Faculty Bibliography
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543
Global patterns and trends in colorectal cancer incidence in young adults
OBJECTIVE:Early-onset colorectal cancer (CRC) is increasing in the USA despite rapid declines in older ages. Similar patterns are reported in Australia and Canada, but a comprehensive global analysis of contemporary data is lacking. DESIGN/METHODS:We extracted long-term data from Cancer Incidence in Five Continents and supplemental sources to report on worldwide CRC incidence rates and trends by age (20-49 years and ≥50 years) through diagnosis year 2012 or beyond (Australia, Finland, New Zealand, Norway, Sweden, USA). RESULTS:During 2008-2012, age-standardised CRC incidence rates in adults <50 ranged from 3.5 per 100 000 (95% CI 3.2 to 3.9) in India (Chennai) to 12.9 (95% CI 12.6 to 13.3) in Korea. During the most recent decade of available data, incidence in adults <50 was stable in 14 of 36 countries; declined in Austria, Italy and Lithuania; and increased in 19 countries, nine of which had stable or declining trends in older adults (Australia, Canada, Denmark, Germany, New Zealand, Slovenia, Sweden, UK and USA). In Cyprus, Netherlands and Norway, inclines in incidence in young adults were twice as rapid as those in older adults (eg, Norway average annual per cent change (AAPC), 1.9 (95% CI 1.4 to 2.5) vs 0.5 (95% CI 0.3 to 0.7)). Among most high-income countries with long-term data, the uptick in early-onset disease began in the mid-1990s. The steepest increases in young adults were in Korea (AAPC, 4.2 (95% CI 3.4 to 5.0)) and New Zealand (AAPC, 4.0 (95% CI 2.1 to 6.0)). CONCLUSION/CONCLUSIONS:CRC incidence increased exclusively in young adults in nine high-income countries spanning three continents, potentially signalling changes in early-life exposures that influence large bowel carcinogenesis.
PMID: 31488504
ISSN: 1468-3288
CID: 4069162
A Summary of the Fight Colorectal Cancer Working Meeting: Exploring Risk Factors and Etiology of Sporadic Early-Age Onset Colorectal Cancer
PMID: 31095950
ISSN: 1528-0012
CID: 4028662
Association Between Intake of Red and Processed Meat and Survival in Patients With Colorectal Cancer in a Pooled Analysis
BACKGROUND & AIMS/OBJECTIVE:Red and processed meat intake is associated with colorectal cancer (CRC) incidence, but it is not clear if intake is associated with patient survival after diagnosis. METHODS:We pooled data from 7627 patients with stage I-IV CRC from 10 studies in the International Survival Analysis in Colorectal Cancer Consortium. Cox proportional hazards regression models were used to evaluate the associations of intake of red and processed meat before diagnosis with overall and CRC-specific survival. RESULTS:Among 7627 patients with CRC, 2338 died, including 1576 from CRC, over a median follow-up time of 5.1 years. In multivariable-adjusted analyses, higher intake of red or processed meat was not associated with overall survival of patients with stage I-III CRC: Q4 vs Q1 red meat hazard ratio [HR], 1.08 (95% CI, 0.93-1.26) and Q4 vs Q1 processed meat HR, 1.10 (95% CI, 0.93-1.32) or with CRC-specific survival: Q4 vs Q1 red meat HR, 1.09 (95% CI, 0.89-1.33) and Q4 vs Q1 processed meat HR, 1.11 (95% CI, 0.87-1.42). Results were similar for patients with stage IV CRC. However, patients with stage I-III CRC who reported an intake of processed meat above the study-specific medians had a higher risk of death from any cause (HR, 1.12; 95% CI, 1.01-1.25) than patients who reported eating at or less than the median. CONCLUSION/CONCLUSIONS:In this large consortium of CRC patient cohorts, intake of red and processed meat before a diagnosis of CRC was not associated with shorter survival time after diagnosis, although a possible weak adverse association cannot be excluded. Studies that evaluate dietary data from several time points before and after cancer diagnosis are required to confirm these findings.
PMCID:6533164
PMID: 30476588
ISSN: 1542-7714
CID: 3999882
Incense Burning is Associated with Human Oral Microbiota Composition
Incense burning is common worldwide and produces environmental toxicants that may influence health; however, biologic effects have been little studied. In 303 Emirati adults, we tested the hypothesis that incense use is linked to compositional changes in the oral microbiota that can be potentially significant for health. The oral microbiota was assessed by amplification of the bacterial 16S rRNA gene from mouthwash samples. Frequency of incense use was ascertained through a questionnaire and examined in relation to overall oral microbiota composition (PERMANOVA analysis), and to specific taxon abundances, by negative binomial generalized linear models. We found that exposure to incense burning was associated with higher microbial diversity (p < 0.013) and overall microbial compositional changes (PERMANOVA, p = 0.003). Our study also revealed that incense use was associated with significant changes in bacterial abundances (i.e. depletion of the dominant taxon Streptococcus), even in occasional users (once/week or less) implying that incense use impacts the oral microbiota even at low exposure levels. In summary, this first study suggests that incense burning alters the oral microbiota, potentially serving as an early biomarker of incense-related toxicities and related health consequences. Although a common indoor air pollutant, guidelines for control of incense use have yet to be developed.
PMID: 31296925
ISSN: 2045-2322
CID: 3976832
Joint effects of intensity and duration of cigarette smoking on the risk of head and neck cancer: A bivariate spline model approach
OBJECTIVES/OBJECTIVE:This study aimed at re-evaluating the strength and shape of the dose-response relationship between the combined (or joint) effect of intensity and duration of cigarette smoking and the risk of head and neck cancer (HNC). We explored this issue considering bivariate spline models, where smoking intensity and duration were treated as interacting continuous exposures. MATERIALS AND METHODS/METHODS:We pooled individual-level data from 33 case-control studies (18,260 HNC cases and 29,844 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. In bivariate regression spline models, exposures to cigarette smoking intensity and duration (compared with never smokers) were modeled as a linear piecewise function within a logistic regression also including potential confounders. We jointly estimated the optimal knot locations and regression parameters within the Bayesian framework. RESULTS:For oral-cavity/pharyngeal (OCP) cancers, an odds ratio (OR) >5 was reached after 30 years in current smokers of ∼20 or more cigarettes/day. Patterns of OCP cancer risk in current smokers differed across strata of alcohol intensity. For laryngeal cancer, ORs >20 were found for current smokers of ≥20 cigarettes/day for ≥30  years. In former smokers who quit ≥10  years ago, the ORs were approximately halved for OCP cancers, and ∼1/3 for laryngeal cancer, as compared to the same levels of intensity and duration in current smokers. CONCLUSION/CONCLUSIONS:Referring to bivariate spline models, this study better quantified the joint effect of intensity and duration of cigarette smoking on HNC risk, further stressing the need of smoking cessation policies.
PMID: 31178212
ISSN: 1879-0593
CID: 3929662
American journal of respiratory & critical care medicine. 2019:200(8):1022-1031.DOI: 10.1164/rccm.201806-1161OC
Long-term Exposure to Ozone and Cause-Specific Mortality Risk in the U.S
RATIONALE/BACKGROUND:Many studies have linked short-term exposure to ozone (O3) with morbidity and mortality, but epidemiological evidence of associations between long-term ozone exposure and mortality is more limited. OBJECTIVES/OBJECTIVE:We investigated associations of long-term (annual or warm season average) O3 exposure with all-cause and cause-specific mortality in the NIH-AARP Diet and Health Study, a large prospective cohort of U.S. adults with 17 years of follow-up from 1995 to 2011. METHODS:The cohort (N=548,780) was linked to census tract-level estimates for O3. Associations between long-term O3 exposure (averaged values from 2002-2010) and multiple causes of death were evaluated using multivariate Cox proportional hazards models, adjusted for both individual- and census tract-level covariates, as well as potentially confounding co-pollutants and temperature. MEASUREMENTS AND MAIN RESULTS/RESULTS:Long-term annual average exposure to O3 was significantly associated with deaths due to cardiovascular disease (per 10 ppb, HR=1.03; 95% CI: 1.01-1.06), ischemic heart disease (HR=1.06; 95% CI: 1.02-1.09), respiratory disease (HR=1.04; 95% CI: 1.00-1.09), and chronic obstructive pulmonary disease (HR=1.09; 95% CI: 1.03-1.15) in single-pollutant models. The results were robust to alternative models and adjustment for co-pollutants (fine particulate matter and nitrogen dioxide), although some evidence of confounding by temperature was observed. Significantly elevated respiratory disease mortality risk associated with long-term O3 exposure was found among those living in locations with high temperature (p-interaction<0.05). CONCLUSIONS:This study found that long-term exposure to O3 is associated with increased risk for multiple causes of mortality, suggesting that establishment of annual and/or seasonal federal O3 standard(s) are needed to more adequately protect public health from ambient O3 exposures.
PMID: 31051079
ISSN: 1535-4970
CID: 3908832
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
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
Benzene Exposure Response and Risk of Myeloid Neoplasms in Chinese Workers: A Multicenter Case-Cohort Study
Background/UNASSIGNED:There is international consensus that benzene exposure is causally related to acute myeloid leukemia (AML), and more recent evidence of association with myelodysplastic syndromes (MDS). However, there are uncertainties about the exposure response, particularly risks by time since exposure and age at exposure. Methods/UNASSIGNED:In a case-cohort study in 110 631 Chinese workers followed up during 1972-1999 we evaluated combined MDS/AML (n = 44) and chronic myeloid leukemia (n = 18). We estimated benzene exposures using hierarchical modeling of occupational factors calibrated with historical routine measurements, and evaluated exposure response for cumulative exposure and average intensity using Cox regression; P values were two-sided. Results/UNASSIGNED:Increased MDS/AML risk with increasing cumulative exposure in our a priori defined time window (2 to <10 years) before the time at risk was suggested (Ptrend = 08). For first exposure (within the 2 to <10-year window) before age 30 years, the exposure response was stronger (P = .004) with rate ratios of 1.12 (95% confidence interval [CI] = 0.27 to 4.29), 5.58 (95% CI = 1.65 to 19.68), and 4.50 (95% CI = 1.22 to 16.68) for cumulative exposures of more than 0 to less than 40, 40 to less than 100, and at least 100 ppm-years, respectively, compared with no exposure. There was little evidence of exposure response after at least 10 years (Ptrend = .94), regardless of age at first exposure. Average intensity results were generally similar. The risk for chronic myeloid leukemia was increased in exposed vs unexposed workers, but appeared to increase and then decrease with increasing exposure. Conclusion/UNASSIGNED:For myeloid neoplasms, the strongest effects were apparent for MDS/AML arising within 10 years of benzene exposure and for first exposure in the 2 to less than 10-year window before age 30 years.
PMID: 30520970
ISSN: 1460-2105
CID: 3520762
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
