Faculty Bibliography
Searched for:
person:hayesr03
Total Results:
528
Bacteroides vulgatus and Bacteroides dorei predict immune-related adverse events in immune checkpoint blockade treatment of metastatic melanoma
BACKGROUND:Immune checkpoint blockade (ICB) shows lasting benefits in advanced melanoma; however, not all patients respond to this treatment and many develop potentially life-threatening immune-related adverse events (irAEs). Identifying individuals who will develop irAEs is critical in order to improve the quality of care. Here, we prospectively demonstrate that the gut microbiome predicts irAEs in melanoma patients undergoing ICB. METHODS:Pre-, during, and post-treatment stool samples were collected from 27 patients with advanced stage melanoma treated with IPI (anti-CTLA-4) and NIVO (anti-PD1) ICB inhibitors at NYU Langone Health. We completed 16S rRNA gene amplicon sequencing, DNA deep shotgun metagenomic, and RNA-seq metatranscriptomic sequencing. The divisive amplicon denoising algorithm (DADA2) was used to process 16S data. Taxonomy for shotgun sequencing data was assigned using MetaPhlAn2, and gene pathways were assigned using HUMAnN 2.0. Compositionally aware differential expression analysis was performed using ANCOM. The Cox-proportional hazard model was used to assess the prospective role of the gut microbiome (GMB) in irAES, with adjustment for age, sex, BMI, immune ICB treatment type, and sequencing batch. RESULTS:= 0.88, p < 0.001). CONCLUSIONS:We identified two distinct fecal bacterial community clusters which are associated differentially with irAEs in ICB-treated advanced melanoma patients.
PMCID:8513370
PMID: 34641962
ISSN: 1756-994x
CID: 5046112
Smoking Behavior and Prognosis After Colorectal Cancer Diagnosis: A Pooled Analysis of 11 Studies
Background/UNASSIGNED:Smoking has been associated with colorectal cancer (CRC) incidence and mortality in previous studies, but current evidence on smoking in association with survival after CRC diagnosis is limited. Methods/UNASSIGNED:We pooled data from 12 345 patients with stage I-IV CRC from 11 epidemiologic studies in the International Survival Analysis in Colorectal Cancer Consortium. Cox proportional hazards regression models were used to evaluate the associations of prediagnostic smoking behavior with overall, CRC-specific, and non-CRC-specific survival. Results/UNASSIGNED:Among 12 345 patients with CRC, 4379 (35.5%) died (2515 from CRC) over a median follow-up time of 7.5 years. Smoking was strongly associated with worse survival in stage I-III patients, whereas no association was observed among stage IV patients. Among stage I-III patients, clear dose-response relationships with all survival outcomes were seen for current smokers. For example, current smokers with 40 or more pack-years had statistically significantly worse overall, CRC-specific, and non-CRC-specific survival compared with never smokers (hazard ratio [HR] =1.94, 95% confidence interval [CI] =1.68 to 2.25; HR = 1.41, 95% CI = 1.12 to 1.78; and HR = 2.67, 95% CI = 2.19 to 3.26, respectively). Similar associations with all survival outcomes were observed for former smokers who had quit for less than 10 years, but only a weak association with non-CRC-specific survival was seen among former smokers who had quit for more than 10 years. Conclusions/UNASSIGNED:This large consortium of CRC patient studies provides compelling evidence that smoking is strongly associated with worse survival of stage I-III CRC patients in a clear dose-response manner. The detrimental effect of smoking was primarily related to noncolorectal cancer events, but current heavy smoking also showed an association with CRC-specific survival.
PMCID:8561259
PMID: 34738070
ISSN: 2515-5091
CID: 5038442
Cancer epidemiology biomarkers & prevention. 2021:30(10):1775-1777.DOI: 10.1158/1055-9965.EPI-21-0844
Advances in Understanding Early-Onset Colorectal Cancer [Comment]
Since the 1990s, the incidence of early-onset colorectal cancer (at <50 years of age) in the US has increased by more than 50%; similar increases have also been observed internationally. These increases are found particularly among individuals born during and after the 1960s, raising the possibility that the increased rates of early-onset colorectal cancer are attributable to changes in risk-factor patterns throughout successive generations. The reasons for these alarming epidemiologic patterns for early-onset colorectal cancer worldwide are only recently being investigated and major gaps in our knowledge remain. In the current issue of this journal, Arif and colleagues differentiated characteristics and outcomes of early-onset colorectal cancer in patients with the predisposing conditions of inflammatory bowel disease or hereditary genetic syndromes, compared with patients who have sporadic disease. Also, in this issue, Schumacher and colleagues investigated risk factors for early-onset colorectal adenocarcinoma in a nested case-control study among Kaiser Permanente Southern California (KPSC) health plan members. The research presented on characteristics and outcomes points to the importance of sporadic disease in the rise of early-onset colorectal cancer, while the research presented on risk factors points to the importance of obesity as a potential explanatory factor for this rise.See related articles by Arif et al., p. 1785 and by Schumacher et al., p. 1792.
PMID: 34607882
ISSN: 1538-7755
CID: 5061822
Cancer epidemiology biomarkers & prevention. 2021:30(7):1328-1335.DOI: 10.1158/1055-9965.EPI-20-1417
Tobacco smoking and the fecal microbiome in a large, multi-ethnic cohort
BACKGROUND:Increasing evidence suggests that tobacco smoking, a well-known driver of carcinogenesis, influences the gut microbiome; however, these relationships remain understudied in diverse populations. Thus, we performed an analysis of smoking and the gut microbiome in a subset of 803 adults from the multi-ethnic NYU FAMiLI study. METHODS:We assessed fecal microbiota using 16S rRNA gene sequencing, and clustered samples into Amplicon Sequence Variants using QIIME2. We evaluated inferred microbial pathway abundance using PICRUSt. We compared population beta diversity, and relative taxonomic and functional pathway abundance, between never smokers, former smokers, and current smokers. RESULTS:We found that the overall composition of the fecal microbiome in former and current smokers differs significantly from that of never smokers. The taxa Prevotella and Veillonellaceae were enriched in current and former smokers, while the taxa Lachnospira and Tenericutes were depleted, relative to never smokers. These shifts were consistent across racial and ethnic subgroups. Relative to never smokers, the abundance of taxa enriched in current smokers were positively correlated with the imputed abundance of pathways involving smoking-associated toxin breakdown and response to reactive oxygen species (ROS). CONCLUSIONS:Our findings suggest common mechanisms of smoking associated microbial change across racial subgroups, regardless of initial microbiome composition. The correlation of these differentials with ROS exposure pathways may suggest a role for these taxa in the known association between smoking, ROS and carcinogenesis. IMPACT/CONCLUSIONS:Smoking shifts in the microbiome may be independent of initial composition, stimulating further studies on the microbiome in carcinogenesis and cancer prevention.
PMID: 34020999
ISSN: 1538-7755
CID: 4888752
Genetic architectures of proximal and distal colorectal cancer are partly distinct
OBJECTIVE:An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined. DESIGN/METHODS:To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling. RESULTS:) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer. CONCLUSION/CONCLUSIONS:Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
PMID: 33632709
ISSN: 1468-3288
CID: 4794922
Nongenetic Determinants of Risk for Early-Onset Colorectal Cancer
Background/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED: = .04). Conclusion/UNASSIGNED: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.
PMCID:8134523
PMID: 34041438
ISSN: 2515-5091
CID: 4888152
Environmental Influences on the Human Microbiome and Implications for Noncommunicable Disease
The human microbiome contributes metabolic functions, protects against pathogens, educates the immune system, and through these basic functions, directly or indirectly, affects most of our physiologic functions. Here, we consider the human microbiome and its relationship to several major noncommunicable human conditions, including orodigestive tract cancers, neurologic diseases, diabetes, and obesity. We also highlight the scope of contextual macroenvironmental factors (toxicological and chemical environment, built environment, and socioeconomic environment) and individual microenvironmental factors (smoking, alcohol, and diet) that may push the microbiota toward less healthy or more healthy conditions, influencing the development of these diseases. Last, we highlight current uncertainties and challenges in the study of environmental influences on the human microbiome and implications for understanding noncommunicable disease, suggesting a research agenda to strengthen the scientific evidence base.
PMID: 33798404
ISSN: 1545-2093
CID: 4862382
Assessment of a Polygenic Risk Score for Colorectal Cancer to Predict Risk of Lynch Syndrome Colorectal Cancer
It was not known whether the polygenic risk scores (PRSs) that predict colorectal cancer could predict colorectal cancer for people with inherited pathogenic variants in DNA mismatch repair genes-people with Lynch syndrome. We tested a PRS comprising 107 established single-nucleotide polymorphisms associated with colorectal cancer in European populations for 826 European-descent carriers of pathogenic variants in DNA mismatch repair genes (293 MLH1, 314 MSH2, 126 MSH6, 71 PMS2, and 22 EPCAM) from the Colon Cancer Family Registry, of whom 504 had colorectal cancer. There was no evidence of an association between the PRS and colorectal cancer risk, irrespective of which DNA mismatch repair gene was mutated, or sex (all 2-sided P > .05). The hazard ratio per standard deviation of the PRS for colorectal cancer was 0.97 (95% confidence interval = 0.88 to 1.06; 2-sided P = .51). Whereas PRSs are predictive of colorectal cancer in the general population, they do not predict Lynch syndrome colorectal cancer.
PMCID:8062848
PMID: 33928216
ISSN: 2515-5091
CID: 5017902
Evaluation of a commercial database to estimate residence histories in the Los Angeles Ultrafines Study
BACKGROUND:Commercial databases can be used to identify participant addresses over time, but their quality and impact on environmental exposure assessment is uncertain. OBJECTIVE:To evaluate the performance of a commercial database to find residences and estimate environmental exposures for study participants. METHODS:We searched LexisNexis® for participant addresses in the Los Angeles Ultrafines Study, a prospective cohort of men and women aged 50-71 years. At enrollment (1995-1996) and follow-up (2004-2005), we evaluated attainment (address found for the corresponding time period) and match rates to survey addresses by participant characteristics. We compared geographically-referenced predictors and estimates of ultrafine particulate matter (UFP) exposure from a land use regression model using LexisNexis and survey addresses at enrollment. RESULTS:LexisNexis identified an address for 69% of participants at enrollment (N=50,320) and 95% of participants at follow-up (N=24,432). Attainment rate at enrollment modestly differed (≥5%) by age, smoking status, education, and residential mobility between surveys. The match rate at both survey periods was high (82-86%) and similar across characteristics. When using LexisNexis versus survey addresses, correlations were high for continuous values of UFP exposure and its predictors (rho=0.86-0.92). SIGNIFICANCE/CONCLUSIONS:Time period and population characteristics influenced the attainment of addresses from a commercial database, but accuracy and subsequent estimation of specific air pollution exposures were high in our older study population.
PMID: 33689822
ISSN: 1096-0953
CID: 4809332
Response to Li and Hopper [Comment]
PMID: 33667396
ISSN: 1537-6605
CID: 4835862
