Publications by authors named "Bu-Tian Ji"

145 Publications

Commute patterns, residential traffic-related air pollution, and lung cancer risk in the prospective UK Biobank cohort study.

Environ Int 2021 Oct 15;155:106698. Epub 2021 Jun 15.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20850, USA.

Introduction: Commuting exposes millions of people to carcinogens from traffic-related air pollution (TRAP) but is seldomly considered in epidemiologic studies of lung cancer. In the prospective United Kingdom (UK) Biobank cohort study, we investigated associations between commute patterns, residential nitrogen dioxide concentrations (NO; a surrogate for TRAP), and lung cancer risk.

Methods: We analyzed 234,124 employed participants at baseline (2006-2010). There were 493 incident lung cancer cases diagnosed over an average 7-year follow-up. Subjects were cross-classified into exclusive categories of commute mode (automobile, public transportation, walking, cycling, active mixture, and other mixture) and frequency (regular: 1-4, often: ≥5 work-bound trips/week). Annual average residential NO concentrations in 2005-2007 were estimated with land use regression. Multivariable Cox regression was used to estimate associations between commute patterns, NO quartiles, and incident lung cancer. We conducted analyses stratified by NO (>, ≤median = 28.3 µg/m) and potential confounders such as sex and smoking.

Results: Compared to regular automobile use, commuting often by public transportation was associated with increased lung cancer risk (hazard ratio (HR) = 1.58, 95% confidence intervals (CI):1.08-2.33). Additionally, we found a positive exposure-response relationship with residential NO (HR = 1.21, 95 %CI: 0.90-1.62; HR = 1.48, 95 %CI: 1.10-1.99; HR = 1.58, 95 %CI: 1.13-2.23; p-trend = 3.1 × 10). The public transportation association was observed among those with higher NO (p-interaction = 0.02). Other commute categories were not associated with risk.

Conclusions: Commuters residing in high-NO areas who often use public transportation could have elevated lung cancer risk compared to regular automobile users. These results warrant investigations into which component(s) of public transportation contribute to the observed association with increased lung cancer risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2021.106698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292218PMC
October 2021

Elevated Alu retroelement copy number among workers exposed to diesel engine exhaust.

Occup Environ Med 2021 May 26. Epub 2021 May 26.

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.

Background: Millions of workers worldwide are exposed to diesel engine exhaust (DEE), a known genotoxic carcinogen. Alu retroelements are repetitive DNA sequences that can multiply and compromise genomic stability. There is some evidence linking altered Alu repeats to cancer and elevated mortality risks. However, whether Alu repeats are influenced by environmental pollutants is unexplored. In an occupational setting with high DEE exposure levels, we investigated associations with Alu repeat copy number.

Methods: A cross-sectional study of 54 male DEE-exposed workers from an engine testing facility and a comparison group of 55 male unexposed controls was conducted in China. Personal air samples were assessed for elemental carbon, a DEE surrogate, using NIOSH Method 5040. Quantitative PCR (qPCR) was used to measure Alu repeat copy number relative to albumin (Alb) single-gene copy number in leucocyte DNA. The unitless Alu/Alb ratio reflects the average quantity of Alu repeats per cell. Linear regression models adjusted for age and smoking status were used to estimate relations between DEE-exposed workers versus unexposed controls, DEE tertiles (6.1-39.0, 39.1-54.5 and 54.6-107.7 µg/m) and Alu/Alb ratio.

Results: DEE-exposed workers had a higher average Alu/Alb ratio than the unexposed controls (p=0.03). Further, we found a positive exposure-response relationship (p=0.02). The Alu/Alb ratio was highest among workers exposed to the top tertile of DEE versus the unexposed controls (1.12±0.08 SD vs 1.06±0.07 SD, p=0.01).

Conclusion: Our findings suggest that DEE exposure may contribute to genomic instability. Further investigations of environmental pollutants, Alu copy number and carcinogenesis are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/oemed-2021-107462DOI Listing
May 2021

A Prospective Investigation of Circulating Metabolome Identifies Potential Biomarkers for Gastric Cancer Risk.

Cancer Epidemiol Biomarkers Prev 2021 Apr 1. Epub 2021 Apr 1.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee.

Background: Metabolomics is widely used to identify potential novel biomarkers for cancer risk. No investigation, however, has been conducted to prospectively evaluate the role of perturbation of metabolome in gastric cancer development.

Methods: 250 incident cases diagnosed with primary gastric cancer were selected from the Shanghai Women's Health and the Shanghai Men's Health Study, and each was individually matched to one control by incidence density sampling. An untargeted global profiling platform was used to measure approximately 1,000 metabolites in prediagnostic plasma. Conditional logistic regression was utilized to generate ORs and values.

Results: Eighteen metabolites were associated with gastric cancer risk at < 0.01. Among them, 11 metabolites were lysophospholipids or lipids of other classes; for example, 1-(1-enyl-palmitoyl)-GPE (P-16:0) (OR = 1.56; = 1.89 × 10). Levels of methylmalonate, a suggested biomarker of vitamin B12 deficiency, was correlated with increased gastric cancer risk (OR = 1.42; = 0.004). Inverse associations were found for three biomarkers for coffee/tea consumption (3-hydroxypyridine sulfate, quinate and N-(2-furoyl) glycine), although the associations were only significant when comparing cases that were diagnosed within 5 years after the blood collection to matched controls. Most of the identified associations were more profound in women and never smokers than their male or ever smoking counterparts and some with notable significant interactions.

Conclusions: Our study identified multiple potential risk biomarkers for gastric cancer independent of infection and other major risk factors.

Impact: New risk-assessment tools to identify high-risk population could be developed to improve prevention of gastric cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-20-1633DOI Listing
April 2021

Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia.

Environ Int 2021 02 29;147:105975. Epub 2020 Dec 29.

Department of Internal Medicine, Kaohsiung Medical University Hospital, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2020.105975DOI Listing
February 2021

Variation in oral microbiome is associated with future risk of lung cancer among never-smokers.

Thorax 2021 03 14;76(3):256-263. Epub 2020 Dec 14.

National Cancer Institute, Bethesda, Maryland, USA.

Objective: To prospectively investigate whether diversity in oral microbiota is associated with risk of lung cancer among never-smokers.

Design And Setting: A nested case-control study within two prospective cohort studies, the Shanghai Women's Health Study (n=74 941) and the Shanghai Men's Health Study (n=61 480).

Participants: Lifetime never-smokers who had no cancer at baseline. Cases were subjects who were diagnosed with incident lung cancer (n=114) and were matched 1:1 with controls on sex, age (≤2 years), date (≤30 days) and time (morning/afternoon) of sample collection, antibiotic use during the week before sample collection (yes/no) and menopausal status (for women).

Main Outcomes And Measures: Metagenomic shotgun sequencing was used to measure the community structure and abundance of the oral microbiome in pre-diagnostic oral rinse samples of each case and control. Multivariable logistic regression models were used to estimate the association of lung cancer risk with alpha diversity metrics and relative abundance of taxa. The Microbiome Regression-Based Kernel Association Test (MiRKAT) evaluated the association between risk and the microbiome beta diversity.

Results: Subjects with lower microbiota alpha diversity had an increased risk of lung cancer compared with those with higher microbial alpha diversity (Shannon: p=0.05; Simpson: p=0.04; Observed Species: p=0.64). No case-control differences were apparent for beta diversity (p=0.30). After accounting for multiple comparisons, a greater abundance of Spirochaetia (OR 1.00 (reference), OR 0.61 (95% CI 0.32 to 1.18), OR 0.42 (95% CI 0.21 to 0.85)) and Bacteroidetes (OR 1.00 (reference), OR 0.66 (95% CI 0.35 to 1.25), OR 0.31 (95% CI 0.15 to 0.64)) was associated with a decreased risk of lung cancer, while a greater abundance of the Bacilli class (OR 1.00 (reference), OR 1.49 (95% CI 0.73 to 3.08), OR 2.40 (95% CI 1.18 to 4.87)) and Lactobacillales order (OR 1.00 (reference), OR 2.15 (95% CI 1.03 to 4.47), OR 3.26 (95% CI 1.58 to 6.70)) was associated with an increased risk of lung cancer.

Conclusions: Our prospective study of never-smokers suggests that lower alpha diversity was associated with a greater risk of lung cancer and the abundance of certain specific taxa was associated with altered risk, providing further insight into the aetiology of lung cancer in the absence of active tobacco smoking.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/thoraxjnl-2020-215542DOI Listing
March 2021

White Blood Cell Count and Risk of Incident Lung Cancer in the UK Biobank.

JNCI Cancer Spectr 2020 Apr 12;4(2):pkz102. Epub 2019 Dec 12.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.

Background: The contribution of measurable immunological and inflammatory parameters to lung cancer development remains unclear, particularly among never smokers. We investigated the relationship between total and differential white blood cell (WBC) counts and incident lung cancer risk overall and among subgroups defined by smoking status and sex in the United Kingdom (UK).

Methods: We evaluated 424 407 adults aged 37-73 years from the UK Biobank. Questionnaires, physical measurements, and blood were administered and collected at baseline in 2006-2010. Complete blood cell counts were measured using standard methods. Lung cancer diagnoses and histological classifications were obtained from cancer registries. Multivariable Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence intervals of incident lung cancer in relation to quartiles (Q) of total WBC and subtype-specific counts, with Q1 as the reference.

Results: There were 1493 incident cases diagnosed over an average 7-year follow-up. Overall, the highest quartile of total WBC count was statistically significantly associated with elevated lung cancer risk (HR = 1.67, 95% CI = 1.41 to 1.98). Among women, increased risks were found in current smokers ( /  = 244 / 19 464, HR = 2.15, 95% CI = 1.46 to 3.16), former smokers ( /  = 280 / 69 198, HR = 1.75, 95% CI = 1.24 to 2.47), and never smokers without environmental tobacco smoke exposure (n / n = 108 / 111 294, HR = 1.93, 95% CI = 1.11 to 3.35). Among men, stronger associations were identified in current smokers (n /  = 329 / 22 934, HR = 2.95, 95% CI = 2.04 to 4.26) and former smokers ( /  = 358/71 616, HR = 2.38, 95% CI = 1.74 to 3.27) but not in never smokers. Findings were similar for lung adenocarcinoma and squamous cell carcinoma and were driven primarily by elevated neutrophil fractions.

Conclusions: Elevated WBCs could potentially be one of many important markers for increased lung cancer risk, especially among never-smoking women and ever-smoking men.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jncics/pkz102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083262PMC
April 2020

Benzene exposure-response and risk of lymphoid neoplasms in Chinese workers: A multicenter case-cohort study.

Am J Ind Med 2020 09 31;63(9):741-754. Epub 2020 May 31.

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, Maryland.

Background: While international agreement supports a causal relationship of benzene exposure with acute myeloid leukemia, there is debate about benzene and lymphoid neoplasm risks.

Methods: In a case-cohort study with follow-up of 110 631 Chinese workers during 1972-1999, we evaluated benzene exposure-response for non-Hodgkin lymphoma (NHL), lymphoid leukemias (LL), acute lymphocytic leukemia (ALL), and total lymphoid neoplasms (LN). We estimated benzene exposures using state-of-the-art hierarchical modeling of occupational factors calibrated with historical routine measurements and evaluated cumulative exposure-response using Cox regression.

Results: NHL and other specified LN were increased in exposed vs unexposed workers. However, there was no evidence of exposure-response for NHL or other specified LN. Based on a linear exposure-response, relative risks at 100 parts per million-years (RR at 100 ppm-years) for cumulative benzene exposure using a 2-year lag (exposure at least 2 years before the time at risk) were 1.05 for NHL (95 percent confidence interval (CI) = 0.97, 1.27; 32 cases), 1.11 for LL (95% CI < 0, 1.66; 12 cases), 1.21 for ALL (95% CI < 0, 3.53; 10 cases), and 1.02 for total LN (95% CI < 0, 1.16; 49 cases). No statistically significant exposure-response trends were apparent for these LN for 2 to <10-year or ≥10-year lags. NHL risks were not significantly modified by sex, age, or year at first exposure, attained age, or time since exposure.

Conclusion: Given the study strengths and limitations, we found little evidence of exposure-response for benzene and NHL, LL, ALL, or total LN, although NHL and other specified LN were increased in exposed vs unexposed individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajim.23142DOI Listing
September 2020

Association of Untargeted Urinary Metabolomics and Lung Cancer Risk Among Never-Smoking Women in China.

JAMA Netw Open 2019 09 4;2(9):e1911970. Epub 2019 Sep 4.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland.

Importance: Chinese women have the highest rate of lung cancer among female never-smokers in the world, and the etiology is poorly understood.

Objective: To assess the association between metabolomics and lung cancer risk among never-smoking women.

Design, Setting, And Participants: This nested case-control study included 275 never-smoking female patients with lung cancer and 289 never-smoking cancer-free control participants from the prospective Shanghai Women's Health Study recruited from December 28, 1996, to May 23, 2000. Validated food frequency questionnaires were used for the collection of dietary information. Metabolomic analysis was conducted from November 13, 2015, to January 6, 2016. Data analysis was conducted from January 6, 2016, to November 29, 2018.

Exposures: Untargeted ultra-high-performance liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance metabolomic profiles were characterized using prediagnosis urine samples. A total of 39 416 metabolites were measured.

Main Outcomes And Measures: Incident lung cancer.

Results: Among the 564 women, those who developed lung cancer (275 participants; median [interquartile range] age, 61.0 [52-65] years) and those who did not develop lung cancer (289 participants; median [interquartile range] age, 62.0 [53-66] years) at follow-up (median [interquartile range] follow-up, 10.9 [9.0-11.7] years) were similar in terms of their secondhand smoke exposure, history of respiratory diseases, and body mass index. A peak metabolite, identified as 5-methyl-2-furoic acid, was significantly associated with lower lung cancer risk (odds ratio, 0.57 [95% CI, 0.46-0.72]; P < .001; false discovery rate = 0.039). Furthermore, this peak was weakly correlated with self-reported dietary soy intake (ρ = 0.21; P < .001). Increasing tertiles of this metabolite were associated with lower lung cancer risk (in comparison with first tertile, odds ratio for second tertile, 0.52 [95% CI, 0.34-0.80]; and odds ratio for third tertile, 0.46 [95% CI, 0.30-0.70]), and the association was consistent across different histological subtypes and follow-up times. Additionally, metabolic pathway analysis found several systemic biological alterations that were associated with lung cancer risk, including 1-carbon metabolism, nucleotide metabolism, oxidative stress, and inflammation.

Conclusions And Relevance: This prospective study of the untargeted urinary metabolome and lung cancer among never-smoking women in China provides support for the hypothesis that soy-based metabolites are associated with lower lung cancer risk in never-smoking women and suggests that biological processes linked to air pollution may be associated with higher lung cancer risk in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2019.11970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755532PMC
September 2019

Constituents of Household Air Pollution and Risk of Lung Cancer among Never-Smoking Women in Xuanwei and Fuyuan, China.

Environ Health Perspect 2019 09 5;127(9):97001. Epub 2019 Sep 5.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA.

Background: Lung cancer rates among never-smoking women in Xuanwei and Fuyuan in China are among the highest in the world and have been attributed to the domestic use of smoky (bituminous) coal for heating and cooking. However, the key components of coal that drive lung cancer risk have not been identified.

Objectives: We aimed to investigate the relationship between lifelong exposure to the constituents of smoky coal (and other fuel types) and lung cancer.

Methods: Using a population-based case-control study of lung cancer among 1,015 never-smoking female cases and 485 controls, we examined the association between exposure to 43 household air pollutants and lung cancer. Pollutant predictions were derived from a comprehensive exposure assessment study, which included methylated polycyclic aromatic hydrocarbons (PAHs), which have never been directly evaluated in an epidemiological study of any cancer. Hierarchical clustering and penalized regression were applied in order to address high colinearity in exposure variables.

Results: The strongest association with lung cancer was for a cluster of 25 PAHs [odds ratio (OR): 2.21; 95% confidence interval (CI): 1.67, 2.87 per 1 standard deviation (SD) change], within which 5-methylchrysene (5-MC), a mutagenic and carcinogenic PAH, had the highest individual observed OR (5.42; 95% CI: 0.94, 27.5). A positive association with nitrogen dioxide ([Formula: see text]) was also observed (OR: 2.06; 95% CI: 1.19, 3.49). By contrast, neither benzo(a)pyrene (BaP) nor fine particulate matter with aerodynamic diameter [Formula: see text] ([Formula: see text]) were associated with lung cancer in the multipollutant models.

Conclusions: To our knowledge, this is the first study to comprehensively evaluate the association between lung cancer and household air pollution (HAP) constituents estimated over the entire life course. Given the global ubiquity of coal use domestically for indoor cooking and heating and commercially for electric power generation, our study suggests that more extensive monitoring of coal combustion products, including methylated PAHs, may be warranted to more accurately assess health risks and develop prevention strategies from this exposure. https://doi.org/10.1289/EHP4913.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1289/EHP4913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792381PMC
September 2019

Ischaemic heart disease and stroke mortality by specific coal type among non-smoking women with substantial indoor air pollution exposure in China.

Int J Epidemiol 2020 02;49(1):56-68

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.

Background: Lifetime use of bituminous ('smoky') coal is associated with nearly a 100-fold higher risk of lung cancer mortality compared with anthracite ('smokeless') coal use in rural Xuanwei, China, among women. Risk of mortality from ischaemic heart disease (IHD) and stroke for these coal types has not been evaluated.

Methods: A cohort of 16 323 non-smoking women in Xuanwei, who were lifetime users of either smoky or smokeless coal, were followed up from 1976 to 2011. We estimated hazard ratios (HRs) and 95% confidence intervals (CI) to evaluate lifetime use of coal types and stoves in the home in relation to risk of IHD and stroke mortality.

Results: Among lifetime users of smokeless coal, higher average exposure intensity (≥4 tons/year vs <2.5 tons/year, HR = 7.9, 95% CI = 3.5-17.8; Ptrend =<0.0001) and cumulative exposure (>64 ton-years vs ≤28 ton-years, HR = 6.5, 95% CI = 1.5-28.3; Ptrend =0.003) during follow-up and over their lifetime was associated with increased IHD mortality, and ventilated stove use dramatically reduced this risk (HR = 0.2, 95% CI 0.1-0.5). Higher cumulative exposure to smoky coal during follow-up showed positive associations with IHD mortality, but the evidence for other metrics was less consistent compared with associations with smokeless coal use.

Conclusions: Higher use of smokeless coal, which is burned throughout China and is generally regarded to be a cleaner fuel type, is associated with IHD mortality. Use of cleaner fuels or stove interventions may be effective in reducing the increasing burden of IHD in developing regions that currently rely on smokeless coal for cooking and heating.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ije/dyz158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124484PMC
February 2020

Serum ghrelin and esophageal and gastric cancer in two cohorts in China.

Int J Cancer 2020 05 12;146(10):2728-2735. Epub 2019 Aug 12.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Ghrelin is a hormone produced in the oxyntic glands of the stomach. Previous work by our group has suggested that serum ghrelin concentrations are inversely associated with gastric and esophageal cancer risk. We measured ghrelin concentrations in the Linxian General Population Nutrition Intervention Trial (NIT), and the Shanghai Women's Health Study (SWHS). In NIT, we analyzed serum samples from 298 esophageal squamous cell carcinoma (ESCC) cases, 518 gastric cardia adenocarcinoma (GCA) cases, 258 gastric noncardia adenocarcinoma (GNCA) cases and 770 subcohort controls (case-cohort). In SWHS, we measured ghrelin in plasma samples from 249 GNCA cases and 498 matched controls (nested case-control). Ghrelin was measured using radioimmunoassay. In NIT and SWHS, low ghrelin concentrations were associated with an increased risk of developing GNCA and GCA. The hazard ratio (HR ) for GNCA in NIT was 1.35 (95% CI: 0.89-2.05; p-trend = 0.02); the odds ratio in SWHS was 1.66 (95% CI: 1.02-2.70; p-trend = 0.06). Low ghrelin was associated with a twofold increase of GCA (HR = 2.00, 95% CI: 1.45-2.77; p-trend<0.001). In contrast, a lower risk of ESCC (NIT ESCC HR = 0.65, 95% CI: 0.45-0.92; p-trend = 0.02) was found in NIT. Low baseline ghrelin concentrations were associated with an increased risk for GNCA and GCA in the NIT and the SWHS. In contrast, low ghrelin concentrations at baseline were associated with a reduced risk of developing ESCC in the NIT. Ghrelin may be an early marker of future cancer risk for developing upper gastrointestinal cancer in regions of high incidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.32597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477842PMC
May 2020

Tuberculosis infection and lung adenocarcinoma: Mendelian randomization and pathway analysis of genome-wide association study data from never-smoking Asian women.

Genomics 2020 03 12;112(2):1223-1232. Epub 2019 Jul 12.

Guangdong Lung Cancer Institute, Medical Research Center and Cancer Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

We investigated whether genetic susceptibility to tuberculosis (TB) influences lung adenocarcinoma development among never-smokers using TB genome-wide association study (GWAS) results within the Female Lung Cancer Consortium in Asia. Pathway analysis with the adaptive rank truncated product method was used to assess the association between a TB-related gene-set and lung adenocarcinoma using GWAS data from 5512 lung adenocarcinoma cases and 6277 controls. The gene-set consisted of 31 genes containing known/suggestive associations with genetic variants from previous TB-GWAS. Subsequently, we followed-up with Mendelian Randomization to evaluate the association between TB and lung adenocarcinoma using three genome-wide significant variants from previous TB-GWAS in East Asians. The TB-related gene-set was associated with lung adenocarcinoma (p = 0.016). Additionally, the Mendelian Randomization showed an association between TB and lung adenocarcinoma (OR = 1.31, 95% CI: 1.03, 1.66, p = 0.027). Our findings support TB as a causal risk factor for lung cancer development among never-smoking Asian women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygeno.2019.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954985PMC
March 2020

Association between occupational exposure to trichloroethylene and serum levels of microRNAs: a cross-sectional molecular epidemiology study in China.

Int Arch Occup Environ Health 2019 11 3;92(8):1077-1085. Epub 2019 Jun 3.

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.

Objectives: The objective of our study was to evaluate the association between occupational exposure to trichloroethylene (TCE), a suspected lymphomagen, and serum levels of miRNAs in a cross-sectional molecular epidemiology study of TCE-exposed workers and comparable unexposed controls in China.

Methods: Serum levels of 40 miRNAs were compared in 74 workers exposed to TCE (median: 12 ppm) and 90 unexposed control workers. Linear regression models were used to test for differences in serum miRNA levels between exposed and unexposed workers and to evaluate exposure-response relationships across TCE exposure categories using a three-level ordinal variable [i.e., unexposed, < 12 ppm, the median value among workers exposed to TCE) and ≥ 12 ppm)]. Models were adjusted for sex, age, current smoking, current alcohol use, and recent infection.

Results: Seven miRNAs showed significant differences between exposed and unexposed workers at FDR (false discovery rate) < 0.20. miR-150-5p and let-7b-5p also showed significant inverse exposure-response associations with TCE exposure (P= 0.002 and 0.03, respectively). The % differences in serum levels of miR-150-5p relative to unexposed controls were - 13% and - 20% among workers exposed to < 12 ppm and ≥ 12 ppm TCE, respectively.

Conclusions: miR-150-5p is involved in B cell receptor pathways and let-7b-5p plays a role in the innate immune response processes that are potentially important in the etiology of non-Hodgkin lymphoma (NHL). Further studies are needed to replicate these findings and to directly test the association between serum levels of these miRNAs and risk of NHL in prospective studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00420-019-01448-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953905PMC
November 2019

Household coal combustion, indoor air pollutants, and circulating immunologic/inflammatory markers in rural China.

J Toxicol Environ Health A 2019 13;82(6):411-421. Epub 2019 May 13.

a Division of Cancer Epidemiology and Genetics , National Cancer Institute - National Institutes of Health , Rockville , MD , USA.

The study aim was to investigate whether household bituminous ("smoky") coal use and personal exposure to combustion emissions were associated with immunologic/inflammatory marker levels. A cross-sectional study of healthy never-smoking women from rural Xuanwei and Fuyuan, China was conducted, which included 80 smoky coal and 14 anthracite ("smokeless") coal users. Personal exposure to fine particulate matter (PM) and benzo[a]pyrene (BaP) was assessed using portable devices, while 67 circulating plasma immunologic/inflammatory markers were measured using multiplex bead-based assays. Multivariable linear regression models were employed to estimate associations between smoky coal versus smokeless coal use, indoor air pollutants, and immunologic/inflammatory markers. Six markers were altered among smoky coal users compared to smokeless coal, including significantly decreased interferon-inducible T-cell alpha chemoattractant (CXCL11/I-TAC), and increased serum amyloid P component (SAP). CXCL11/I-TAC was previously found to be reduced in workers exposed to high levels of diesel engine exhaust, which exhibits similar constituents as coal combustion emissions. Further, there was evidence that elevated PM and BaP exposure was associated with significantly diminished levels of the serum amyloid A (SAA); however, the false discovery rates (FDRs) were >0.2 after accounting for multiple comparisons. Inflammatory processes may thus mediate the carcinogenic effects attributed to smoky coal emissions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15287394.2019.1614500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594692PMC
May 2020

Prediagnostic blood levels of organochlorines and risk of non-Hodgkin lymphoma in three prospective cohorts in China and Singapore.

Int J Cancer 2020 02 9;146(3):839-849. Epub 2019 May 9.

Division of Cancer Epidemiology and Genetics, NCI, NIH, DHHS, Rockville, MD.

Specific organochlorines (OCs) have been associated with non-Hodgkin lymphoma (NHL) with varying degrees of evidence. These associations have not been evaluated in Asia, where the high exposure and historical environmental contamination of certain OC pesticides (e.g., dichlorodiphenyltrichloroethane [DDT], hexachlorocyclohexane [HCH]) are different from Western populations. We evaluated NHL risk and prediagnostic blood levels of OC pesticides/metabolites and polychlorinated biphenyl congeners in a case-control study of 167 NHL cases and 167 controls nested within three prospective cohorts in Shanghai and Singapore. Conditional logistic regression was used to analyze lipid-adjusted OC levels and NHL risk. Median levels of p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), the primary DDT metabolite, and β-HCH were up to 12 and 65 times higher, respectively, in samples from the Asian cohorts compared to several cohorts in the United States and Norway. An increased risk of NHL was observed among those with higher β-HCH levels both overall (3rd vs. 1st tertile OR = 1.8, 95%CI = 1.0-3.2; p = 0.049) and after excluding cases diagnosed within 2 years of blood collection (3rd vs. 1st tertile OR = 2.0, 95%CI = 1.1-3.9; p = 0.03), and the association was highly consistent across the three cohorts. No significant associations were observed for other OCs, including p,p'-DDE. Our findings provide support for an association between β-HCH blood levels and NHL risk. This is a concern because substantial quantities of persistent, toxic residues of HCH are present in the environment worldwide. Although there is some evidence that DDT is associated with NHL, our findings for p,p'-DDE do not support an association.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.32350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244652PMC
February 2020

Benzene Exposure Response and Risk of Myeloid Neoplasms in Chinese Workers: A Multicenter Case-Cohort Study.

J Natl Cancer Inst 2019 05;111(5):465-474

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD.

Background: 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: 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: 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: 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnci/djy143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681472PMC
May 2019

Lung cancer risk by geologic coal deposits: A case-control study of female never-smokers from Xuanwei and Fuyuan, China.

Int J Cancer 2019 06 15;144(12):2918-2927. Epub 2019 Jan 15.

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.

Coal types vary around the world because of geochemical differences in their source deposits; however, the influence of coal emissions from different deposits on human health remains unexplored. To address this issue, we conducted the first study of the relationship between coal use from various deposits and lung cancer risk in Xuanwei and Fuyuan, counties in China where lung cancer rates are among the highest in the world among female never-smokers due to use of bituminous ("smoky") coal for heating and cooking. We conducted a population-based case-control study of 1031 lung cancer cases and 493 controls among never-smoking women in Xuanwei and Fuyuan. Logistic regression models were used to estimate associations between coal use from various deposits across the lifecourse and lung cancer risk. There was substantial heterogeneity in risks by coal deposit (p = 7.8E-05). Compared to non-smoky coal users, risks by smoky coal deposit ranged from OR = 7.49 (95% CI: 3.43-16.38) to OR = 33.40 (95% CI: 13.07-85.34). Further, women born into homes that used smoky coal and subsequently changed to non-smoky coal had a higher risk (OR = 10.83 (95% CI: 4.61-25.46)) than women born into homes that used non-smoky coal and changed to smoky coal (OR = 4.74 (95% CI: 2.03-11.04, p = 0.04)). Our study demonstrates that various sources of coal have considerably different impact on lung cancer in this population and suggests that early-life exposure to carcinogenic emissions may exert substantial influence on health risks later in life. These factors should be considered when evaluating the health risks posed by exposure to coal combustion emissions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.32034DOI Listing
June 2019

Green tea consumption and risk of type 2 diabetes in Chinese adults: the Shanghai Women's Health Study and the Shanghai Men's Health Study.

Int J Epidemiol 2018 12;47(6):1887-1896

Division of Epidemiology, Vanderbilt University School of Medicine, Nashville, TN, USA.

Background: Epidemiological evidence on the association between tea consumption and the risk of type 2 diabetes (T2D) is inconsistent. This study prospectively investigated whether green tea drinking affects the risk of T2D.

Methods: This study included participants from the Shanghai Women's Health Study (N = 67 058) and the Shanghai Men's Health Study (N  =  52 315) without diabetes at study enrolment. Details of tea consumption, including types and amounts, were collected at the baseline and follow-up survey. Incident T2D was identified through follow-up surveys. Plasma level of caffeine metabolite was measured in a nested case-control study involving 592 diabetes case-control pairs. Cox regression analysis, with tea drinking as a time-dependent variable and covariates adjusted for by a propensity score, was applied to estimate the hazard ratio (HR) and 95% confidence interval (CI) for T2D risk. Logistic regression analysis was applied to evaluate the association between caffeine metabolites and T2D risk.

Results: Current green tea drinkers had an increased risk of T2D compared with non-current drinkers [HR = 1.20 (95% CI = 1.14-1.27)], and a dose-response relationship was observed for duration of drinking tea and the amount of tea consumed [P for trend <0.001]. The increased risk associated with green tea drinking was observed in both women and men, across the entire period of follow-up, with HR (95% CI) of 1.08 (0.97-1.19) within 5 years of follow-up, 1.22 (1.12-1.32) during the period of 5-10 years of follow-up and 1.16 (1.03-1.30) after 10 years of follow-up. This association did not vary significantly by body mass index, waist-to-hip circumference ratio or smoking status. Plasma level of caffeine was also associated with increased diabetes risk (P  =  0.03), confirming the results based on self-reported tea drinking.

Conclusions: Green tea drinking was associated with an increased risk of T2D in Chinese adults. The mechanisms underlying the association need to be elucidated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ije/dyy173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280927PMC
December 2018

Variants in genes encoding small GTPases and association with epithelial ovarian cancer susceptibility.

PLoS One 2018 6;13(7):e0197561. Epub 2018 Jul 6.

Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality in American women. Normal ovarian physiology is intricately connected to small GTP binding proteins of the Ras superfamily (Ras, Rho, Rab, Arf, and Ran) which govern processes such as signal transduction, cell proliferation, cell motility, and vesicle transport. We hypothesized that common germline variation in genes encoding small GTPases is associated with EOC risk. We investigated 322 variants in 88 small GTPase genes in germline DNA of 18,736 EOC patients and 26,138 controls of European ancestry using a custom genotype array and logistic regression fitting log-additive models. Functional annotation was used to identify biofeatures and expression quantitative trait loci that intersect with risk variants. One variant, ARHGEF10L (Rho guanine nucleotide exchange factor 10 like) rs2256787, was associated with increased endometrioid EOC risk (OR = 1.33, p = 4.46 x 10-6). Other variants of interest included another in ARHGEF10L, rs10788679, which was associated with invasive serous EOC risk (OR = 1.07, p = 0.00026) and two variants in AKAP6 (A-kinase anchoring protein 6) which were associated with risk of invasive EOC (rs1955513, OR = 0.90, p = 0.00033; rs927062, OR = 0.94, p = 0.00059). Functional annotation revealed that the two ARHGEF10L variants were located in super-enhancer regions and that AKAP6 rs927062 was associated with expression of GTPase gene ARHGAP5 (Rho GTPase activating protein 5). Inherited variants in ARHGEF10L and AKAP6, with potential transcriptional regulatory function and association with EOC risk, warrant investigation in independent EOC study populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197561PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6034790PMC
December 2018

Serologic markers of viral infection and risk of non-Hodgkin lymphoma: A pooled study of three prospective cohorts in China and Singapore.

Int J Cancer 2018 08 6;143(3):570-579. Epub 2018 Apr 6.

Division of Cancer Epidemiology and Genetics, NCI, NIH, DHHS, Rockville, MD.

Incidence rates of non-Hodgkin lymphoma (NHL) and distributions of certain viruses differ between East Asian and Western populations. There are limited data on associations between serologic markers of multiple viral infections in pre-diagnostic blood and NHL risk in East Asians. We conducted a nested case-control study of 214 NHL cases and 214 matched controls from three population-based prospective cohorts in Shanghai and Singapore. Antibodies against antigens from herpesviruses, Hepatitis B (HBV) and C (HCV) virus and polyomaviruses were measured in plasma or serum using fluorescent bead-based multiplex assays. Conditional logistic regression was used to evaluate associations between antibody levels and NHL risk. An increased risk of NHL was observed for higher compared to lower EA-D (Odds Ratio (OR) = 2.04, 95% Confidence Interval (CI) = 1.10-3.81; p  = 0.005) and ZEBRA (OR = 2.17, 95% CI = 0.96-4.89; p  = 0.008) Epstein-Barr Virus (EBV) antibodies, as well as for antibody seropositivity against the IE1A human herpesvirus-6 (HHV-6) antigen (OR = 1.85, 95% CI = 1.04-3.29). An increased NHL risk was also observed for higher compared to lower antibodies against the HBV-HBc and HBe antigens. An increased risk of NHL in relation to EBV and HBV infection in East Asians is consistent with findings in several studies of Western populations, suggesting similar viral risk factors for NHL in these diverse populations with distinct patterns of NHL. The association between HHV-6 antibodies and NHL has not previously been reported in a prospective study in this population and will require replication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.31385DOI Listing
August 2018

Blood Biomarkers and Gastric Cancer Survival in China.

Cancer Epidemiol Biomarkers Prev 2018 03 20;27(3):342-344. Epub 2017 Dec 20.

Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.

Infection with is the leading risk factor for noncardia gastric cancer, yet its influence on prognosis of gastric cancer is largely unknown. Thus, exploring the role of () in survival could lead to a greater understanding of the high mortality associated with gastric cancer. Seropositivity to 15 antigens was assessed using a multiplex assay in two prospective cohorts, the Shanghai Men's Health Study and the Shanghai Women's Health Study. Multivariable-adjusted Cox proportional hazards regression was used to examine the association between prediagnostic antigen levels and gastric cancer-specific survival. Prediagnostic levels of serum antibodies that were previously associated with gastric cancer incidence in this population were not associated with gastric cancer survival, whether assessed in a 6-antigen panel [HR = 1.29; 95% confidence interval (CI), 0.78-2.13 for men; HR = 0.93; 95% CI, 0.57-1.52 for women], focused on CagA (HR = 0.73; 95% CI, 0.44-1.20 forwomen; HR = 1.27; 95% CI, 0.70-2.31 for men) or on the high-risk biomarkers of dual Omp and HP 0305 seropositivity (HR = 0.97; 95% CI, 0.72-1.30 for women; HR = 1.37; 95% CI, 0.97-1.94 for men). Prediagnostic antigen levels are not associated with gastric cancer survival in East Asian populations. Identification of additional factors associated with gastric cancer survival would further our understanding of the high mortality associated with this malignancy. .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-17-1084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835187PMC
March 2018

Association of sleep duration and incidence of diabetes modified by tea consumption: a report from the Shanghai men's health study.

Sleep Med 2017 Oct 6;38:135-141. Epub 2017 Sep 6.

Division of Epidemiology, Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.

Objectives: To evaluate the association between sleep duration and the incidence of diabetes stratified by sleep-related factors among Chinese men.

Methods: This study included 34,825 men who provided information on sleep-related questions in the Shanghai Men's Health Study, a population-based cohort study conducted in Shanghai, China from 2002 to 2011. Participants were excluded who had a history of diabetes or who were diagnosed with diabetes within 2 years of recruitment. Cox regression was employed to evaluate the influence of sleep duration and its interaction with sleep-related factors on diabetes risk.

Results: A total of 1521 incident cases were documented during a median of 5.6 follow-up years. Adjusted hazard ratios and 95% confidence intervals were 1.0 (0.9-1.1) and 1.2 (1.0-1.3) for men who slept <7 and ≥8 h per day, respectively, compared with those who slept 7 h per day (p = 0.01). Stratified analyses revealed that the association between sleep duration and risk of diabetes was only statistically significant among current smokers and regular drinkers, never tea drinkers, men with a high body mass index, hypertension or comorbidity, and men who did not work nightshift or who snored. A statistically significant interaction between tea drinking and sleep duration was observed (p = 0.01). The above association patterns remained when daytime nappers were excluded from the analyses.

Conclusions: The data suggested that longer sleep duration, particularly among individuals already exhibiting factors linked to poor quality of sleep, was associated with diabetes. The association between sleep duration and diabetes may be modified by tea drinking, especially in older men or men with more sleep-related factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.sleep.2017.07.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5659744PMC
October 2017

A prospective study of immune and inflammation markers and risk of lung cancer among female never smokers in Shanghai.

Carcinogenesis 2017 10;38(10):1004-1010

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.

There is a paucity of data on risk factors for lung cancer among never smokers. Here, we have carried out the first large study of circulating inflammation markers and lung cancer risk among female never smokers in Shanghai. A study of 248 lung cancer cases in female never smokers and 263 controls was nested within the Shanghai Women's Health Study (n = 75221), matched by dates of birth and blood collection (mean follow-up time = 7.5 years). Prediagnostic plasma levels of 65 inflammation markers were measured using a Luminex bead-based assay. Odds ratios (ORs) were estimated with multivariable logistic regression. Nine of 61 evaluable markers were statistically significantly associated with lung cancer risk among never smoking Chinese women (P-trend across categories <0.05). Soluble interleukin-6 receptor [sIL-6R; highest versus lowest category OR = 2.37; 95% confidence interval (CI) 1.40-4.02) and chemokine (C-C motif) ligand 2/monocyte chemotactic protein 1; (OR = 1.62; 95% CI 0.94-2.80) were associated with an increased risk of lung cancer, whereas interleukin (IL)-21 (OR = 0.53; 95%CI 0.31-0.93), chemokine (C-X3-C motif) ligand 1/fractalkine (OR = 0.54; 95% CI 0.30-0.96), soluble vascular endothelial growth factor receptor 2 (sVEGFR2, OR = 0.45; 95% CI 0.26-0.76), sVEGFR3 (OR = 0.53; 95% CI 0.32-0.90), soluble tumor necrosis factor receptor I (OR = 0.49; 95% CI 0.29-0.83), IL-10 (OR = 0.60; 95% CI 0.34-1.05) and C-reactive protein (OR = 0.63; 95% CI 0.37-1.06) were associated with a decreased risk. sIL-6R remained significantly associated with lung cancer risk >7.5 years prior to diagnosis. Markers involved in various aspects of the immune response were associated with subsequent lung cancer risk, implicating inflammation in the etiology of lung cancer among female never smokers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/carcin/bgx075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862245PMC
October 2017

Personal exposure to fine particulate matter and benzo[a]pyrene from indoor air pollution and leukocyte mitochondrial DNA copy number in rural China.

Carcinogenesis 2017 09;38(9):893-899

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services, Rockville, MD, 20850, USA.

Households in Xuanwei and Fuyuan, China, possess hazardous levels of fine particulate matter with an aerodynamic diameter <2.5 microns (PM2.5) and polycyclic aromatic hydrocarbons (PAHs) from coal combustion. Previous studies found that increased exposure to PM2.5 and benzo[a]pyrene (BaP; a PAH) were associated with decreased mitochondrial DNA copy number (mtDNAcn), a marker of oxidative stress. We further evaluated these associations in a cross-sectional study of 148 healthy non-smoking women from Xuanwei and Fuyuan. Personal exposure to PM2.5 and BaP was measured using portable devices. MtDNAcn was measured using qPCR amplification of leukocyte DNA that was collected after air measurements. Linear regression models were used to estimate the associations between personal exposure to PM2.5 and BaP, and mtDNAcn adjusted for age, body mass index (BMI) and fuel type. We found inverse associations between exposure to PM2.5 and BaP, and mtDNAcn. Each incremental log-μg/m3 increase in PM2.5 was associated with a significant decrease in mtDNAcn of -10.3 copies per cell [95% confidence interval (95% CI): -18.6, -2.0; P = 0.02]. Additionally, each log-ng/m3 increase in BaP was associated with a significant decrease in mtDNAcn of -5.4 copies per cell (95% CI: -9.9, -0.8, P = 0.02). Age, BMI, fuel type and coal mine type were not significantly associated with mtDNAcn. Exposure to PM2.5 and BaP may alter mitochondrial dynamics in non-smoking Chinese women. MtDNAcn may be a potential mediator of indoor air pollution on chronic disease development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/carcin/bgx068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862333PMC
September 2017

Evaluating Exposure-Response Associations for Non-Hodgkin Lymphoma with Varying Methods of Assigning Cumulative Benzene Exposure in the Shanghai Women's Health Study.

Ann Work Expo Health 2017 01;61(1):56-66

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rm. 6E634, Rockville, MD 20850, USA.

Objectives: To provide insight into the contributions of exposure measurements to job exposure matrices (JEMs), we examined the robustness of an association between occupational benzene exposure and non-Hodgkin lymphoma (NHL) to varying exposure assessment methods.

Methods: NHL risk was examined in a prospective population-based cohort of 73087 women in Shanghai. A mixed-effects model that combined a benzene JEM with >60000 short-term, area benzene inspection measurements was used to derive two sets of measurement-based benzene estimates: 'job/industry-specific' estimates (our presumed best approach) were derived from the model's fixed effects (year, JEM intensity rating) and random effects (occupation, industry); 'calibrated JEM' estimates were derived using only the fixed effects. 'Uncalibrated JEM' (using the ordinal JEM ratings) and exposure duration estimates were also calculated. Cumulative exposure for each subject was calculated for each approach based on varying exposure definitions defined using the JEM's probability ratings. We examined the agreement between the cumulative metrics and evaluated changes in the benzene-NHL associations.

Results: For our primary exposure definition, the job/industry-specific estimates were moderately to highly correlated with all other approaches (Pearson correlation 0.61-0.89; Spearman correlation > 0.99). All these metrics resulted in statistically significant exposure-response associations for NHL, with negligible gain in model fit from using measurement-based estimates. Using more sensitive or specific exposure definitions resulted in elevated but non-significant associations.

Conclusions: The robust associations observed here with varying benzene assessment methods provide support for a benzene-NHL association. While incorporating exposure measurements did not improve model fit, the measurements allowed us to derive quantitative exposure-response curves.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/annweh/wxw009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363053PMC
January 2017

Sleep Duration across the Adult Lifecourse and Risk of Lung Cancer Mortality: A Cohort Study in Xuanwei, China.

Cancer Prev Res (Phila) 2017 Jun 4;10(6):327-336. Epub 2017 Apr 4.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland.

Sufficient sleep duration is crucial for maintaining normal physiological function and has been linked to cancer risk; however, its contribution to lung cancer mortality is unclear. Therefore, we evaluated the relationship between average sleep duration in various age-periods across the adult lifecourse, and risk of lung cancer mortality in Xuanwei, China. An ambidirectional cohort study was conducted in 42,422 farmers from Xuanwei, China. Participants or their surrogates were interviewed in 1992 to assess average sleep hours in the age periods of 21-30, 31-40, 41-50, 51-60, 61-70, and ≥71 years, which were categorized as ≤7, 8 (reference), 9, and ≥10 hours/day. Vital status was followed until 2011. Sex-specific Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for lung cancer mortality in 1994-2011, adjusted for demographic, anthropometric, medical, and household characteristics. J-shaped relationships were found between average sleep duration and lung cancer mortality. The patterns were consistent across sex, age periods, and fuel usage. Compared with sleeping 8 hours/day on average, ≤7 hours/day was associated with significantly increased HRs ranging from 1.39 to 1.58 in ages ≥41 years in men, and 1.29 to 2.47 in ages ≥51 years in women. Furthermore, sleeping ≥10 hours/day was associated with significantly increased HRs ranging from 2.44 to 3.27 in ages ≥41 year in men, and 1.31 to 2.45 in ages ≤60 years in women. Greater and less than 8 hours/day of sleep in various age-periods may be associated with elevated risk of lung cancer mortality in Xuanwei, China. .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1940-6207.CAPR-16-0295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464364PMC
June 2017

Lung cancer risk in welders and foundry workers with a history of heavy smoking in the USA: The National Lung Screening Trial.

Occup Environ Med 2017 06 9;74(6):440-448. Epub 2017 Jan 9.

Division of Cancer Epidemiology and Genetics, Occupational and Environmental Epidemiology Branch, National Cancer Institute, Rockville, Maryland, USA.

Objectives: Foundry work is a risk factor for lung cancer; however, the association with welding is unclear, as smoking is common among metalworkers and may mask the relationship. We evaluated whether history of welding and foundry work, independently and jointly, and employment duration were associated with lung cancer risk in heavy smokers.

Methods: We analysed data from the National Lung Screening Trial, a prospective randomised trial of 53 454 heavy smokers (>30 pack-years) in the USA. Cox regression models were used to estimate the HRs and 95% CIs of medically/histologically confirmed incident lung cancer during the follow-up period (2002-2009) in relation to history and duration of welding and foundry work assessed via questionnaires, adjusted for screening arm, component study, sex, age, race/ethnicity, education, smoking status and pack-years, body mass index and personal/family medical history.

Results: There were 2034 incident lung cancer cases throughout the follow-up. Increasing years of employment in welding (p-trend =0.039) and foundry work (p-trend =0.005) were related to increased lung cancer risk among heavy smokers. Having ever been employed (≥1 yr) as either a welder or foundry worker alone was associated with non-significant increased risks of lung cancer (HR=1.12 (95% CI 0.91 to 1.37) and HR=1.09 (95% CI 0.85 to 1.39), respectively). Further, there was a joint-effect in that those who were ever employed in both occupations had significantly increased risks (HR=1.48 (95% CI 1.08 to 2.04)).

Conclusions: Our findings provide further evidence that exposure to welding/metal fumes may be associated with elevated lung cancer risk.

Trial Registration Number: NCT00047385.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/oemed-2016-104168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400285PMC
June 2017

Association between GWAS-identified lung adenocarcinoma susceptibility loci and EGFR mutations in never-smoking Asian women, and comparison with findings from Western populations.

Hum Mol Genet 2017 01;26(2):454-465

Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.

To evaluate associations by EGFR mutation status for lung adenocarcinoma risk among never-smoking Asian women, we conducted a meta-analysis of 11 loci previously identified in genome-wide association studies (GWAS). Genotyping in an additional 10,780 never-smoking cases and 10,938 never-smoking controls from Asia confirmed associations with eight known single nucleotide polymorphisms (SNPs). Two new signals were observed at genome-wide significance (P < 5 × 10-8), namely, rs7216064 (17q24.3, BPTF), for overall lung adenocarcinoma risk, and rs3817963 (6p21.3, BTNL2) which is specific to cases with EGFR mutations. In further sub-analyses by EGFR status, rs9387478 (ROS1/DCBLD1) and rs2179920 (HLA-DPB1) showed stronger estimated associations in EGFR-positive compared to EGFR-negative cases. Comparison of the overall associations with published results in Western populations revealed that the majority of these findings were distinct, underscoring the importance of distinct contributing factors for smoking and non-smoking lung cancer. Our results extend the catalogue of regions associated with lung adenocarcinoma in non-smoking Asian women and highlight the importance of how the germline could inform risk for specific tumour mutation patterns, which could have important translational implications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/ddw414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856088PMC
January 2017

Menstrual and Reproductive Factors, Hormone Use, and Risk of Pancreatic Cancer: Analysis From the International Pancreatic Cancer Case-Control Consortium (PanC4).

Pancreas 2016 11;45(10):1401-1410

From the *Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain; †Department of Epidemiology, Shanghai Cancer Institute and Jiao Tong University, Shanghai, China; ‡Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY; §Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI; ∥Public Health, Women's and Children's Hospital, Adelaide, SA, Australia; ¶University of California, San Francisco, San Francisco, CA; #National Institute for Public Health and the Environment (RIVM), Bilthoven; **Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands; ††Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; ‡‡Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; §§Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Institute and MF MU, Brno, Czech Republic; ∥∥University Health Network, Department of Surgery, University of Toronto, Toronto, Canada; ¶¶Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University in Prague, Prague; ##Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc, Czech Republic; ***National Cancer Institute, Bethesda, MD; †††Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; ‡‡‡Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; §§§Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Greece; ∥∥∥Department of Epidemiology, Harvard School of Public Health, Boston, MA; ¶¶¶M.D. Anderson Cancer Center, University of Texas, Houston, TX; ###Dalla Lana School of Public Health, University of Toronto, Toronto, Canada; ****Unit of Epidemiology and Biostatistics, CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy; ††††Cancer Center and Institute of Oncology, Warsaw, Poland; and ‡‡‡‡Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT.

Objectives: We aimed to evaluate the relation between menstrual and reproductive factors, exogenous hormones, and risk of pancreatic cancer (PC).

Methods: Eleven case-control studies within the International Pancreatic Cancer Case-control Consortium took part in the present study, including in total 2838 case and 4748 control women. Pooled estimates of odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using a 2-step logistic regression model and adjusting for relevant covariates.

Results: An inverse OR was observed in women who reported having had hysterectomy (ORyesvs.no, 0.78; 95% CI, 0.67-0.91), remaining significant in postmenopausal women and never-smoking women, adjusted for potential PC confounders. A mutually adjusted model with the joint effect for hormone replacement therapy (HRT) and hysterectomy showed significant inverse associations with PC in women who reported having had hysterectomy with HRT use (OR, 0.64; 95% CI, 0.48-0.84).

Conclusions: Our large pooled analysis suggests that women who have had a hysterectomy may have reduced risk of PC. However, we cannot rule out that the reduced risk could be due to factors or indications for having had a hysterectomy. Further investigation of risk according to HRT use and reason for hysterectomy may be necessary.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065728PMC
http://dx.doi.org/10.1097/MPA.0000000000000635DOI Listing
November 2016

Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer.

Oncotarget 2016 10;7(43):69097-69110

Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.

Background: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer.

Methods: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients.

Results: The most significant global associations for all genes in the pathway were seen in endometrioid ( p = 0.082) and clear cell ( p = 0.083), with the most significant gene level association seen with TGFBR2 ( p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 ( p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA ( p = 0.035, endometrioid and mucinous), LGALS1 ( p = 0.03, mucinous), STAT5B ( p = 0.022, clear cell), TGFBR1 ( p = 0.021 endometrioid) and TGFBR2 ( p = 0.017 and p = 0.025, endometrioid and mucinous, respectively).

Conclusions: Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.10215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340115PMC
October 2016
-->