Publications by authors named "Andrew T Chan"

567 Publications

Plant-Based Diet Index and Metabolic Risk in Men: Exploring the Role of the Gut Microbiome.

J Nutr 2021 Jun 10. Epub 2021 Jun 10.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: Healthy plant-based diet index (hPDI) is associated with a lower risk of cardiometabolic conditions, but its association as well as interactions with microbiome have not been elucidated.

Objectives: We aimed to investigate the interrelations between hPDI, gut microbiome, and cardiometabolic risk markers.

Methods: hPDI was derived from dietary assessments by a validated FFQ and was examined in relation to metagenomic profiles of 911 fecal samples collected from 303 men aged 71 ± 4 y with an average BMI (in kg/m2) of 25.2 ± 3.6 in the Men's Lifestyle Validation Study. Principal coordinate (PCo) analysis based on Bray-Curtis dissimilarity was conducted, and interactions between hPDI and PCo were examined by using a metabolic risk score composed of blood lipids, BMI, and glycated hemoglobin.

Results: After multivariable adjustment, hPDI was significantly associated with the relative abundance of 7 species and 9 pathways. In particular, higher hPDI was significantly associated with a higher relative abundance of Bacteroides cellulosilyticus and Eubacterium eligens, amino acid biosynthesis pathways (l-isoleucine biosynthesis I and III and l-valine biosynthesis), and the pathway of pyruvate fermentation to isobutanol. A favorable association between hPDI and the metabolic risk score was more pronounced among men with a higher PCo characterized by higher abundance of Bacteroides uniformis and lower abundance of Prevotella copri. At the individual species level, a similar interaction was also observed between hPDI and P. copri, as well as with Clostridium clostridioforme or Blautia hydrogenotrophica (all P-interaction < 0.01).

Conclusion: A greater adherence to a healthy plant-based diet by older men was associated with a microbial profile characterized by a higher abundance of multiple species, including B. cellulosilyticus and E. eligens, as well as pathways in amino acid metabolism and pyruvate fermentation. In addition, inverse associations between healthy plant-based diet and human metabolic risk may partially depend on microbial compositions.
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http://dx.doi.org/10.1093/jn/nxab175DOI Listing
June 2021

Nongenetic Determinants of Risk for Early-Onset Colorectal Cancer.

JNCI Cancer Spectr 2021 Jun 20;5(3):pkab029. Epub 2021 May 20.

Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.

Background: Incidence of early-onset (younger than 50 years of age) colorectal cancer (CRC) is increasing in many countries. Thus, elucidating the role of traditional CRC risk factors in early-onset CRC is a high priority. We sought to determine whether risk factors associated with late-onset CRC were also linked to early-onset CRC and whether association patterns differed by anatomic subsite.

Methods: Using data pooled from 13 population-based studies, we studied 3767 CRC cases and 4049 controls aged younger than 50 years and 23 437 CRC cases and 35 311 controls aged 50 years and older. Using multivariable and multinomial logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to assess the association between risk factors and early-onset CRC and by anatomic subsite.

Results: Early-onset CRC was associated with not regularly using nonsteroidal anti-inflammatory drugs (OR = 1.43, 95% CI = 1.21 to 1.68), greater red meat intake (OR = 1.10, 95% CI = 1.04 to 1.16), lower educational attainment (OR = 1.10, 95% CI = 1.04 to 1.16), alcohol abstinence (OR = 1.23, 95% CI = 1.08 to 1.39), and heavier alcohol use (OR = 1.25, 95% CI = 1.04 to 1.50). No factors exhibited a greater excess in early-onset compared with late-onset CRC. Evaluating risks by anatomic subsite, we found that lower total fiber intake was linked more strongly to rectal (OR = 1.30, 95% CI = 1.14 to 1.48) than colon cancer (OR = 1.14, 95% CI = 1.02 to 1.27;  = .04).

Conclusion: In this large study, we identified several nongenetic risk factors associated with early-onset CRC, providing a basis for targeted identification of those most at risk, which is imperative in mitigating the rising burden of this disease.
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http://dx.doi.org/10.1093/jncics/pkab029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134523PMC
June 2021

Association of bowel movement frequency and laxative use with risk of hepatocellular carcinoma in US women and men.

Int J Cancer 2021 May 24. Epub 2021 May 24.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Abnormal bowel movements have been related to a variety of hepatocellular carcinoma (HCC) risk factors such as dyslipidemia, diabetes and altered metabolism of bile acids and gut microbiota. However, little is known about whether bowel movement frequency affects the risk of developing HCC. We followed 88 123 women in the Nurses' Health Study (NHS) and 28 824 men in the Health Professionals Follow-up Study (HPFS) for up to 24 years. The Cox proportional hazards regression model was used to calculate multivariable hazard ratios (HRs) and confidence intervals (95%CI). We documented 101 incident HCC cases. Compared to those with daily bowel movements, participants with bowel movement more than once per day had a multivariable HR of 1.93 (95%CI: 1.18 to 3.16) in the pooled cohorts. For the same comparison, the positive association appeared stronger for men (2.72, 95% CI: 1.14 to 6.44) than for women (1.63, 95% CI: 0.87 to 3.06) but there was no statistically significant heterogeneity by sex (P-value = .31). We found null associations between bowel movement every 2 days or less and the risk of HCC (HR = 1.05, 95%CI: 0.62 to 1.79). The HR (95%CI) for participants who used laxatives regularly relative to those who never used laxatives was 1.00 (0.64 to 1.55). Our results suggest participants with bowel movement more than once daily is associated with a higher risk of developing HCC compared to those with daily bowel movements. These findings need to be confirmed and potential mechanisms underlying this association need to be elucidated.
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http://dx.doi.org/10.1002/ijc.33699DOI Listing
May 2021

Long-term Intake of Gluten and Cognitive Function Among US Women.

JAMA Netw Open 2021 May 3;4(5):e2113020. Epub 2021 May 3.

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston.

Importance: Gluten avoidance has been suggested as having a benefit to cognitive health among the general population, given the link between gluten and cognitive impairment in patients with celiac disease. However, data are lacking in individuals without celiac disease.

Objective: To examine whether gluten intake is associated with cognitive function in women without celiac disease.

Design, Setting, And Participants: This cohort study included US women who participated in the longitudinal, population-based Nurses' Health Study II and had not previously or subsequently been diagnosed with celiac disease. Dietary data were collected from 1991 to 2015, and data on cognitive function were collected from 2014 to 2019. Data analysis was conducted from October 2020 to April 2021.

Exposures: Energy-adjusted gluten intake, cumulatively averaged across questionnaire cycles prior to cognitive assessment.

Main Outcomes And Measures: Three standardized cognitive scores assessed by the validated Cogstate Brief Battery: (1) psychomotor speed and attention score, (2) learning and working memory score, and (3) global cognition score. Higher scores indicated better performance.

Results: The cohort included 13 494 women (mean [SD] age, 60.6 [4.6] years). The mean (SD) gluten intake was 6.3 (1.6) g/d. After controlling for demographic and lifestyle risk factors in linear regression, no significant differences in standardized cognitive scores (mean [SD], 0 [1]) by quintile of gluten intake were found across highest and lowest quintiles of gluten intake (psychomotor speed and attention: -0.02; 95% CI, -0.07 to 0.03; P for trend = .22; learning and working memory: 0.02; 95% CI, -0.03 to 0.07; P for trend = .30; global cognition: -0.002; 95% CI, -0.05 to 0.05; P for trend = .78). The null associations persisted after additional adjustment for major sources of dietary gluten (ie, refined grains or whole grains), comparing decile categories of gluten intake, using gluten intake updated at each previous questionnaire cycle, or modeling changes in gluten intake. Similarly, these associations were not materially altered in sensitivity analyses that excluded women who had reported cancer or dementia diagnosis or had not completed all dietary assessments.

Conclusions And Relevance: In this study, long-term gluten intake was not associated with cognitive scores in middle-aged women without celiac disease. Our results do not support recommendations to restrict dietary gluten to maintain cognitive function in the absence of celiac disease or established gluten sensitivity.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.13020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140370PMC
May 2021

Association of Screening Lower Endoscopy With Colorectal Cancer Incidence and Mortality in Adults Older Than 75 Years.

JAMA Oncol 2021 May 20. Epub 2021 May 20.

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston.

Importance: Evidence indicates that screening for colorectal cancer (CRC) beginning at 50 years of age can detect early-stage CRC and premalignant neoplasms (eg, adenomas) and thus prevent CRC-related mortality. At present, the US Preventive Services Task Force recommends continuing CRC screening until 75 years of age and individualized decision-making for adults older than 75 years, while accounting for a patient's overall health and screening history. However, scant data exist to support these recommendations.

Objective: To examine the association of lower gastrointestinal tract screening endoscopy with the risk of CRC incidence and CRC-related mortality in older US adults.

Design, Setting, And Participants: This prospective cohort study of health care professionals in the US included data from the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS) from January 1, 1988, through January 31, 2016, for the HPFS and June 30, 2016, for the NHS. Data were analyzed from May 8, 2019, to July 9, 2020.

Exposures: History of screening sigmoidoscopy or colonoscopy (routine/average risk or positive family history) to 75 years of age and after 75 years of age, assessed every 2 years.

Main Outcomes And Measures: Incidence of CRC and CRC-related mortality confirmed by National Death Index, medical records, and pathology reports.

Results: Among 56 374 participants who reached 75 years of age during follow-up (36.8% men and 63.2% women), 661 incident CRC cases and 323 CRC-related deaths were documented. Screening endoscopy after 75 years of age was associated with reduced risk of CRC incidence (multivariable hazard ratio [HR], 0.61; 95% CI, 0.51-0.74) and CRC-related mortality (HR, 0.60; 95% CI, 0.46-0.78), regardless of screening history. The HR comparing screening with nonscreening after 75 years of age was 0.67 (95% CI, 0.50-0.89) for CRC incidence and 0.58 (95% CI, 0.38-0.87) for CRC-related mortality among participants who underwent screening endoscopy before 75 years of age, and 0.51 (95% CI, 0.37-0.70) for CRC incidence and 0.63 (95% CI, 0.43-0.93) for CRC-related mortality among participants without a screening history. However, screening endoscopy after 75 years of age was not associated with risk reduction in CRC death among participants with cardiovascular disease (HR, 1.18; 95% CI, 0.59-2.35) or significant comorbidities (HR, 1.17; 95% CI, 0.57-2.43).

Conclusions And Relevance: In this cohort study, endoscopy among individuals older than 75 years was associated with lower risk of CRC incidence and CRC-related mortality. These data support continuation of screening after 75 years of age among individuals without significant comorbidities.
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http://dx.doi.org/10.1001/jamaoncol.2021.1364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138747PMC
May 2021

Genetically Predicted Circulating C-Reactive Protein Concentration and Colorectal Cancer Survival: A Mendelian Randomization Consortium Study.

Cancer Epidemiol Biomarkers Prev 2021 May 10. Epub 2021 May 10.

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Background: A positive association between circulating C-reactive protein (CRP) and colorectal cancer survival was reported in observational studies, which are susceptible to unmeasured confounding and reverse causality. We used a Mendelian randomization approach to evaluate the association between genetically predicted CRP concentrations and colorectal cancer-specific survival.

Methods: We used individual-level data for 16,918 eligible colorectal cancer cases of European ancestry from 15 studies within the International Survival Analysis of Colorectal Cancer Consortium. We calculated a genetic-risk score based on 52 CRP-associated genetic variants identified from genome-wide association studies. Because of the non-collapsibility of hazard ratios from Cox proportional hazards models, we used the additive hazards model to calculate hazard differences (HD) and 95% confidence intervals (CI) for the association between genetically predicted CRP concentrations and colorectal cancer-specific survival, overall and by stage at diagnosis and tumor location. Analyses were adjusted for age at diagnosis, sex, body mass index, genotyping platform, study, and principal components.

Results: Of the 5,395 (32%) deaths accrued over up to 10 years of follow-up, 3,808 (23%) were due to colorectal cancer. Genetically predicted CRP concentration was not associated with colorectal cancer-specific survival (HD, -1.15; 95% CI, -2.76 to 0.47 per 100,000 person-years; = 0.16). Similarly, no associations were observed in subgroup analyses by stage at diagnosis or tumor location.

Conclusions: Despite adequate power to detect moderate associations, our results did not support a causal effect of circulating CRP concentrations on colorectal cancer-specific survival.

Impact: Future research evaluating genetically determined levels of other circulating inflammatory biomarkers (i.e., IL6) with colorectal cancer survival outcomes is needed.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1848DOI Listing
May 2021

Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women.

Gut 2021 May 6. Epub 2021 May 6.

Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA

Objective: Sugar-sweetened beverage (SSB) consumption had substantially increased across successive US birth cohorts until 2000, and adolescents and young adults under age 50 years have the highest consumption. However, the link between SSBs and early-onset colorectal cancer (EO-CRC) remains unexamined.

Design: In the Nurses' Health Study II (1991-2015), we prospectively investigated the association of SSB intake in adulthood and adolescence with EO-CRC risk among 95 464 women who had reported adulthood beverage intake using validated food frequency questionnaires (FFQs) every 4 years. A subset of 41 272 participants reported beverage intake at age 13-18 years using a validated high school-FFQ in 1998. Cox proportional hazards models were used to estimate relative risks (RRs) with 95% CIs.

Results: We documented 109 EO-CRC cases. Compared with individuals who consumed <1 serving/week of SSBs in adulthood, women who consumed ≥2 servings/day had a more than doubled risk of EO-CRC (RR 2.18; 95% CI 1.10 to 4.35; p=0.02), with a 16% higher risk (RR 1.16; 95% CI 1.00 to 1.36) per serving/day increase. Each serving/day increment of SSB intake at age 13-18 years was associated with a 32% higher risk of EO-CRC (RR 1.32; 95% CI 1.00 to 1.75). Replacing each serving/day of adulthood SSB intake with that of artificially sweetened beverages, coffee, reduced fat milk or total milk was associated with a 17%-36% lower risk of EO-CRC.

Conclusion: Higher SSB intake in adulthood and adolescence was associated with a higher risk of EO-CRC among women. Reduction of SSB consumption among adolescents and young adults may serve as a potential strategy to alleviate the growing burden of EO-CRC.
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http://dx.doi.org/10.1136/gutjnl-2020-323450DOI Listing
May 2021

Risk prediction models for colorectal cancer: Evaluating the discrimination due to added biomarkers.

Int J Cancer 2021 May 5. Epub 2021 May 5.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

Most risk prediction models for colorectal cancer (CRC) are based on questionnaires and show a modest discriminatory ability. Therefore, we aim to develop risk prediction models incorporating plasma biomarkers for CRC to improve discrimination. We assessed the predictivity of 11 biomarkers in 736 men in the Health Professionals Follow-up Study and 639 women in the Nurses' Health Study. We used stepwise logistic regression to examine whether a set of biomarkers improved the predictivity on the basis of predictors in the National Cancer Institute's (NCI) Colorectal Cancer Risk Assessment Tool. Model discrimination was assessed using C-statistics. Bootstrap with 500 randomly sampled replicates was used for internal validation. The models containing each biomarker generated a C-statistic ranging from 0.50 to 0.59 in men and 0.50 to 0.54 in women. The NCI model demonstrated a C-statistic (95% CI) of 0.67 (0.62-0.71) in men and 0.58 (0.54-0.63) in women. Through stepwise selection of biomarkers, the C-statistic increased to 0.70 (0.66-0.74) in men after adding growth/differentiation factor 15, total adiponectin, sex hormone binding globulin and tumor necrosis factor receptor superfamily member 1B (P for difference = 0.008); and increased to 0.62 (0.57-0.66) in women after further including insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 (P for difference = .06). The NCI + selected biomarkers model was internally validated with a C-statistic (95% CI) of 0.73 (0.70-0.77) in men and 0.66 (0.61-0.70) in women. Circulating plasma biomarkers may improve the performance of risk factor-based prediction model for CRC.
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http://dx.doi.org/10.1002/ijc.33621DOI Listing
May 2021

Prognostic significance of myeloid immune cells and their spatial distribution in the colorectal cancer microenvironment.

J Immunother Cancer 2021 Apr;9(4)

Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA

Background: Myeloid cells represent an abundant yet heterogeneous cell population in the colorectal cancer microenvironment, and their roles remain poorly understood.

Methods: We used multiplexed immunofluorescence combined with digital image analysis to identify CD14 monocytic and CD15 granulocytic cells and to evaluate their maturity (HLA-DR and CD33), immunosuppressive potential (ARG1) and proximity to cytokeratin (KRT)-positive tumor cells in 913 colorectal carcinomas. Using covariate data of 4465 incident colorectal cancers in two prospective cohort studies, the inverse probability weighting method was used with multivariable-adjusted Cox proportional hazards models to assess cancer-specific mortality according to ordinal quartiles (Q1-Q4) of myeloid cell densities. Immune cell-tumor cell proximity was measured with the nearest neighbor method and the G-cross function, which determines the likelihood of any tumor cell having at least one immune cell of the specified type within a certain radius.

Results: Higher intraepithelial (=0.0002; HR for Q4 (vs Q1), 0.48, 95% CI 0.31 to 0.76) and stromal ( <0.0001; HR for Q4 (vs Q1), 0.42, 95% CI 0.29 to 0.63) densities of CD14HLA-DR cells were associated with lower colorectal cancer-specific mortality while, conversely, higher intraepithelial densities of CD14HLA-DR cells were associated with higher colorectal cancer-specific mortality (=0.0003; HR for Q4 (vs Q1), 1.78, 95% CI 1.25 to 2.55). Spatial analyses indicated that CD15 cells were located closer to tumor cells than CD14 cells, and CD14HLA-DR cells were closer to tumor than CD14HLA-DR cells (p<0.0001). The G-cross proximity measurement, evaluating the difference in the likelihood of any tumor cell being colocated with at least one CD14HLA-DR cell versus CD14HLA-DR cell within a 20 µm radius, was associated with lower colorectal cancer-specific mortality ( <0.0001; HR for Q4 (vs Q1), 0.37, 95% CI 0.24 to 0.57).

Conclusions: Myeloid cell populations occur in spatially distinct distributions and exhibit divergent, subset-specific prognostic significance in colorectal cancer, with mature CD14HLA-DR and immature CD14HLA-DR monocytic phenotypes most notably showing opposite associations. These results highlight the prognostic utility of multimarker evaluation of myeloid cell infiltrates and reveal a previously unrecognized degree of spatial organization for myeloid cells in the immune microenvironment.
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http://dx.doi.org/10.1136/jitc-2020-002297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098931PMC
April 2021

Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study.

Lancet Infect Dis 2021 Apr 27. Epub 2021 Apr 27.

Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.

Background: The Pfizer-BioNTech (BNT162b2) and the Oxford-AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccines have shown excellent safety and efficacy in phase 3 trials. We aimed to investigate the safety and effectiveness of these vaccines in a UK community setting.

Methods: In this prospective observational study, we examined the proportion and probability of self-reported systemic and local side-effects within 8 days of vaccination in individuals using the COVID Symptom Study app who received one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine. We also compared infection rates in a subset of vaccinated individuals subsequently tested for SARS-CoV-2 with PCR or lateral flow tests with infection rates in unvaccinated controls. All analyses were adjusted by age (≤55 years vs >55 years), sex, health-care worker status (binary variable), obesity (BMI <30 kg/mvs ≥30 kg/m), and comorbidities (binary variable, with or without comorbidities).

Findings: Between Dec 8, and March 10, 2021, 627 383 individuals reported being vaccinated with 655 590 doses: 282 103 received one dose of BNT162b2, of whom 28 207 received a second dose, and 345 280 received one dose of ChAdOx1 nCoV-19. Systemic side-effects were reported by 13·5% (38 155 of 282 103) of individuals after the first dose of BNT162b2, by 22·0% (6216 of 28 207) after the second dose of BNT162b2, and by 33·7% (116 473 of 345 280) after the first dose of ChAdOx1 nCoV-19. Local side-effects were reported by 71·9% (150 023 of 208 767) of individuals after the first dose of BNT162b2, by 68·5% (9025 of 13 179) after the second dose of BNT162b2, and by 58·7% (104 282 of 177 655) after the first dose of ChAdOx1 nCoV-19. Systemic side-effects were more common (1·6 times after the first dose of ChAdOx1 nCoV-19 and 2·9 times after the first dose of BNT162b2) among individuals with previous SARS-CoV-2 infection than among those without known past infection. Local effects were similarly higher in individuals previously infected than in those without known past infection (1·4 times after the first dose of ChAdOx1 nCoV-19 and 1·2 times after the first dose of BNT162b2). 3106 of 103 622 vaccinated individuals and 50 340 of 464 356 unvaccinated controls tested positive for SARS-CoV-2 infection. Significant reductions in infection risk were seen starting at 12 days after the first dose, reaching 60% (95% CI 49-68) for ChAdOx1 nCoV-19 and 69% (66-72) for BNT162b2 at 21-44 days and 72% (63-79) for BNT162b2 after 45-59 days.

Interpretation: Systemic and local side-effects after BNT162b2 and ChAdOx1 nCoV-19 vaccination occur at frequencies lower than reported in phase 3 trials. Both vaccines decrease the risk of SARS-CoV-2 infection after 12 days.

Funding: ZOE Global, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, UK Medical Research Council, Wellcome Trust, UK Research and Innovation, American Gastroenterological Association.
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http://dx.doi.org/10.1016/S1473-3099(21)00224-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078878PMC
April 2021

Tumor Long Interspersed Nucleotide Element-1 (LINE-1) Hypomethylation in Relation to Age of Colorectal Cancer Diagnosis and Prognosis.

Cancers (Basel) 2021 Apr 22;13(9). Epub 2021 Apr 22.

Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Evidence indicates the pathogenic role of epigenetic alterations in early-onset colorectal cancers diagnosed before age 50. However, features of colorectal cancers diagnosed at age 50-54 (hereafter referred to as "intermediate-onset") remain less known. We hypothesized that tumor long interspersed nucleotide element-1 (LINE-1) hypomethylation might be increasingly more common with decreasing age of colorectal cancer diagnosis. In 1356 colorectal cancers, including 28 early-onset and 66 intermediate-onset cases, the tumor LINE-1 methylation level measured by bisulfite-PCR-pyrosequencing (scaled 0 to 100) showed a mean of 63.6 (standard deviation (SD) 10.1). The mean tumor LINE-1 methylation level decreased with decreasing age (mean 64.7 (SD 10.4) in age ≥70, 62.8 (SD 9.4) in age 55-69, 61.0 (SD 10.2) in age 50-54, and 58.9 (SD 12.0) in age <50; < 0.0001). In linear regression analysis, the multivariable-adjusted β coefficient (95% confidence interval (CI)) (vs. age ≥70) was -1.38 (-2.47 to -0.30) for age 55-69, -2.82 (-5.29 to -0.34) for age 50-54, and -4.54 (-8.24 to -0.85) for age <50 ( = 0.0003). Multivariable-adjusted hazard ratios (95% CI) for LINE-1 methylation levels of ≤45, 45-55, and 55-65 (vs. >65) were 2.33 (1.49-3.64), 1.39 (1.05-1.85), and 1.29 (1.02-1.63), respectively ( = 0.0005). In conclusion, tumor LINE-1 hypomethylation is increasingly more common with decreasing age of colorectal cancer diagnosis, suggesting a role of global DNA hypomethylation in colorectal cancer arising in younger adults.
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http://dx.doi.org/10.3390/cancers13092016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122644PMC
April 2021

Body weight variability and the risk of cardiovascular outcomes in patients with nonalcoholic fatty liver disease.

Sci Rep 2021 Apr 28;11(1):9154. Epub 2021 Apr 28.

Division of Gastroenterology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam, 13496, Republic of Korea.

We investigated the association between body weight variability and the risks of cardiovascular disease and mortality in patients with nonalcoholic fatty liver disease (NAFLD) using large-scale, nationwide cohort data. We included 726,736 individuals with NAFLD who underwent a health examination between 2009 and 2010. NAFLD was defined as a fatty liver index ≥ 60, after excluding significant alcohol intake, viral hepatitis, and liver cirrhosis. Body weight variability was assessed using four indices, including variability independent of the mean (VIM). During a median 8.1-year follow-up, we documented 11,358, 14,714, and 22,164 cases of myocardial infarction (MI), stroke, and all-cause mortality, respectively. Body weight variability was associated with an increased risk of MI, stroke, and mortality after adjusting for confounding variables. The hazard ratios (HRs) (95% confidence intervals) for the highest quartile, compared with the lowest quartile, of VIM for body weight were 1.15 (1.10-1.20), 1.22 (1.18-1.26), and 1.56 (1.53-1.62) for MI, stroke, and all-cause mortality, respectively. Body weight variability was associated with increased risks of MI, stroke, and all-cause mortality in NAFLD patients. Appropriate interventions to maintain a stable weight could positively affect health outcomes in NAFLD patients.
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http://dx.doi.org/10.1038/s41598-021-88733-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080815PMC
April 2021

Overview of the Microbiome Among Nurses study (Micro-N) as an example of prospective characterization of the microbiome within cohort studies.

Nat Protoc 2021 Jun 21;16(6):2724-2731. Epub 2021 Apr 21.

Harvard Chan Microbiome in Public Health Center, Harvard T. H. Chan School of Public Health, Boston, MA, USA.

A lack of prospective studies has been a major barrier for assessing the role of the microbiome in human health and disease on a population-wide scale. To address this significant knowledge gap, we have launched a large-scale collection targeting fecal and oral microbiome specimens from 20,000 women within the Nurses' Health Study II cohort (the Microbiome Among Nurses study, or Micro-N). Leveraging the rich epidemiologic data that have been repeatedly collected from this cohort since 1989; the established biorepository of archived blood, urine, buccal cell, and tumor tissue specimens; the available genetic and biomarker data; the cohort's ongoing follow-up; and the BIOM-Mass microbiome research platform, Micro-N furnishes unparalleled resources for future prospective studies to interrogate the interplay between host, environmental factors, and the microbiome in human health. These prospectively collected materials will provide much-needed evidence to infer causality in microbiome-associated outcomes, paving the way toward development of microbiota-targeted modulators, preventives, diagnostics and therapeutics. Here, we describe a generalizable, scalable and cost-effective platform used for stool and oral microbiome specimen and metadata collection in the Micro-N study as an example of how prospective studies of the microbiome may be carried out.
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http://dx.doi.org/10.1038/s41596-021-00519-zDOI Listing
June 2021

Postdiagnostic dairy products intake and colorectal cancer survival in US males and females.

Am J Clin Nutr 2021 Jun;113(6):1636-1646

Department of Nutrition, T. H. Chan School of Public Health, Harvard University, Boston, MA, USA.

Background: To evaluate the association between postdiagnostic dairy intake and survival among patients with colorectal cancer (CRC).

Methods: This study analyzed data from the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). Postdiagnostic dairy intake and other dietary and lifestyle factors were obtained from validated questionnaires. Individual dairy items including milk, cheese, yogurt, and so on were reported, and total, high-fat, and low-fat dairy intakes were derived.

Results: A total of 1753 eligible CRC cases were identified until 2012, from which 703 deaths were documented after a median follow-up time of 8.2 y, and 242 were due to CRC. Overall, when comparing those who consumed 21+ servings/wk with <7 servings/wk, postdiagnostic total dairy intake did not show significant associations with CRC-specific mortality (HR: 1.35; 95% CI: 0.85, 2.13) or overall mortality (HR: 1.28; 95% CI: 0.98, 1.67). However, high-fat dairy, including whole milk and cream cheese, was positively associated with overall mortality (HR: 1.33; 95% CI: 1.08, 1.65) but not significantly with CRC-specific mortality (HR: 1.31; 95% CI: 0.91, 1.90) when comparing those who consumed 10.5+ servings/wk with <3.5 servings/wk. For the same comparison, low-fat dairy, including skim or nonfat milk and cottage cheese, was inversely associated with overall mortality (HR: 0.74; 95% CI: 0.59, 0.92) but not CRC-specific mortality (HR: 0.91; 95% CI: 0.63, 1.29).

Conclusions: Total dairy products intake did not show significant association with CRC-specific or overall mortality. However, high intake of high-fat dairy products was associated with increased mortality, whereas low-fat dairy was associated with lower risk of overall mortality.
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http://dx.doi.org/10.1093/ajcn/nqab059DOI Listing
June 2021

Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study.

Lancet Public Health 2021 05 12;6(5):e335-e345. Epub 2021 Apr 12.

School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.

Background: The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility.

Methods: We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, R, for the two incidence estimates.

Findings: From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6-0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56-0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38-0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the R of B.1.1.7 by a factor of 1·35 (95% CI 1·02-1·69) relative to pre-existing variants. However, R fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant.

Interpretation: The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant.

Funding: Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society.
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http://dx.doi.org/10.1016/S2468-2667(21)00055-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041365PMC
May 2021

Review of Gastroesophageal Reflux Disease.

JAMA 2021 04;325(14):1472

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston.

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http://dx.doi.org/10.1001/jama.2021.1438DOI Listing
April 2021

Postprandial glycaemic dips predict appetite and energy intake in healthy individuals.

Nat Metab 2021 04 12;3(4):523-529. Epub 2021 Apr 12.

Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.

Understanding how to modulate appetite in humans is key to developing successful weight loss interventions. Here, we showed that postprandial glucose dips 2-3 h after a meal are a better predictor of postprandial self-reported hunger and subsequent energy intake than peak glucose at 0-2 h and glucose incremental area under the blood glucose curve at 0-2 h. We explore the links among postprandial glucose, appetite and subsequent energy intake in 1,070 participants from a UK exploratory and US validation cohort, who consumed 8,624 standardized meals followed by 71,715 ad libitum meals, using continuous glucose monitors to record postprandial glycaemia. For participants eating each of the standardized meals, the average postprandial glucose dip at 2-3 h relative to baseline level predicted an increase in hunger at 2-3 h (r = 0.16, P < 0.001), shorter time until next meal (r = -0.14, P < 0.001), greater energy intake at 3-4 h (r = 0.19, P < 0.001) and greater energy intake at 24 h (r = 0.27, P < 0.001). Results were directionally consistent in the US validation cohort. These data provide a quantitative assessment of the relevance of postprandial glycaemia in appetite and energy intake modulation.
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http://dx.doi.org/10.1038/s42255-021-00383-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610681PMC
April 2021

Meeting Report: Translational Advances in Cancer Prevention Agent Development Meeting.

J Cancer Prev 2021 Mar;26(1):71-82

Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland, USA.

The Division of Cancer Prevention of the National Cancer Institute (NCI) and the Office of Disease Prevention of the National Institutes of Health co-sponsored the Translational Advances in Cancer Prevention Agent Development Meeting on August 27 to 28, 2020. The goals of this meeting were to foster the exchange of ideas and stimulate new collaborative interactions among leading cancer prevention researchers from basic and clinical research; highlight new and emerging trends in immunoprevention and chemoprevention as well as new information from clinical trials; and provide information to the extramural research community on the significant resources available from the NCI to promote prevention agent development and rapid translation to clinical trials. The meeting included two plenary talks and five sessions covering the range from pre-clinical studies with chemo/immunopreventive agents to ongoing cancer prevention clinical trials. In addition, two NCI informational sessions describing contract resources for the preclinical agent development and cooperative grants for the Cancer Prevention Clinical Trials Network were also presented.
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http://dx.doi.org/10.15430/JCP.2021.26.1.71DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020174PMC
March 2021

Reply.

Clin Gastroenterol Hepatol 2021 Apr 8. Epub 2021 Apr 8.

Clinical and Translational Epidemiology Unit, Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts.

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http://dx.doi.org/10.1016/j.cgh.2021.04.009DOI Listing
April 2021

Genomic Risk Score for Melanoma in a Prospective Study of Older Individuals.

J Natl Cancer Inst 2021 Apr 10. Epub 2021 Apr 10.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.

Background: Recent genome-wide association meta-analysis for melanoma doubled the number of previously identified variants. We assessed the performance of an updated polygenic risk score (PRS) in a population of older individuals, where melanoma incidence and cumulative ultraviolet radiation exposure is greatest.

Methods: We assessed a PRS for cutaneous melanoma comprising 55 variants in a prospective study of 12,712 individuals in the ASPirin in Reducing Events in the Elderly trial. We evaluated incident melanomas diagnosed during the trial and prevalent melanomas diagnosed pre-enrolment (self-reported). Multivariable models examined associations between PRS as a continuous variable (per standard deviation [SD]), and categorical (low-risk [0-20%], medium-risk [21-80%], high-risk [81-100%] groups) with incident melanoma. Logistic regression examined the association between PRS and prevalent melanoma.

Results: At baseline, mean participant age was 75 years; 55.0% were female, and 528 (4.2%) had prevalent melanomas. During follow-up (median = 4.7 years), 120 (1.0%) incident cutaneous melanomas occurred, 98 of which were in participants with no history. PRS was associated with incident melanoma (hazard ratio = 1.46 per SD, 95% confidence interval [CI] = 1.20-1.77) and prevalent melanoma (odds ratio [OR]=1.55 per SD, 95% CI = 1.42-1.69). Participants in the highest-risk PRS group had increased risk compared to the low-risk group for incident (OR = 2.51, 95% CI = 1.28-4.92) and prevalent (OR = 3.66, 95% CI = 2.69-5.05). When stratifying by sex, only males had an association between the PRS and incident melanoma, whereas both sexes had an association between the PRS and prevalent melanoma.

Conclusion: A genomic risk score is associated with melanoma risk in older individuals, and may contribute to targeted surveillance.
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http://dx.doi.org/10.1093/jnci/djab076DOI Listing
April 2021

Gut microbiota-derived metabolites and risk of coronary artery disease: a prospective study among US men and women.

Am J Clin Nutr 2021 Apr 7. Epub 2021 Apr 7.

Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.

Background: Accumulating evidence has suggested that human gut microbiota metabolize certain dietary compounds and subsequently produce bioactive metabolites that may exert beneficial or harmful effects on coronary artery disease (CAD) risk.

Objectives: This study examined the joint association of 2 gut microbiota metabolites, enterolactone and trimethylamine N-oxide (TMAO), that originate from intake of plant-based foods and animal products, respectively, in relation to CAD risk.

Methods: A prospective nested case-control study of CAD was conducted among participants who were free of diabetes, cardiovascular disease, and cancer in the Nurses' Health Study II and the Health Professionals Follow-up Study. Plasma concentrations of enterolactone and TMAO, as well as choline and L-carnitine, were assayed among 608 CAD case-control pairs.

Results: A high enterolactone and low TMAO profile was associated with better diet quality, especially higher intake of whole grains and fiber and lower intake of red meats, as well as lower concentrations of plasma triglycerides and C-reactive protein. Participants with a high enterolactone/low TMAO profile had a significantly lower risk of CAD: the multivariate-adjusted OR was 0.58 (95% CI: 0.38, 0.90), compared with participants with a low enterolactone/high TMAO profile. No significant interaction between enterolactone and TMAO on CAD risk was observed. Neither TMAO nor enterolactone alone were associated with CAD risk in pooled analyses. In women, a higher enterolactone concentration was significantly associated with a 54% lower CAD risk (P trend = 0.03), although the interaction by sex was not significant.

Conclusions: Our results show that a profile characterized by high enterolactone and low TMAO concentrations in plasma is linked to a healthful dietary pattern and significantly associated with a lower risk of CAD. Overall, these data suggest that, compared with individual markers, multiple microbiota-derived metabolites may facilitate better differentiation of CAD risk and characterization of the relations between diet, microbiota, and CAD risk.
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http://dx.doi.org/10.1093/ajcn/nqab053DOI Listing
April 2021

Aspirin Modulation of the Colorectal Cancer-Associated Microbe Fusobacterium nucleatum.

mBio 2021 04 6;12(2). Epub 2021 Apr 6.

Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA

Aspirin is a chemopreventive agent for colorectal adenoma and cancer (CRC) that, like many drugs inclusive of chemotherapeutics, has been investigated for its effects on bacterial growth and virulence gene expression. Given the evolving recognition of the roles for bacteria in CRC, in this work, we investigate the effects of aspirin with a focus on one oncomicrobe- We show that aspirin and its primary metabolite salicylic acid alter strain Fn7-1 growth in culture and that aspirin can effectively kill both actively growing and stationary Fn7-1. We also demonstrate that, at levels that do not inhibit growth, aspirin influences Fn7-1 gene expression. To assess whether aspirin modulation of may be relevant , we use the mouse intestinal tumor model in which Fn7-1 is orally inoculated daily to reveal that aspirin-supplemented chow is sufficient to inhibit -potentiated colonic tumorigenesis. We expand our characterization of aspirin sensitivity across other strains, including those isolated from human CRC tissues, as well as other CRC-associated microbes, enterotoxigenic , and colibactin-producing Finally, we determine that individuals who use aspirin daily have lower fusobacterial abundance in colon adenoma tissues, as determined by quantitative PCR performed on adenoma DNA. Together, our data support that aspirin has direct antibiotic activity against strains and suggest that consideration of the potential effects of aspirin on the microbiome holds promise in optimizing risk-benefit assessments for use of aspirin in CRC prevention and management. There is an increasing understanding of the clinical correlations and potential mechanistic roles of specific members of the gut and tumoral microbiota in colorectal cancer (CRC) initiation, progression, and survival. However, we have yet to parlay this knowledge into better CRC outcomes through microbially informed diagnostic, preventive, or therapeutic approaches. Here, we demonstrate that aspirin, an established CRC chemopreventive, exhibits specific effects on the CRC-associated in culture, an animal model of intestinal tumorigenesis, and in human colonic adenoma tissues. Our work proposes a potential role for aspirin in influencing CRC-associated bacteria to prevent colorectal adenomas and cancer, beyond aspirin's canonical anti-inflammatory role targeting host tissues. Future research, such as studies investigating the effects of aspirin on fusobacterial load in patients, will help further elucidate the prospect of using aspirin to modulate for improving CRC outcomes.
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http://dx.doi.org/10.1128/mBio.00547-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092249PMC
April 2021

A framework for microbiome science in public health.

Nat Med 2021 05 5;27(5):766-774. Epub 2021 Apr 5.

Harvard Chan Microbiome in Public Health Center, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Human microbiome science has advanced rapidly and reached a scale at which basic biology, clinical translation and population health are increasingly integrated. It is thus now possible for public health researchers, practitioners and policymakers to take specific action leveraging current and future microbiome-based opportunities and best practices. Here we provide an outline of considerations for research, education, interpretation and scientific communication concerning the human microbiome and public health. This includes guidelines for population-scale microbiome study design; necessary physical platforms and analysis methods; integration into public health areas such as epidemiology, nutrition, chronic disease, and global and environmental health; entrepreneurship and technology transfer; and educational curricula. Particularly in the near future, there are both opportunities for the incorporation of microbiome-based technologies into public health practice, and a growing need for policymaking and regulation around related areas such as prebiotic and probiotic supplements, novel live-cell therapies and fecal microbiota transplants.
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http://dx.doi.org/10.1038/s41591-021-01258-0DOI Listing
May 2021

DIETARY GLUTEN INTAKE IS NOT ASSOCIATED WITH RISK OF INFLAMMATORY BOWEL DISEASE IN U.S. ADULTS WITHOUT CELIAC DISEASE.

Clin Gastroenterol Hepatol 2021 Mar 25. Epub 2021 Mar 25.

Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA; Clinical and Translation Epidemiology, Massachusetts General Hospital and Harvard Medical School, Boston MA; Broad Institute of MIT and Harvard, Cambridge MA 02142. Electronic address:

Background & Aims: Diet is thought to play a role in the development of inflammatory bowel disease (IBD), though the relationship between gluten intake and risk of IBD has not been explored. The aim of this study was to determine the relationship between gluten intake and risk of incident Crohn's disease (CD) and ulcerative colitis (UC).

Methods: We performed a prospective cohort study of 208,280 US participants from the Nurses' Health Study (NHS; 1986-2016), NHSII (1991-2017), and Health Professionals Follow-up Study (1986-2016) who did not have IBD at baseline or celiac disease, and who completed semi-quantitative food frequency questionnaires. We used Cox proportional hazards modeling to estimate the risk of IBD according to quintiles of cumulative average energy-adjusted dietary gluten intake over follow-up period.

Results: We documented 337 CD cases and 447 UC cases over 5,115,265 person-years of follow-up. Dietary gluten intake was not associated with risk of IBD. Compared to participants in the lowest quintile of gluten intake, the adjusted hazard-ratios and 95% confidence intervals (CI) for participants in the highest quintile of gluten intake were 1.16 (95% CI: 0.82-1.64; P = 0.41) for CD and 1.04 (95% CI: 0.75-1.44; P = 0.64) for UC. Adjusting for primary sources of gluten intake did not materially change our estimates.

Conclusions: In three large adult US prospective cohorts, gluten intake was not associated with risk of CD or UC. Our findings are reassuring at a time when consumption of gluten has been increasingly perceived as a trigger for chronic gastrointestinal diseases.
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http://dx.doi.org/10.1016/j.cgh.2021.03.029DOI Listing
March 2021

History of Diverticulitis and Risk of Incident Cardiovascular Disease in Men: A Cohort Study.

Dig Dis Sci 2021 Mar 26. Epub 2021 Mar 26.

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA.

Background: Diverticulitis and cardiovascular disease (CVD) are two highly prevalent disorders sharing common risk factors which are hypothesized to have an inflammatory basis.

Aims: To examine the association between history of diverticulitis and risk of incident CVD.

Methods: We conducted a prospective cohort study of 43,904 men aged 40 to 75 years without a history of CVD (fatal or nonfatal myocardial infarction and stroke) at enrollment who were followed up from 1986 to 2012 in the Health Professionals Follow-Up Study. Lifestyle factors, dietary intake, and disease information were self-reported biennially or quadrennially. Incident diverticulitis and CVD were confirmed by review of medical records. We used Cox proportional hazard models to calculate age- and multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) of incident CVD. We conducted a stratified analysis according to the presence or absence of CVD risk factors (smoking, hypertension, hyperlipidemia, and diabetes).

Results: We identified 3848 incident cases of CVD during 856,319 person-years of follow-up. Men with diverticulitis had higher incidence of CVD (727 cases per 100,000 person-years) compared to men without diverticulitis [446 cases per 100,000 person-years, multivariate HR of 1.35 (95% CI 1.07-1.70)]. The association of diverticulitis and subsequent CVD appeared more evident among men without known CVD risk factors (HR 4.06, 95% CI 2.04-8.08) compared to those with one or more CVD risk factors (HR 1.27, 95% CI 0.98-1.63).

Conclusions: Diverticulitis may be an independent risk factor of incident CVD, suggesting possible common etiopathogenic mechanisms. Diagnosis of diverticulitis underscores the importance of preventive measures to reduce future CVD.
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http://dx.doi.org/10.1007/s10620-021-06949-9DOI Listing
March 2021

Symptoms and syndromes associated with SARS-CoV-2 infection and severity in pregnant women from two community cohorts.

Sci Rep 2021 03 25;11(1):6928. Epub 2021 Mar 25.

School of Biomedical Engineering and Imaging Sciences, King's College London, 9th floor, Becket House, 1 Lambeth Palace Road, London, SE1 7EU, UK.

We tested whether pregnant and non-pregnant women differ in COVID-19 symptom profile and severity, and we extended previous investigations on hospitalized pregnant women to those who did not require hospitalization. Two female community-based cohorts (18-44 years) provided longitudinal (smartphone application, N = 1,170,315, n = 79 pregnant tested positive) and cross-sectional (web-based survey, N = 1,344,966, n = 134 pregnant tested positive) data, prospectively collected through self-participatory citizen surveillance in UK, Sweden and USA. Pregnant and non-pregnant were compared for frequencies of events, including SARS-CoV-2 testing, symptoms and hospitalization rates. Multivariable regression was used to investigate symptoms severity and comorbidity effects. Pregnant and non-pregnant women positive for SARS-CoV-2 infection were not different in syndromic severity, except for gastrointestinal symptoms. Pregnant were more likely to have received testing, despite reporting fewer symptoms. Pre-existing lung disease was most closely associated with syndromic severity in pregnant hospitalized. Heart and kidney diseases and diabetes increased risk. The most frequent symptoms among non-hospitalized women were anosmia [63% pregnant, 92% non-pregnant] and headache [72%, 62%]. Cardiopulmonary symptoms, including persistent cough [80%] and chest pain [73%], were more frequent among pregnant who were hospitalized. Consistent with observations in non-pregnant populations, lung disease and diabetes were associated with increased risk of more severe SARS-CoV-2 infection during pregnancy.
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http://dx.doi.org/10.1038/s41598-021-86452-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994587PMC
March 2021

Simple Sugar and Sugar-Sweetened Beverage Intake During Adolescence and Risk of Colorectal Cancer Precursors.

Gastroenterology 2021 Mar 19. Epub 2021 Mar 19.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Background & Aims: Recent increasing trends in early-onset colorectal cancer (CRC) strongly supports that early-life diet is involved in CRC development. However, data are lacking on the relationship with high sugar intake during early life.

Methods: We prospectively investigated the association of adolescent simple sugar (fructose, glucose, added sugar, total sugar) and sugar-sweetened beverage (SSB) intake with CRC precursor risk in 33,106 participants of the Nurses' Health Study II who provided adolescent dietary information in 1998 and subsequently underwent lower gastrointestinal endoscopy between 1999 and 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression for clustered data.

Results: During follow-up, 2909 conventional adenomas (758 high-risk) and 2355 serrated lesions were identified (mean age at diagnoses, 52.2 ± 4.3 years). High sugar and SSB intake during adolescence was positively associated with risk of adenoma, but not serrated lesions. Per each increment of 5% of calories from total fructose intake, multivariable ORs were 1.17 (95% CI, 1.05-1.31) for total and 1.30 (95% CI, 1.06-1.60) for high-risk adenoma. By subsite, ORs were 1.12 (95% CI, 0.96-1.30) for proximal, 1.24 (95% CI, 1.05-1.47) for distal, and 1.43 (95% CI, 1.10-1.86) for rectal adenoma. Per 1 serving/day increment in SSB intake, ORs were 1.11 (95% CI, 1.02-1.20) for total and 1.30 (95% CI, 1.08-1.55) for rectal adenoma. Contrary to adolescent intake, sugar and SSB intake during adulthood was not associated with adenoma risk.

Conclusions: High intake of simple sugars and SSBs during adolescence was associated with increased risk of conventional adenoma, especially rectal adenoma.
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http://dx.doi.org/10.1053/j.gastro.2021.03.028DOI Listing
March 2021

Symptom clusters in COVID-19: A potential clinical prediction tool from the COVID Symptom Study app.

Sci Adv 2021 03 19;7(12). Epub 2021 Mar 19.

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, MA, USA.

As no one symptom can predict disease severity or the need for dedicated medical support in coronavirus disease 2019 (COVID-19), we asked whether documenting symptom time series over the first few days informs outcome. Unsupervised time series clustering over symptom presentation was performed on data collected from a training dataset of completed cases enlisted early from the COVID Symptom Study Smartphone application, yielding six distinct symptom presentations. Clustering was validated on an independent replication dataset between 1 and 28 May 2020. Using the first 5 days of symptom logging, the ROC-AUC (receiver operating characteristic - area under the curve) of need for respiratory support was 78.8%, substantially outperforming personal characteristics alone (ROC-AUC 69.5%). Such an approach could be used to monitor at-risk patients and predict medical resource requirements days before they are required.
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http://dx.doi.org/10.1126/sciadv.abd4177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978420PMC
March 2021