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Association Between Midlife Obesity and Kidney Function Trajectories: The Atherosclerosis Risk in Communities (ARIC) Study.
Yu, Z, Grams, ME, Ndumele, CE, Wagenknecht, L, Boerwinkle, E, North, KE, Rebholz, CM, Giovannucci, EL, Coresh, J
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2021;(3):376-385
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RATIONALE & OBJECTIVE Obesity has been related to risk for chronic kidney disease. However, the associations of different measures of midlife obesity with long-term kidney function trajectories and whether they differ by sex and race are unknown. STUDY DESIGN Observational study. SETTING & PARTICIPANTS 13,496 participants from the Atherosclerosis Risk in Communities (ARIC) Study. PREDICTORS Midlife obesity status as measured by body mass index (BMI), waist-to-hip ratio, and predicted percent fat at baseline. OUTCOMES Estimated glomerular filtration rate (eGFR) calculated using serum creatinine level measured at 5 study visits, and incident kidney failure with replacement therapy (KFRT). ANALYTICAL APPROACH Mixed models with random intercepts and random slopes for eGFR. Cox proportional hazards models for KFRT. RESULTS Baseline mean age was 54 years, median eGFR was 103mL/min/1.73m2, and median BMI was 27kg/m2. Over 30 years of follow-up, midlife obesity measures were associated with eGFR decline in White and Black women but not consistently in men. Adjusted for age, center, smoking, and coronary heart disease, the differences in eGFR slope per 1-SD higher BMI, waist-to-hip ratio, and predicted percent fat were 0.09 (95% CI, -0.18 to 0.36), -0.25 (95% CI, -0.50 to 0.01), and-0.14 (95% CI, -0.41 to 0.13) mL/min/1.73m2 per decade for White men; -0.91 (95% CI, -1.15 to-0.67), -0.82 (95% CI, -1.06 to-0.58), and-1.02 (95% CI, -1.26 to-0.78) mL/min/1.73m2 per decade for White women; -0.70 (95% CI, -1.54 to 0.14), -1.60 (95% CI, -2.42 to-0.78), and-1.24 (95% CI, -2.08 to-0.40) mL/min/1.73m2 per decade for Black men; and-1.24 (95% CI, -2.08 to-0.40), -1.50 (95% CI, -2.05 to-0.95), and-1.43 (95% CI, -2.00 to-0.86) mL/min/1.73m2 per decade for Black women. Obesity indicators were independently associated with risk for KFRT for all sex-race groups except White men. LIMITATIONS Loss to follow-up during 3 decades of follow-up with 5 eGFR assessments. CONCLUSIONS Obesity status is a risk factor for future decline in kidney function and development of KFRT in Black and White women, with less consistent associations among men.
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Total Vitamin D Intake and Risks of Early-Onset Colorectal Cancer and Precursors.
Kim, H, Lipsyc-Sharf, M, Zong, X, Wang, X, Hur, J, Song, M, Wang, M, Smith-Warner, SA, Fuchs, C, Ogino, S, et al
Gastroenterology. 2021;(4):1208-1217.e9
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BACKGROUND & AIMS Vitamin D has been implicated in colorectal cancer (CRC) pathogenesis, but it remains unknown whether total vitamin D intake is associated with early-onset CRC and precursors diagnosed before age 50. METHODS We prospectively examined the association between total vitamin D intake and risks of early-onset CRC and precursors among women enrolled in the Nurses' Health Study II. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for early-onset CRC were estimated with Cox proportional hazards model. Multivariable-adjusted odds ratios (ORs) and 95% CIs for early-onset conventional adenoma and serrated polyp were estimated with logistic regression model. RESULTS We documented 111 incident cases of early-onset CRC during 1,250,560 person-years of follow-up (1991 to 2015). Higher total vitamin D intake was significantly associated with a reduced risk of early-onset CRC (HR for ≥450 IU/day vs <300 IU/day, 0.49; 95% CI, 0.26-0.93; P for trend = .01). The HR per 400 IU/day increase was 0.46 (95% CI, 0.26-0.83). The inverse association was significant and appeared more evident for dietary sources of vitamin D (HR per 400 IU/day increase, 0.34; 95% CI, 0.15-0.79) than supplemental vitamin D (HR per 400 IU/day increase, 0.77; 95% CI, 0.37-1.62). For CRC precursors, the ORs per 400 IU/day increase were 0.76 (95% CI, 0.65-0.88) for conventional adenoma (n = 1,439) and 0.85 (95% CI, 0.75-0.97) for serrated polyp (n = 1,878). CONCLUSIONS In a cohort of younger women, higher total vitamin D intake was associated with decreased risks of early-onset CRC and precursors.
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The Sulfur Microbial Diet Is Associated With Increased Risk of Early-Onset Colorectal Cancer Precursors.
Nguyen, LH, Cao, Y, Hur, J, Mehta, RS, Sikavi, DR, Wang, Y, Ma, W, Wu, K, Song, M, Giovannucci, EL, et al
Gastroenterology. 2021;(5):1423-1432.e4
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BACKGROUND & AIMS Diet may contribute to the increasing incidence of colorectal cancer (CRC) before age 50 (early-onset CRC). Microbial metabolism of dietary sulfur produces hydrogen sulfide (H2S), a gastrointestinal carcinogen that cannot be easily measured at scale. As a result, evidence supporting its role in early neoplasia is lacking. METHODS We evaluated long-term adherence to the sulfur microbial diet, a dietary index defined a priori based on increased abundance of 43 bacterial species involved with sulfur metabolism, with risk of CRC precursors among 59,013 individuals who underwent lower endoscopy in the Nurses' Health Study II (1991-2015), a prospective cohort study with dietary assessment every 4 years through validated food frequency questionnaires and an assessment of dietary intake during adolescence in 1998. The sulfur microbial diet was characterized by intake high in processed meats, foods previously linked to CRC development, and low in mixed vegetables and legumes. Multivariable logistic regression for clustered data was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS We documented 2911 cases of early-onset adenoma. After adjusting for established risk factors, higher sulfur microbial diet scores were associated with increased risk for early-onset adenomas (ORquartile [Q]4 vs Q1, 1.31; 95% CI, 1.10-1.56, Ptrend = .02), but not serrated lesions. Compared with the lowest, women in the highest quartile of sulfur microbial diet scores had significantly increased risk of early-onset adenomas with greater malignant potential (ORQ4 vs Q1, 1.65 for villous/tubulovillous histology; 95% CI, 1.12-2.43; Ptrend = .04). Similar trends for early-onset adenoma were observed based on diet consumed during adolescence. In contrast, no clear association for adenomas was identified after age 50. CONCLUSIONS Our findings in a cohort of young women support a role for dietary interactions with gut sulfur-metabolizing bacteria in early-onset colorectal carcinogenesis, possibly beginning in adolescence.
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Genetic and Circulating Biomarker Data Improve Risk Prediction for Pancreatic Cancer in the General Population.
Kim, J, Yuan, C, Babic, A, Bao, Y, Clish, CB, Pollak, MN, Amundadottir, LT, Klein, AP, Stolzenberg-Solomon, RZ, Pandharipande, PV, et al
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2020;(5):999-1008
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BACKGROUND Pancreatic cancer is the third leading cause of cancer death in the United States, and 80% of patients present with advanced, incurable disease. Risk markers for pancreatic cancer have been characterized, but combined models are not used clinically to identify individuals at high risk for the disease. METHODS Within a nested case-control study of 500 pancreatic cancer cases diagnosed after blood collection and 1,091 matched controls enrolled in four U.S. prospective cohorts, we characterized absolute risk models that included clinical factors (e.g., body mass index, history of diabetes), germline genetic polymorphisms, and circulating biomarkers. RESULTS Model discrimination showed an area under ROC curve of 0.62 via cross-validation. Our final integrated model identified 3.7% of men and 2.6% of women who had at least 3 times greater than average risk in the ensuing 10 years. Individuals within the top risk percentile had a 4% risk of developing pancreatic cancer by age 80 years and 2% 10-year risk at age 70 years. CONCLUSIONS Risk models that include established clinical, genetic, and circulating factors improved disease discrimination over models using clinical factors alone. IMPACT Absolute risk models for pancreatic cancer may help identify individuals in the general population appropriate for disease interception.
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Dietary Inflammatory Potential and Risk of Cardiovascular Disease Among Men and Women in the U.S.
Li, J, Lee, DH, Hu, J, Tabung, FK, Li, Y, Bhupathiraju, SN, Rimm, EB, Rexrode, KM, Manson, JE, Willett, WC, et al
Journal of the American College of Cardiology. 2020;(19):2181-2193
Abstract
BACKGROUND Inflammation plays an important role in cardiovascular disease (CVD) development. Diet modulates inflammation; however, it remains unknown whether dietary patterns with higher inflammatory potential are associated with long-term CVD risk. OBJECTIVES This study sought to examine whether proinflammatory diets are associated with increased CVD risk. METHODS We prospectively followed 74,578 women from the Nurses' Health Study (NHS) (1984-2016), 91,656 women from the NHSII (1991-2015), and 43,911 men from the Health Professionals Follow-up Study (1986-2016) who were free of CVD and cancer at baseline. Diet was assessed by food frequency questionnaires every 4 years. The inflammatory potential of diet was evaluated using a food-based empirical dietary inflammatory pattern (EDIP) score that was pre-defined based on levels of 3 systemic inflammatory biomarkers. RESULTS During 5,291,518 person-years of follow-up, we documented 15,837 incident CVD cases, including 9,794 coronary heart disease (CHD) cases and 6,174 strokes. In pooled analyses of the 3 cohorts, after adjustment for use of anti-inflammatory medications and CVD risk factors including body mass index, a higher dietary inflammatory potential, as indicated by higher EDIP scores, was associated with an increased risk of CVD (hazard ratio [HR] comparing the highest to lowest quintiles: 1.38; 95% confidence interval [CI]: 1.31 to 1.46; p for trend <0.001), CHD (HR: 1.46; 95% CI: 1.36 to 1.56; p for trend <0.001), and stroke (HR: 1.28; 95% CI: 1.17- to 1.39; p for trend <0.001). These associations were consistent across cohorts and between sexes, and they remained significant after further adjustment for other dietary quality indices. In a subset of study participants (n = 33,719), a higher EDIP was associated with a higher circulating profile of proinflammatory biomarkers, lower levels of adiponectin, and an unfavorable blood lipid profile (p < 0.001). CONCLUSIONS Dietary patterns with a higher proinflammatory potential were associated with higher CVD risk. Reducing the inflammatory potential of the diet may potentially provide an effective strategy for CVD prevention.
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Physical Activity and Risk of Hepatocellular Carcinoma Among U.S. Men and Women.
Luo, X, Yang, W, Ma, Y, Simon, TG, Meyerhardt, JA, Chan, AT, Giovannucci, EL, Zhang, X
Cancer prevention research (Philadelphia, Pa.). 2020;(8):707-714
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Mounting evidence indicates a potential beneficial effect of vigorous-intensity physical activity on hepatocellular carcinoma (HCC). However, the association between moderate-intensity physical activity, such as brisk walking, and the risk of HCC remains largely unknown. Two prospective cohorts of 77,535 women from the Nurses' Health Study and 44,540 men from the Health Professionals Follow-up Study were included. Weekly time spent on physical activities were updated biennially. The Cox proportional hazard regression model was used to calculate multivariable hazard ratios (HR) and 95% confidence intervals (95% CI). After an average 23-year follow-up, we identified 138 incident HCC cases. A higher amount of total physical activity was not significantly associated with a reduced risk of HCC (top tertile vs. bottom tertile; HR = 0.78; 95% CI, 0.51-1.18; P trend = 0.33). For the same comparison, there was an inverse association between moderate-intensity activity and HCC risk (HR = 0.60; 95% CI, 0.38-0.94; P trend = 0.04), whereas no statistically significant association with vigorous-intensity activity (HR = 0.88; 95% CI, 0.56-1.37; P trend = 0.74). Engaging in brisk walking was significantly associated with a lower risk of HCC (over 1 hour/week vs. non-brisk walking; HR = 0.50; 95% CI, 0.31-0.78; P trend = 0.006). The association between brisk walking and HCC risk was generally present across all subgroups, including age, body mass index, type 2 diabetes mellitus, smoking status, aspirin use, and alcohol consumption (all P interaction ≥ 0.05). In conclusion, moderate-intensity activity, especially brisk walking, was associated with reduced risk of HCC among U.S. men and women. If confirmed, brisk walking might serve a feasible way for HCC prevention.
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Periodontal Disease, Tooth Loss, and Risk of Serrated Polyps and Conventional Adenomas.
Lo, CH, Nguyen, LH, Wu, K, Ogino, S, Chan, AT, Giovannucci, EL, Song, M
Cancer prevention research (Philadelphia, Pa.). 2020;(8):699-706
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Growing data indicate an association between periodontal disease and the development of cancer. However, the evidence for colorectal cancer has been inconsistent and longitudinal study examining its precursor lesions is lacking. We prospectively collected information on periodontal disease and number of tooth loss in the Nurses' Health Study (1992-2002) and the Health Professionals Follow-up Study (1992-2010). Polyp diagnosis was acquired via self-reported questionnaires and confirmed through review of medical records. We used logistic regression to calculate the multivariate-adjusted ORs and 95% confidence intervals (CI) with adjustment for smoking and other known risk factors for periodontal disease and colorectal cancer. In this study, we included 17,904 women and 24,582 men. We documented 2,336 cases of serrated polyps and 4,102 cases of conventional adenomas among 84,714 person-endoscopies throughout follow-up. The ORs of serrated polyps and conventional adenomas comparing individuals with and without periodontal disease were 1.17 (95% CI, 1.06-1.29) and 1.11 (95% CI, 1.02-1.19), respectively. Compared with participants without tooth loss, those who lost ≥4 teeth had 20% (OR, 1.20; 95% CI, 1.03-1.39) greater risk of serrated polyps (P trend 0.01). Among never smokers, similar associations with periodontal disease were observed for both serrated polyps (OR, 1.20; 95% CI, 1.02-1.41) and conventional adenomas (OR, 1.12; 95% CI, 1.00-1.26). History of periodontal disease and possibly higher number of tooth loss may modestly increase the risk of developing colorectal precursor lesions. Our findings advance our understanding of the interplay between oral health, microbiome, and early colorectal carcinogenesis.
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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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Association between Vitamin D Genetic Risk Score and Cancer Risk in a Large Cohort of U.S. Women.
Chandler, PD, Tobias, DK, Wang, L, Smith-Warner, SA, Chasman, DI, Rose, L, Giovannucci, EL, Buring, JE, Ridker, PM, Cook, NR, et al
Nutrients. 2018;(1)
Abstract
Some observational studies suggest an inverse association between circulating 25-hydroxyvitamin D (25OHD) and cancer incidence and mortality. We conducted a Mendelian randomization analysis of the relationship between a vitamin D genetic risk score (GRS, range 0-10), comprised of five single nucleotide polymorphisms (SNPs) of vitamin D status in the DHCR7, CYP2R1 and GC genes and cancer risk among women. Analysis was performed in the Women's Genome Health Study (WGHS), including 23,294 women of European ancestry who were cancer-free at baseline and followed for 20 years for incident cancer. In a subgroup of 1782 WGHS participants with 25OHD measures at baseline, the GRS was associated with circulating 25OHD mean (SD) = 67.8 (26.1) nmol/L, 56.9 (18.7) nmol/L in the lowest versus 73.2 (27.9) nmol/L in the highest quintile of the GRS (p trend < 0.0001 across quintiles). However, in age-adjusted Cox proportional hazards models, higher GRS (reflecting higher 25OHD levels) was not associated (cases; Hazard Ratio (HR) (95% Confidence Interval (CI)), p-value) with incident total cancer: (n = 3985; 1.01 (1.00-1.03), p = 0.17), breast (n = 1560; 1.02 (0.99-1.05), p = 0.21), colorectal (n = 329; 1.06 (1.00-1.13), p = 0.07), lung (n = 330; 1.00 (0.94-1.06), p = 0.89) or total cancer death (n = 770; 1.00 (0.96-1.04), p = 0.90). Results were similar in fully-adjusted models. A GRS for higher circulating 25OHD was not associated with cancer incidence or mortality.
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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.