTS High dietary insulin load had a statistically significant association with worse disease-free survival (DFS), comparing the highest vs lowest quintile (adjusted hazard ratio [HR] = 2.77, 95% confidence interval [CI] = 1.90 to 4.02, Ptrend < .001). High dietary insulin index was also associated with worse DFS (highest vs lowest quintile, HR = 1.75, 95% CI = 1.22 to 2.51, Ptrend= .01). The association between higher dietary insulin load and worse DFS differed by body mass index and was strongest among patients with obesity (HR = 3.66, 95% CI = 1.88 to 7.12, Pinteraction = .04). The influence of dietary insulin load on cancer outcomes did not differ by mutation status of KRAS, BRAF, PIK3CA, TP53, or microsatellite instability. CONCLUSIONS Patients with resected stage III colon cancer who consumed a high-insulinogenic diet were at increased risk of recurrence and mortality. These findings support the importance of dietary management following resection of colon cancer, and future research into underlying mechanisms of action is warranted.
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Coffee consumption and plasma biomarkers of metabolic and inflammatory pathways in US health professionals.
Hang, D, Kværner, AS, Ma, W, Hu, Y, Tabung, FK, Nan, H, Hu, Z, Shen, H, Mucci, LA, Chan, AT, et al
The American journal of clinical nutrition. 2019;(3):635-647
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BACKGROUND Coffee consumption has been linked to lower risk of various health outcomes. However, the biological pathways mediating the associations remain poorly understood. OBJECTIVES The aim of this study was to assess the association between coffee consumption and concentrations of plasma biomarkers in key metabolic and inflammatory pathways underlying common chronic diseases. METHODS We investigated the associations of total, caffeinated, and decaffeinated coffee consumption with 14 plasma biomarkers, including C-peptide, insulin-like growth factor 1 (IGF-1), IGF binding protein (IGFBP) 1, IGFBP-3, estrone, total and free estradiol, total and free testosterone, sex hormone-binding globulin (SHBG), total adiponectin, high-molecular-weight (HMW) adiponectin, leptin, C-reactive protein (CRP), interleukin 6 (IL-6), and soluble tumor necrosis factor receptor 2 (sTNFR-2). Data were derived from 2 cohorts of 15,551 women (Nurses' Health Study) and 7397 men (Health Professionals Follow-Up Study), who provided detailed dietary data before blood draw and were free of diabetes, cardiovascular disease, or cancer at the time of blood draw. Multivariable linear regression was used to calculate the percentage difference of biomarker concentrations comparing coffee drinkers with nondrinkers, after adjusting for a variety of demographic, clinical, and lifestyle factors. RESULTS Compared with nondrinkers, participants who drank ≥4 cups of total coffee/d had lower concentrations of C-peptide (-8.7%), IGFBP-3 (-2.2%), estrone (-6.4%), total estradiol (-5.7%), free estradiol (-8.1%), leptin (-6.4%), CRP (-16.6%), IL-6 (-8.1%), and sTNFR-2 (-5.8%) and higher concentrations of SHBG (5.0%), total testosterone (7.3% in women and 5.3% in men), total adiponectin (9.3%), and HMW adiponectin (17.2%). The results were largely similar for caffeinated and decaffeinated coffee. CONCLUSION Our data indicate that coffee consumption is associated with favorable profiles of numerous biomarkers in key metabolic and inflammatory pathways. This trial was registered at clinicaltrials.gov as NCT03419455.
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Pre-diagnosis plasma immune markers and risk of non-Hodgkin lymphoma in two prospective cohort studies.
Epstein, MM, Rosner, B, Breen, EC, Batista, JL, Giovannucci, EL, Magpantay, L, Aster, JC, Rodig, SJ, Bertrand, KA, Laden, F, et al
Haematologica. 2018;(10):1679-1687
Abstract
Inflammation and B-cell hyperactivation have been associated with non-Hodgkin lymphoma development. This prospective analysis aimed to further elucidate pre-diagnosis plasma immune marker profiles associated with non-Hodgkin lymphoma risk. We identified 598 incident lymphoma cases and 601 matched controls in Nurses' Health Study and Health Professionals Follow-up Study participants with archived pre-diagnosis plasma samples and measured 13 immune marker levels with multiplexed immunoassays. Using multivariable logistic regression we calculated Odds Ratios (OR) and 95% Confidence Intervals (CI) per standard deviation unit increase in biomarker concentration for risk of non-Hodgkin lymphoma and major histological subtype, stratifying additional models by years (<5, 5 to <10, ≥10) after blood draw. Soluble interleukin-2 receptor-α, CXC chemokine ligand 13, soluble CD30, and soluble tumor necrosis factor receptor-2 were individually positively associated, and B-cell activating factor of the tumor necrosis factor family inversely associated, with all non-Hodgkin lymphoma and one or more subtypes. The biomarker combinations associated independently with lymphoma varied somewhat by subtype and years after blood draw. Of note, the unexpected inverse association between B-cell activating factor and chronic lymphocytic leukemia/small lymphocytic lymphoma risk (OR: 95%CI: 0.51, 0.43-0.62) persisted more than ten years after blood draw (OR: 0.70; 95%CI: 0.52-0.93). In conclusion, immune activation precedes non-Hodgkin lymphoma diagnosis by several years. Decreased B-cell activating factor levels may denote nascent chronic lymphocytic leukemia many years pre-diagnosis.
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An Empirical Dietary Inflammatory Pattern Score Is Associated with Circulating Inflammatory Biomarkers in a Multi-Ethnic Population of Postmenopausal Women in the United States.
Tabung, FK, Giovannucci, EL, Giulianini, F, Liang, L, Chandler, PD, Balasubramanian, R, Manson, JE, Cespedes Feliciano, EM, Hayden, KM, Van Horn, L, et al
The Journal of nutrition. 2018;(5):771-780
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BACKGROUND The empirical dietary inflammatory pattern (EDIP) score has been associated with concentrations of circulating inflammatory biomarkers in European Americans. OBJECTIVE We used the EDIP score, a weighted sum of 18 food groups that characterizes dietary inflammatory potential based on circulating concentrations of inflammatory biomarkers, to test the hypothesis that a pro-inflammatory dietary pattern is associated with inflammatory biomarker concentrations in a US multi-ethnic population. METHODS In this cross-sectional study, we calculated EDIP scores using baseline food frequency questionnaire data from 31,472 women, aged 50-79 y, in the Women's Health Initiative observational study and clinical trials. Circulating biomarkers outcomes at baseline were: C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor (TNF)-α, TNF receptor (TNFR) 1 and 2, and adiponectin. We used multivariable-adjusted linear regression analyses to estimate absolute concentrations and relative differences in biomarker concentrations, overall and in subgroups of race/ethnicity and BMI (body mass index) categories. RESULTS Independent of energy intake, BMI, physical activity, and other potential confounding variables, higher EDIP scores were significantly associated with higher (lower for adiponectin) absolute concentrations of all 6 biomarkers. On the relative scale, the percentage of difference in the concentration of biomarkers, among women in the highest compared to the lowest EDIP quintile, was: CRP, +13% (P-trend < 0.0001); IL-6, +15% (P-trend < 0.0001); TNF-α, +7% (P-trend = 0.0007); TNFR1, +4% (P-trend = 0.0009); TNFR2, +5% (P-trend < 0.0001); and adiponectin, -13% (P-trend <0.0001). These associations differed by racial/ethnic groups and by BMI categories. Whereas the absolute biomarker concentrations were lower among European-American women and among normal-weight women, the associations with diet were stronger than among women of African-American or Hispanic/Latino origin and among overweight and obese women. CONCLUSIONS Findings demonstrate the successful replication of an empirical hypothesis-oriented a posteriori dietary pattern score in a multi-ethnic population of postmenopausal women, with subgroup differences by race/ethnicity and body weight. Future research needs to apply the score in non-US populations.
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Effects of Vitamin D Supplementation on C-peptide and 25-hydroxyvitamin D Concentrations at 3 and 6 Months.
Chandler, PD, Giovannucci, EL, Scott, JB, Bennett, GG, Ng, K, Chan, AT, Hollis, BW, Rifai, N, Emmons, KM, Fuchs, CS, et al
Scientific reports. 2015;:10411
Abstract
The link between African-Americans' disproportionate rates of diabetes, obesity and vitamin D deficiency may be marked by C-peptide as an indicator of insulin secretion. We hypothesize that vitamin D supplementation will increase C-peptide, a marker of insulin secretion. During 3 winters from 2007-2010, 328 healthy African-Americans (median age, 51 years) living in Boston, MA were randomized into a 4-arm, double-blind trial for 3 months of placebo, 1000, 2000, or 4000 IU of vitamin D3. The differences in non-fasting C-peptide between baseline and 3 months were -0.44 ng/mL for those receiving placebo, -0.10 ng/mL for those receiving 1000 IU/d, 0 ng/mL for those receiving 2000 IU/d, 1.24 ng/mL for those receiving 4000 IU/d (C-peptide increased 0.42 ng/mL for each additional 1000 IU/d of vitamin D3, p < 0.001). Vitamin D supplementation increased C-peptide in overweight African-Americans and may be compatible with other recommendations for diabetes prevention and management including weight loss and increased physical activity.
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Vitamin D intake and risk of cardiovascular disease in US men and women.
Sun, Q, Shi, L, Rimm, EB, Giovannucci, EL, Hu, FB, Manson, JE, Rexrode, KM
The American journal of clinical nutrition. 2011;(2):534-42
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BACKGROUND Although studies have linked vitamin D deficiency to an increased risk of cardiovascular disease (CVD), evidence regarding whether vitamin D intake from foods or supplements is prospectively associated with lower CVD risk in healthy humans is limited and inconclusive. OBJECTIVE The objective was to comprehensively evaluate the associations between both dietary and supplemental vitamin D and CVD risk. DESIGN In the Nurses' Health Study (1984-2006) and the Health Professionals Follow-Up Study (1986-2006)-consisting of 74,272 women and 44,592 men, respectively, who were free of CVD and cancer at baseline-we prospectively examined the association between vitamin D intake and incident CVD. RESULTS Over a total of 2,280,324 person-years of follow-up, we identified 9886 incident cases of coronary heart disease and stroke. After multivariate adjustment for age and other CVD risk factors, a higher total vitamin D intake (from foods and supplements) was associated with a decreased risk of CVD in men but not in women; the relative risks (95% CIs) for a comparison of participants who met the Dietary Reference Intake of vitamin D (≥600 IU/d) with participants whose vitamin D intake was <100 IU/d were 0.84 (0.72, 0.97; P for trend = 0.009) for men and 1.02 (0.89, 1.17; P for trend = 0.12) for women. CONCLUSIONS These observations suggest that a higher intake of vitamin D is associated with a lower risk of CVD in men but not in women. Further research is needed to confirm these findings and to elucidate a biological basis for potential sex differences.