Gong Yang

Household air pollution (HAP) is of public health concern, with ~3 billion people worldwide (including >15 million in the US) exposed. HAP from coal use is a human lung carcinogen, yet the epidemiological evidence on carcinogenicity of HAP from biomass use, primarily wood, is not conclusive. To robustly assess biomass’s carcinogenic potential, prospective studies of individuals experiencing a variety of HAP exposures are needed. We have built a global consortium of 13 prospective cohorts (HAPCO: Household Air Pollution Consortium) that have site- and disease-specific mortality and solid fuel use data, for a combined sample size of 587,257 participants and 57,483 deaths. HAPCO provides a novel opportunity to assess the association of HAP with lung cancer death while controlling for important confounders such as tobacco and outdoor air pollution exposures. HAPCO is also uniquely positioned to determine the risks associated with cancers other than lung as well as nonmalignant respiratory and cardiometabolic outcomes, for which prospective epidemiologic research is limited. HAPCO will facilitate research to address public health concerns associated with HAP-attributed exposures by enabling investigators to evaluate sex-specific and smoking status-specific effects under various exposure scenarios.

Background: Epidemiologic evidence on dietary carbohydrates and stroke risk remains controversial. Very few prospective cohort studies have been condu

Objectives To provide insight into the contributions of exposure measurements to job exposure matrices (JEMs), we examined the sensitivity of exposure-response associations between occupational benzene exposure and non-Hodgkin lymphoma (NHL) using benzene JEM-based estimates with and without measurement calibration. Methods NHL risk was examined in a prospective population-based cohort of 73,087 Shanghai women with no prevalent cancer at baseline and a valid occupational history. An ‘uncalibrated’ benzene JEM was developed using expert judgment to assign ordinal (0 to 3) probability and intensity ratings to each occupation and industry group. JEM intensity estimates were combined with >60,000 short-term, area benzene inspection measurements using a mixed-effects model framework that incorporated fixed effects for year and intensity rating and random effects for occupation, industry, and measurement occurrence. The model was used to derive ‘calibrated JEM’ estimates from the fixed effect model parameters and ‘job/industry-specific’ estimates from both the fixed effect model parameters and the best unbiased linear prediction estimates from the occupation and industry random effect terms. Cumulative exposure for each subject was calculated for each approach using varying exposure definition criteria based on 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 the calibrated and uncalibrated JEM estimates (Spearman correlation amongst exposed subjects: 0.64–0.87). The uncalibrated, calibrated, and job/industry-specific metrics all resulted in statistically significant exposure-response associations for NHL, with similar model fit. This similarity occurred because the measurement- and ordinal-based weights across the occupation intensity ratings were nearly identical in this study. Conclusions The measurement-based JEM estimates had similar model fit to the uncalibrated JEM estimates in this study; however, the measurement-based estimates allowed us to evaluate quantitative exposure-response curves.

Objective: To evaluate the association of uric acid (UA) levels with a panel of markers of oxidative stress and inflammation. Methods: Plasma UA levels, along with a panel of oxidative stress and inflammatory markers, were measured in 755 Chinese women. Results: Plasma UA levels were inversely associated with urinary levels of the oxidative stress marker F₂-isoprostanes and positively correlated to levels of inflammatory markers, such as C-reactive protein and some proinflammatory cytokines (tumor necrosis factor-α and interleukin-6) in blood as well as prostaglandin E₂ metabolites in urine. Conclusions: Plasma UA levels correlate to oxidation and inflammation biomarkers in opposite directions in women.

Objectives Epidemiologic studies of occupational lead exposure have suggested increased risks of cancers of the brain, kidney, lung, meninges, and stomach; however, the totality of the evidence is inconsistent. To clarify whether lead is a carcinogen, we investigated the relationship between occupational lead exposure and risks of these five cancer sites in two prospective cohort studies in Shanghai, China. Method Annual job/industry-specific estimates of lead fume and lead dust exposure were derived from a statistical model that combined expert ratings of lead intensity with inspection measurements collected by the Shanghai Centre for Disease Control and Prevention. The job/industry estimates were applied to the lifetime work histories of subjects from the Shanghai Women’s Health Study (73 363 participants) and the Shanghai Men’s Health Study (61 379 participants) to estimate cumulative exposure to lead dust and lead fume. Cohort-specific relative hazard rate ratios (RRs) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression models and then pooled using a random effects meta-analysis model. Results We observed a statistically significant increased risk of meningioma among individuals with estimated occupational exposure to lead dust or fumes (RR=2.4, 95% CI:1.1–5.0), and in particular among those with an above-median cumulative exposure to dust or fumes (RR=3.1, 95% CI:1.3–7.4). We observed suggestive associations with lead exposure for cancers of the kidney (RR=1.4, 95% CI:0.9–2.3) and brain (RR=1.8, 95% CI:0.7–4.8), and null findings for cancers of the lung and stomach. Conclusions Our findings provide additional evidence that occupational lead exposure increases risk of meningioma.

Background: Leisure time exercise has been linked to lower circulating levels of inflammatory markers. Few studies have examined the association of nonexercise physical activity with markers of inflammation and oxidative stress. Methods: This cross-sectional analysis included 1005 Chinese women aged 40–70 years. Usual physical activity was assessed through in-person interviews using a validated physical activity questionnaire. Plasma proinflammatory cytokines and urinary F₂-isoprostanes were measured. Multivariable linear models were used to evaluate the association of inflammatory and oxidative stress markers with nonexercise physical activity and its major components. Results: Nonexercise physical activity accounted for 93.8% of overall physical activity energy expenditure. Levels of nonexercise physical activity were inversely associated with circulating concentrations of interleukin (IL)-6 (P_trend=0.004), IL-1β (P_trend=0.03) and tumor necrosis factor-alpha (TNF-α) (P_trend=0.01). Multivariable-adjusted concentrations of these cytokines were 28.2% for IL-6, 22.1% for IL-1β, and 15.9% for TNF-α lower in the highest quartile of nonexercise physical activity compared with the lowest quartile. Similar inverse associations were found for two major components of nonexercise physical activity, walking and biking for transportation, and household activity. No significant associations were observed between nonexercise physical activity and oxidative stress markers. Conclusion: Daily nonexercise physical activity is associated with lower levels of systemic inflammation. This finding may have important public health implications because this type of activity is the main contributor to overall physical activity among middle-aged and elderly women.

Associations between polycyclic aromatic hydrocarbons (PAHs) and colorectal cancer have been reported previously but few studies have characterized PAH exposure using biological measurements. We evaluated colorectal cancer risk in relation to urinary concentration of 1-hydroxypyrene glucuronide (1-OHPG), a polycyclic aromatic hydrocarbon (PAH) metabolite, and assessed determinants of PAH exposure among controls in the Shanghai Women’s Health Study (SWHS). Concentrations of 1-OHPG were measured in spot urine samples collected from 343 colorectal cancer cases and 343 individually matched controls. Questionnaires were administered to collect information on demographic characteristics and reported exposures. Odds ratios were calculated for risk of colorectal cancer in relation to quartiles of urinary 1-OHPG concentration. Potential determinants of natural log-transformed urinary 1-OHPG concentration were evaluated among a combined sample of controls from this study and another nested case–control study in the SWHS (Ntotal=652). No statistically significant differences in risk of colorectal cancer by urinary 1-OHPG levels were observed. Among controls, the median (interquartile range) urinary 1-OHPG concentration was 2.01 pmol/mL (0.95-4.09). Active and passive smoking, using coal as a cooking fuel, eating foods that were cooked well done, and recent consumption of fried dough (e.g., yóutiáo) were associated with elevated levels of 1-OHPG, though only active smoking and fried dough consumption achieved statistical significance in multivariate analyses. This study does not provide evidence of an association between urinary levels of 1-OHPG and risk of colorectal cancer among women. Several environmental and dietary sources of PAH exposure were identified. Overall, the levels of 1-OHPG in this population of predominantly non-smoking women were considerably higher than levels typically observed among non-smokers in Europe, North America, and other developed regions.

Purpose: We recently reported an inverse association between soy food intake and lung cancer risk among nonsmoking women. The effect size for aggressive lung cancers was larger than that observed for other types of lung cancer. Therefore, we hypothesized that soy consumption may favorably affect the overall survival of patients with lung cancer. Patients and Methods: This analysis included 444 women with incident lung cancer identified from the Shanghai Women's Health Study. Prediagnosis soy food intake was assessed at enrollment and reassessed 2 years later. Proportional hazards models were used to evaluate the association between soy food intake and overall survival. Results: Of the 444 patients with lung cancer, 318 died during follow-up. Initial analyses including all patients showed that higher intake of soy food was associated with better overall survival after adjusting for demographic and lifestyle characteristics and other nonclinical factors. Larger effect sizes for the association were found after additional adjustment for tumor stage and treatment in analyses including 301 patients with data available on these clinical factors. Compared with the median intake of soy food, fully adjusted hazard ratios for total mortality associated with the 10th, 30th, 70th, and 90th percentiles of intake were 1.81 (95% CI, 1.26 to 2.59), 1.25 (95% CI, 1.09 to 1.42), 0.88 (95% CI, 0.80 to 0.97), and 0.89 (95% CI, 0.68 to 1.16), respectively. Similar inverse associations were observed for dietary isoflavone intake. Conclusion: This study suggests, to the best of our knowledge for the first time, that, among women with lung cancer, prediagnosis intake of soy food is associated with better overall survival.

The authors prospectively evaluated the association of soy food intake with lung cancer risk, overall and by tumor aggressiveness, and performed a meta-analysis of published data. Included in the analysis were 71,550 women recruited into the Shanghai Women's Health Study (Shanghai, China) in 1997–2000. Usual soy food intake was assessed at baseline and reassessed during follow-up through in-person interviews. During a mean follow-up period of 9.1 years, 370 incident lung cancer cases were identified; 340 patients were lifetime never smokers. After adjustment for potential confounders, soy food intake was inversely associated with subsequent risk of lung cancer (P_trend = 0.004); the hazard ratio for the highest quintile of intake compared with the lowest was 0.63 (95% confidence interval: 0.44, 0.90). This inverse association appeared predominately among women with later age at menopause (P_interaction = 0.01) and for aggressive lung cancer as defined by length of survival (P_{heterogeneity} = 0.057). Meta-analysis of 7 studies conducted among nonsmokers found a summary relative risk of 0.59 (95% confidence interval: 0.49, 0.71) for the highest categories of soy or isoflavone intake versus the lowest. This study suggests that soy food consumption may reduce lung cancer risk in nonsmoking women, particularly for aggressive tumors, and its effect may be modified by endogenous estrogens.