Bryan A. Bassig

Longer telomere length in peripheral white blood cells is associated with risk of lung cancer and the rs2736100 (CLPTM1L-TERT) polymorphism in a prospective cohort study among women in China.

A recent genome-wide association study of lung cancer among never-smoking females in Asia demonstrated that the rs2736100 polymorphism in the TERT-CLPTM1L locus on chromosome 5p15.33 was strongly and significantly associated with risk of adenocarcinoma of the lung. The telomerase gene TERT is a reverse transcriptase that is critical for telomere replication and stabilization by controlling telomere length. We previously found that longer telomere length measured in peripheral white blood cell DNA was associated with increased risk of lung cancer in a prospective cohort study of smoking males in Finland. To follow up on this finding, we carried out a nested case-control study of 215 female lung cancer cases and 215 female controls, 94% of whom were never-smokers, in the prospective Shanghai Women’s Health Study cohort. There was a dose-response relationship between tertiles of telomere length and risk of lung cancer (odds ratio (OR), 95% confidence interval [CI]: 1.0, 1.4 [0.8–2.5], and 2.2 [1.2–4.0], respectively; P trend = 0.003). Further, the association was unchanged by the length of time from blood collection to case diagnosis. In addition, the rs2736100 G allele, which we previously have shown to be associated with risk of lung cancer in this cohort, was significantly associated with longer telomere length in these same study subjects (P trend = 0.030). Our findings suggest that individuals with longer telomere length in peripheral white blood cells may have an increased risk of lung cancer, but require replication in additional prospective cohorts and populations.

Telomere Length in White Blood Cell DNA and Lung Cancer: A Pooled Analysis of Three Prospective Cohorts

We investigated the relationship between telomere length and lung cancer in a pooled analysis from three prospective cohort studies: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, conducted among men and women in the United States, and previously published data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Trial conducted among male smokers in Finland, and the Shanghai Womens Health Study (SWHS), which is comprised primarily of never-smokers. The pooled population included 847 cases and 847 controls matched by study, age, and sex. Leukocyte telomere length was measured by a monochrome multiplex qPCR assay. We used conditional logistic regression models to calculate ORs and their 95% confidence intervals (CI) for the association between telomere length and lung cancer risk, adjusted for age and pack-years of smoking. Longer telomere length was associated with increased lung cancer risk in the pooled analysis [OR (95% CI) by quartile: 1.00; 1.24 (0.90-1.71); 1.27 (0.91-1.78); and 1.86 (1.33-2.62); P trend = 0.000022]. Findings were consistent across the three cohorts and strongest for subjects with very long telomere length, i.e., lung cancer risks for telomere length [OR (95% CI)] in the upper half of the fourth quartile were 2.41 (1.28-4.52), 2.16 (1.11-4.23), and 3.02(1.39-6.58) for the PLCO trial, the ATBC trial, and the SWHS, respectively. In addition, the association persisted among cases diagnosed more than 6 years after blood collection and was particularly evident for female adenocarcinoma cases. Telomere length in white blood cell DNA may be a biomarker of future increased risk of lung cancer in diverse populations.

Personal and Indoor PM2.5 Exposure from Burning Solid Fuels in Vented and Unvented Stoves in a Rural Region of China with a High Incidence of Lung Cancer

The combustion of biomass and coal is the dominant source of household air pollution (HAP) in China, and contributes significantly to the total burden of disease in the Chinese population. To characterize HAP exposure related to solid fuel use and ventilation patterns, an exposure assessment study of 163 nonsmoking female heads of households enrolled from 30 villages was conducted in Xuanwei and Fuyuan, two neighboring rural counties with high incidence of lung cancer due to the burning of smoky coal (a bituminous coal, which in health evaluations is usually compared to smokeless coal—an anthracite coal available in some parts of the area). Personal and indoor 24-h PM2.5 samples were collected over two consecutive days in each household, with approximately one-third of measurements retaken in a second season. The overall geometric means (GM) of personal PM2.5 concentrations in Xuanwei and Fuyuan were 166 [Geometric Standard Deviation (GSD):2.0] and 146 (GSD:1.9) μg/m3, respectively, which were similar to the indoor PM2.5 air concentrations [GM(GSD):162 (2.1) and 136 (2.0) μg/m3, respectively]. Personal PM2.5 was moderately highly correlated with indoor PM2.5 (Spearman r = 0.70, p < 0.0001). Burning wood or plant materials (tobacco stems, corncobs etc.) resulted in the highest personal PM2.5 concentrations (GM:289 and 225 μg/m3, respectively), followed by smoky coal, and smokeless coal (GM:148 and 115 μg/m3, respectively). PM2.5 levels of vented stoves were 34–80% lower than unvented stoves and firepits across fuel types. Mixed effect models indicated that fuel type, ventilation, number of windows, season, and burning time per stove were the main factors related to personal PM2.5 exposure. Lower PM2.5 among vented stoves compared with unvented stoves and firepits is of interest as it parallels the observation of reduced risks of malignant and nonmalignant lung diseases in the region.

Short-term effects of air pollution on daily mortality and years of life lost in Nanjing, China

The deteriorating air quality in Chinese cities is attracting growing public concern. We conducted analyses to quantify the associations between daily changes in ambient air pollution and mortality in Nanjing, China. Daily mortality, air pollution, and meteorological data from 1 January 2009 to 31 December 2013 were collected. Over-dispersed Poisson regression models were used to evaluate the risk of daily non-accidental mortality and years of life lost (YLL) from exposure to respirable particulate matter (PM10) and gaseous pollutants (NO2, SO2). Stratified analysis was conducted to indentify the modifying effect of individual-level factors on the association between air pollutants and mortality. We found that interquartile range (IQR) increases in the two-day average of PM10, NO2 and SO2 were significantly associated with 1.6% [95% confidence interval (CI):0.7%-2.6%], 2.9% (95% CI: 1.7%-4.2%) and 2.4% (95% CI: 1.2%-3.6%) higher rates of non-accidental mortality; and related to YLL increases of 20.5 (95% CI: 6.3-34.8), 34.9 (95% CI: 16.9-52.9) and 30.3 (95% CI: 12.2-48.4) years, respectively; Associations between air pollution and mortality were more pronounced in the warm season than in the cool season. We conclude that the risks of mortality and YLL were elevated corresponding to an increase in current ambient concentrations of the air pollutants, and season may modify the effects of outdoor air pollution in Nanjing.

Current Understanding of Lifestyle and Environmental Factors and Risk of Non-Hodgkin Lymphoma: An Epidemiological Update

The incidence rates of non-Hodgkin lymphoma (NHL) have steadily increased over the last several decades in the United States, and the temporal trends in incidence can only be partially explained by the HIV epidemic. In 1992, an international workshop sponsored by the United States National Cancer Institute concluded that there was an “emerging epidemic” of NHL and emphasized the need to investigate the factors responsible for the increasing incidence of this disease. Over the past two decades, numerous epidemiological studies have examined the risk factors for NHL, particularly for putative environmental and lifestyle risk factors, and international consortia have been established in order to investigate rare exposures and NHL subtype-specific associations. While few consistent risk factors for NHL aside from immunosuppression and certain infectious agents have emerged, suggestive associations with several lifestyle and environmental factors have been reported in epidemiologic studies. Further, increasing evidence has suggested that the effects of these and other exposures may be limited to or stronger for particular NHL subtypes. This paper examines the progress that has been made over the last twenty years in elucidating the etiology of NHL, with a primary emphasis on lifestyle factors and environmental exposures.

A Case-Control Study of Prenatal Thallium Exposure and Low Birth Weight in China.

Background Thallium (Tl) is a highly toxic heavy metal widely present in the environment. Case reports have suggested that maternal exposure to high levels of Tl during pregnancy is associated with low birth weight (LBW), but epidemiological data are limited. Objectives This study was designed to evaluate whether prenatal Tl exposure is associated with an increased risk of LBW. Methods This case–control study involving 816 study participants (204 LBW cases and 612 matched controls) was conducted in Hubei Province, China, in 2012–2014. Tl concentrations were measured in maternal urine collected at delivery, and associations with LBW were evaluated using conditional logistic regression. Results Higher maternal urinary Tl levels were significantly associated with increased risk of LBW [crude odds ratio (OR) = 1.52; 95% CI: 1.00, 2.30 for the highest vs. lowest tertile], and the association was similarly elevated after adjustment for potential confounders (adjusted OR = 1.90; 95% CI: 1.01, 3.58 for the highest vs. lowest tertile). Stratified analyses showed slightly higher risk estimates for LBW associated with higher Tl levels for mothers < 28 years old and for mothers with lower household income; however, there was no statistical evidence of heterogeneity in risk according to maternal age (p for heterogeneity = 0.18) or household income (p for heterogeneity = 0.28). Conclusion To our knowledge, ours is the first case–control study to investigate the association between prenatal Tl exposure and LBW. The results suggest that prenatal exposure to high levels of Tl may be associated with an increased risk of LBW. Citation Xia W, Du X, Zheng T, Zhang B, Li Y, Bassig BA, Zhou A, Wang Y, Xiong C, Li Z, Yao Y, Hu J, Zhou Y, Liu J, Xue W, Ma Y, Pan X, Peng Y, Xu S. 2016. A case–control study of prenatal thallium exposure and low birth weight in China. Environ Health Perspect 124:164–169; http://dx.doi.org/10.1289/ehp.1409202

Home kitchen ventilation, cooking fuels, and lung cancer risk in a prospective cohort of never smoking women in Shanghai, China

Indoor air pollution (IAP) caused by cooking has been associated with lung cancer risk in retrospective case–control studies in developing and rural countries. We report the association of cooking conditions, fuel use, oil use, and risk of lung cancer in a developed urban population in a prospective cohort of women in Shanghai. A total of 71,320 never smoking women were followed from 1996 through 2009 and 429 incident lung cancer cases were identified. Questionnaires collected information on household living and cooking practices for the three most recent residences and utilization of cooking fuel and oil, and ventilation conditions. Cox proportional hazards regression estimated the association for kitchen ventilation conditions, cooking fuels, and use of cooking oils for the risk of lung cancer by hazard ratios (HR) with 95% confidence intervals (95% CI). Ever poor kitchen ventilation was associated with a 49% increase in lung cancer risk (HR: 1.49; 95% CI: 1.15–1.95) compared to never poor ventilation. Ever use of coal was not significantly associated. However, ever coal use with poor ventilation (HR: 1.69; 95% CI: 1.22–2.35) and 20 or more years of using coal with poor ventilation (HR: 2.03; 95% CI: 1.35–3.05) was significantly associated compared to no exposure to coal or poor ventilation. Cooking oil use was not significantly associated. These results demonstrate that IAP from poor ventilation of coal combustion increases the risk of lung cancer and is an important public health issue in cities across China where people may have lived in homes with inadequate kitchen ventilation.

Smoky coal, tobacco smoking, and lung cancer risk in Xuanwei, China

OBJECTIVES Lung cancer rates in Xuanwei are the highest in China. In-home use of smoky coal has been associated with lung cancer risk, and the association of smoking and lung cancer risk strengthened after stove improvement. Here, we explored the differential association of tobacco use and lung cancer risk by the intensity, duration, and type of coal used. MATERIALS AND METHODS We conducted a population-based case-control study of 260 male lung cancer cases and 260 age-matched male controls. Odds ratios (OR) and 95% confidence interval (CI) for tobacco use was calculated by conditional logistic regression. RESULTS Use of smoky coal was significantly associated with an increased risk of lung cancer, and tobacco use was weakly and non-significantly associated with lung cancer risk. When the association was assessed by coal use, the cigarette-lung cancer risk association was null in hazardous coal users and elevated in less hazardous smoky coal users and non-smoky coal users. The risk of lung cancer per cigarette per day decreased as annual use of coal increased (>0-3 tons: OR: 1.09; 95% CI: 1.03-1.17; >3 tons: OR: 0.99; 95% CI: 0.95-1.03). Among more hazardous coal users, attenuation occurred at even low levels of usage (>0-3 tons: OR: 1.02; 95% CI: 0.91-1.14; >3 tons: OR: 0.94; 95% CI: 0.97-1.03). CONCLUSION We found evidence that smoky coal attenuated the tobacco and lung cancer risk association in males that lived in Xuanwei, particularly among users of hazardous coal where even low levels of smoky coal attenuated the association. Our results suggest that the adverse effects of tobacco may become more apparent as Chinas population continues to switch to cleaner fuels for the home, underscoring the urgent need for smoking cessation in China and elsewhere.

Occupational trichloroethylene exposure and risk of lymphatic and haematopoietic cancers: a meta-analysis

The carcinogenic potential of trichloroethylene (TCE) continues to generate much controversy, even after the US Environmental Protection Agency raised its classification to ‘carcinogenic to humans’. We conducted a meta-analysis of published cohort and case–control studies exploring occupational TCE exposure in relation to five different lymphatic and haematopoietic cancers: non-Hodgkins lymphoma (NHL, N=24), Hodgkins lymphoma (HL, N=13), multiple myeloma (MM, N=11), leukaemia (N=12) and chronic/small lymphocytic leukaemia (CLL/SLL, N=7). Studies published between 1950 and 2011 were identified through a PubMed Medline search. All studies included in analyses were classified as those that assessed either occupational TCE exposure specifically (‘TCE-exposure’ studies) or a broader classification of all chlorinated solvents (‘chlorinated solvent-exposure’ studies). A significantly raised summary estimate for NHL was seen for all cohort and case–control ‘TCE-exposure’ studies combined (N=19; relative risk (RR)=1.32, 95% CI 1.14 to 1.54; I2=25.20; p-heterogeneity=0.12) and for cohort ‘TCE-exposure’ studies (N=10; RR=1.52, 95% CI 1.29 to 1.79; I2=7.09; p-heterogeneity=0.63). A non-significant but raised summary estimate was seen for NHL case–control ‘TCE-exposure’ studies. No significant association with NHL risk was detected overall for any ‘chlorinated solvent-exposure’ studies. Summary estimates for occupational TCE exposure were not associated with risk of HL, MM, leukaemia or CLL/SLL. Our updated meta-analysis of NHL, which incorporates new analytical results from three cohort and four case–control studies, supports an association between occupational TCE exposure and NHL.

Effects of Environmental Exposures on Fetal and Childhood Growth Trajectories

Delayed fetal growth and adverse birth outcomes are some of the greatest public health threats to this generation of children worldwide because these conditions are major determinants of mortality, morbidity, and disability in infancy and childhood and are also associated with diseases in adult life. A number of studies have investigated the impacts of a range of environmental conditions during pregnancy (including air pollution, endocrine disruptors, persistent organic pollutants, heavy metals) on fetal and child development. The results, while provocative, have been largely inconsistent. This review summarizes up to date epidemiologic studies linking major environmental pollutants to fetal and child development and suggested future directions for further investigation.