Faculty Bibliography
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537
Mediterranean Diet and the Association Between Air Pollution and Cardiovascular Disease Mortality Risk
BACKGROUND:Recent experimental evidence suggests that nutritional supplementation can blunt adverse cardiopulmonary effects induced by acute air pollution exposure. However, whether usual individual dietary patterns can modify the association between long-term air pollution exposure and health outcomes have not been previously investigated. We assessed, in a large cohort with detailed diet information at the individual level, whether a Mediterranean diet modifies the association between long-term exposure to ambient air pollution and cardiovascular disease mortality risk. METHODS:air pollution at the residential census-tract level. The alternative Mediterranean Diet Index (aMED), which uses a 9-point scale to assess conformity with a Mediterranean-style diet, was constructed for each participant from information in cohort baseline dietary questionnaires. We evaluated mortality risks for cardiovascular disease (CVD), ischemic heart disease (IHD), cerebrovascular disease (CER), or cardiac arrest (CAR) associated with long-term air pollution exposure. Effect modification of the associations between exposure and the mortality outcomes by aMED was examined via interaction terms. RESULTS:, we found significant associations with CVD (HR=1.06; 95% CI: 1.04-1.08), and IHD (HR=1.08; 95% CI: 1.05-1.11). Analyses indicated that Mediterranean diet modified these relationships, as those with a higher aMED score had significantly lower rates of air pollution related mortality ( p interaction<0.05). CONCLUSIONS:Mediterranean diet reduced cardiovascular disease mortality risk related to longterm exposure to air pollutants in a large prospective U.S cohort. Increased consumption of foods rich in antioxidant compounds may aid in reducing the considerable disease burden associated with ambient air pollution.
PMID: 30700142
ISSN: 1524-4539
CID: 3626772
The microbiome in lung cancer tissue and recurrence-free survival
BACKGROUND:Human microbiota have many functions that could contribute to cancer initiation and/or progression at local sites, yet the relation of the lung microbiota to lung cancer prognosis has not been studied. METHODS:In a pilot study, 16S rRNA gene sequencing was performed on paired lung tumor and remote normal samples from the same lobe/segment in 19 non-small cell lung cancer patients. We explored associations of tumor or normal tissue microbiome diversity and composition with recurrence-free and disease-free survival, and compared microbiome diversity and composition between paired tumor and normal samples. RESULTS:Higher richness and diversity in normal tissue were associated with reduced recurrence-free survival (richness p=0.08, Shannon index p=0.03) and disease-free survival (richness p=0.03, Shannon index p=0.02), as was normal tissue overall microbiome composition (Bray-Curtis p=0.09 for recurrence-free and p=0.02 for disease-free survival). In normal tissue, greater abundance of family Koribacteraceae was associated with increased recurrence-free and disease-free survival, while greater abundance of families Bacteroidaceae, Lachnospiraceae, and Ruminococcaceae were associated with reduced recurrence-free or disease-free survival (p<0.05). Tumor tissue diversity and overall composition were not associated with recurrence-free or disease-free survival. Tumor tissue had lower richness and diversity (p≤0.0001) than paired normal tissue, though overall microbiome composition did not differ between paired samples. CONCLUSIONS:We demonstrate, for the first time, a potential relationship between the normal lung microbiota and lung cancer prognosis, which requires confirmation in a larger study. IMPACT/CONCLUSIONS:Definition of bacterial biomarkers of prognosis may lead to improved survival outcomes for lung cancer patients.
PMID: 30733306
ISSN: 1538-7755
CID: 3632422
Novel Common Genetic Susceptibility Loci for Colorectal Cancer
Background/UNASSIGNED:Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. Methods/UNASSIGNED:We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. Results/UNASSIGNED:The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. Conclusions/UNASSIGNED:This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
PMID: 29917119
ISSN: 1460-2105
CID: 3157862
Prior antibiotic exposure and risk of type 2 diabetes among Veterans
BACKGROUND:Exposure to antibiotics may increase the risk of type 2 diabetes. Veterans are at increased risk for diabetes and for exposure to antibiotics. OBJECTIVE:To determine the impact of antibiotic exposure for risk of diabetes. DESIGN/METHODS:Retrospective cohort study. PARTICIPANTS/METHODS:Veterans at the New York Harbor Healthcare System enrolled in primary care, 2004-2014, with ≥2 glycosylated hemoglobin test results <6.5%. MAIN MEASURES/METHODS:The primary exposure was any antimicrobial prescribed >6 months prior to the date of diabetes diagnosis, loss to follow-up, death, or the end of the study, measured as the number of courses of antimicrobial prescriptions filled and the mean daily dose (MDD). The primary outcome was incident diagnosis of diabetes through 2014, defined ≥2 ICD-9 codes for diabetes or ≥2 prescriptions of diabetes medications, other than metformin. Cox proportional hazards regression was used to model antimicrobial medications, demographic and anthropometric measures, and comorbid cardiovascular conditions to incident diabetes. Models incorporated time varying covariates of antimicrobial medication and MDD to analyze associations by antimicrobial class. KEY RESULTS/RESULTS:Among 14,361 Veterans, 9922 (69.1%) were prescribed any antimicrobial medication during the study period. 1413 (9.8%) individuals developed type 2 diabetes. Increased risk of diabetes was associated with >1 prescription (HR 1.13 [1.01-1.26]) compared to none. Time varying analysis of the total number of cumulative courses prescribed showed increased diabetes risk for cephalosporin (HR 1.17 [1.04-1.31]), macrolide (HR 1.08 [1.03-1.13]) and penicillin (HR 1.05 [1.02-1.07]). MDD showed increased risk per 100-unit (mg) increase in antibiotic exposure from (HR 1.05 [1.02-1.08]) for sulfonamide to (HR 1.70 [1.51-1.92]) for cephalosporin. CONCLUSION/CONCLUSIONS:Any and repeated exposure to certain antibiotics may increase diabetes risk among Veterans. Results from this study add to the growing evidence suggesting that antibiotic exposure increases risk for diabetes. Antibiotic stewardship may be enhanced by better understanding this risk, and may lower the incidence of diabetes in populations at risk.
PMID: 30025678
ISSN: 1878-0210
CID: 3202242
Discovery of common and rare genetic risk variants for colorectal cancer
To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
PMID: 30510241
ISSN: 1546-1718
CID: 3520602
Combined effect of modifiable and non-modifiable risk factors for colorectal cancer risk in a pooled analysis of 11 population-based studies
Objective/UNASSIGNED:'Environmental' factors associated with colorectal cancer (CRC) risk include modifiable and non-modifiable variables. Whether those with different non-modifiable baseline risks will benefit similarly from reducing their modifiable CRC risks remains unclear. Design/UNASSIGNED:Using 7945 cases and 8893 controls from 11 population-based studies, we combined 17 risk factors to characterise the overall environmental predisposition to CRC (environmental risk score (E-score)). We estimated the absolute risks (ARs) of CRC of 10 and 30 years across E-score using incidence-rate data from the Surveillance, Epidemiology, and End Results programme. We then combined the modifiable risk factors and estimated ARs across the modifiable risk score, stratified by non-modifiable risk profile based on genetic predisposition, family history and height. Results/UNASSIGNED:, 1.33; 95% CI 1.30 to 1.37). Across E-scores, 30-year ARs of CRC increased from 2.5% in the lowest quartile (Q1) to 5.9% in the highest (Q4) quartile for men, and from 2.1% to 4.5% for women. The modifiable risk score had a stronger association in those with high non-modifiable risk (relative excess risk due to interaction=1.2, 95% CI 0.5 to 1.9). For those in Q4 of non-modifiable risk, a decrease in modifiable risk reduced 30-year ARs from 8.9% to 3.4% for men and from 6.0% to 3.2% for women, a level lower or comparable to the average population risk. Conclusions/UNASSIGNED:Changes in modifiable risk factors may result in a substantial decline in CRC risk in both sexes. Those with high inherited risk may reap greater benefit from lifestyle modifications. Our results suggested comprehensive evaluation of environmental factors may facilitate CRC risk stratification.
PMCID:6904202
PMID: 31875139
ISSN: 2054-4774
CID: 4244232
Association of dietary fibre intake and gut microbiota in adults
Increasing evidence indicates that gut microbiota may influence colorectal cancer risk. Diet, particularly fibre intake, may modify gut microbiota composition, which may affect cancer risk. We investigated the relationship between dietary fibre intake and gut microbiota in adults. Using 16S rRNA gene sequencing, we assessed gut microbiota in faecal samples from 151 adults in two independent study populations: National Cancer Institute (NCI), n 75, and New York University (NYU), n 76. We calculated energy-adjusted fibre intake based on FFQ. For each study population with adjustment for age, sex, race, BMI and smoking, we evaluated the relationship between fibre intake and gut microbiota community composition and taxon abundance. Total fibre intake was significantly associated with overall microbial community composition in NYU (P=0·008) but not in NCI (P=0·81). In a meta-analysis of both study populations, higher fibre intake tended to be associated with genera of class Clostridia, including higher abundance of SMB53 (fold change (FC)=1·04, P=0·04), Lachnospira (FC=1·03, P=0·05) and Faecalibacterium (FC=1·03, P=0·06), and lower abundance of Actinomyces (FC=0·95, P=0·002), Odoribacter (FC=0·95, P=0·03) and Oscillospira (FC=0·96, P=0·06). A species-level meta-analysis showed that higher fibre intake was marginally associated with greater abundance of Faecalibacterium prausnitzii (FC=1·03, P=0·07) and lower abundance of Eubacterium dolichum (FC=0·96, P=0·04) and Bacteroides uniformis (FC=0·97, P=0·05). Thus, dietary fibre intake may impact gut microbiota composition, particularly class Clostridia, and may favour putatively beneficial bacteria such as F. prausnitzii. These findings warrant further understanding of diet-microbiota relationships for future development of colorectal cancer prevention strategies.
PMID: 30355393
ISSN: 1475-2662
CID: 3384862
Cancer epidemiology biomarkers & prevention. 2018:27(10):1168-1175.DOI: 10.1158/1055-9965.EPI-18-0287
Oral Alpha, Beta and Gamma HPV Types and Risk of Incident Esophageal Cancer
BACKGROUND:Several studies have examined association between human papillomaviruses (HPVs) and esophageal cancer, but results have been inconsistent. This is the first prospective study to investigate associations between alpha, beta and gamma HPV detection in the oral cavity and risk of esophageal cancer. METHODS:We conducted a nested case-control study among 96,650 cancer-free participants in the American Cancer Society Cancer Prevention Cohort and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Incident esophageal cancer cases (n=125) were identified during an average 3.9 years of follow-up. Three controls per case (n=372) were selected and matched on age, sex, race/ethnicity and time since mouthwash collection. Alpha, beta and gamma HPV DNA in oral samples was detected using a next-generation sequencing assay. Conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI), adjusting for smoking and alcohol consumption. Statistical significance was evaluated using permutation test. RESULTS:Prevalence of oral alpha, beta, and gamma HPV was 18.4%, 64.8%, and 42.4% in cases and 14.3%, 55.1%, and 33.6% in controls, respectively. Oral HPV16 detection was not associated with esophageal cancer (OR=0.54, 95%CI 0.1-4.84) and none of the esophageal squamous cell carcinoma cases (n=28) were HPV16 positive. Some oral HPV types were more common in cases than controls; however, none of the associations were statistically significant. CONCLUSION/CONCLUSIONS:Although HPVs in oral cavity are very common, this study showed no evidence of association between oral HPVs and esophageal cancer. IMPACT/CONCLUSIONS:Oral HPVs may not contribute to risk of esophageal cancer.
PMID: 30087123
ISSN: 1538-7755
CID: 3226592
Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2018:115(38):9592-9597.DOI: 10.1073/pnas.1803222115
Global estimates of mortality associated with long-term exposure to outdoor fine particulate matter
Exposure to ambient fine particulate matter (PM2.5) is a major global health concern. Quantitative estimates of attributable mortality are based on disease-specific hazard ratio models that incorporate risk information from multiple PM2.5 sources (outdoor and indoor air pollution from use of solid fuels and secondhand and active smoking), requiring assumptions about equivalent exposure and toxicity. We relax these contentious assumptions by constructing a PM2.5-mortality hazard ratio function based only on cohort studies of outdoor air pollution that covers the global exposure range. We modeled the shape of the association between PM2.5 and nonaccidental mortality using data from 41 cohorts from 16 countries-the Global Exposure Mortality Model (GEMM). We then constructed GEMMs for five specific causes of death examined by the global burden of disease (GBD). The GEMM predicts 8.9 million [95% confidence interval (CI): 7.5-10.3] deaths in 2015, a figure 30% larger than that predicted by the sum of deaths among the five specific causes (6.9; 95% CI: 4.9-8.5) and 120% larger than the risk function used in the GBD (4.0; 95% CI: 3.3-4.8). Differences between the GEMM and GBD risk functions are larger for a 20% reduction in concentrations, with the GEMM predicting 220% higher excess deaths. These results suggest that PM2.5 exposure may be related to additional causes of death than the five considered by the GBD and that incorporation of risk information from other, nonoutdoor, particle sources leads to underestimation of disease burden, especially at higher concentrations.
PMID: 30181279
ISSN: 1091-6490
CID: 3271242
Association between long-term exposure to ambient air pollution and diabetes mortality in the US
OBJECTIVE:Recent mechanistic and epidemiological evidence implicates air pollution as a potential risk factor for diabetes; however, mortality risks have not been evaluated in a large US cohort assessing exposures to multiple pollutants with detailed consideration of personal risk factors for diabetes. RESEARCH DESIGN AND METHODS/METHODS:. Associations between the air pollutants and the risk of diabetes mortality (N = 3598) were evaluated using multivariate Cox proportional hazards models adjusted for both individual-level and census-level contextual covariates. RESULTS:(HR = 1.09; 95% CI: 1.01-1.18 per 10 ppb). The strength of the relationship was robust to alternate exposure assessments and model specifications. We also observed significant effect modification, with elevated mortality risks observed among those with higher BMI and lower levels of fruit consumption. CONCLUSIONS:, is related to increased risk of diabetes mortality in the U.S, with attenuation of adverse effects by lower BMI and higher fruit consumption, suggesting that air pollution is involved in the etiology and/or control of diabetes.
PMCID:5999582
PMID: 29778967
ISSN: 1096-0953
CID: 3129652
