Arsenic, tobacco use, and lung cancer: An occupational cohort with 27 follow-up years.

BACKGROUND: We explored the shape of the exposure-response relationship of arsenic-related lung cancer and the interaction between arsenic and tobacco use. METHODS: A total of 3278 tin miners with at least 10 years of arsenic exposure were enrolled since 1992 and followed up for 27 years. After excluding radon-exposed miners and former smokers, 1620 miners were included into the sub-cohort. Lung cancer risks were estimated by modeling total exposure and intensity of arsenic exposure. RESULTS: The cohort experienced 73,866 person-years and 414 lung cancer cases. Firstly, the ERR/mg/m3-year was 0.0033 (95% CI: 0.0014-0.0045) in arsenic concentration <3 mg/m3 and 0.0056 (95% CI: 0.0035-0.0073) in arsenic concentration ≥3 mg/m3. After adjusting for cumulative arsenic exposure, and the ERR/mg/m3 increased with increasing intensity (0.129 (95% CI: 0.039, 0.189)). Secondly, an unique aspect of this population was the early age at first arsenic exposure for workers. Results showed that lung cancer incidence risk from exposed in childhood (<13 years) was non-significantly greater than those in other age groups (13-17 and ≥ 18 years). Finally, the most likely joint effects of inhaled arsenic and tobacco use was sub-multiplicative. CONCLUSION: This study enlightened us that for fixed cumulative arsenic exposure, higher concentration over shorter duration might be more deleterious than lower concentration over longer duration. Substantial reductions in the lung cancer burden of smokers exposed to arsenic could be achieved by reductions in either exposure.

Quantitative evaluation of radon, tobacco use and lung cancer association in an occupational cohort with 27 follow-up years.

BACKGROUND: Occupational radon cohorts provide important information about exposure at residential level, which are difficult to observe prospectively. However, evidence about radon-related lung cancer risks from initial exposure in childhood or interaction between radon and smoking is still limited. METHODS: A total of 6017 tin miners with at least 10 years of underground radon exposure were enrolled beginning in 1992 and followed for up to 27 years. Lung cancer risks were estimated by modeling total and intensity of radon exposure. RESULTS: A total of 933 lung cancer cases occurred in this cohort over 89,092 person-years of follow up. Excess relative risk increased by 0.96% per cumulative working level month (WLM). A unique aspect of this population was the early age at first radon exposure for workers. Results showed that lung cancer risk from initial radon exposure in childhood (<13 years old) was greater than risk when first exposure occurred at later ages (13-17, 18-24, and ≥ 25 years old). Moreover, risk declined with years since last exposure and attained age, but increased with age at last exposure. Importantly, these patterns were stable after adjustment for tobacco use or arsenic exposure. For joint effects of radon and other agents, our results support sub-multiplicative as the most likely model for interaction between radon and tobacco use or arsenic exposure. CONCLUSION: This study highlights the possible importance of radon exposure in childhood in cancer etiology and suggests another potential strategy to mitigate the global lung cancer burden.

Effect of Arsenic Exposure and Cigarette Smoking on Total and Cause-Specific Mortality: An Occupational Cohort With 27 Follow-up Years.

BACKGROUND: The relationship between arsenic exposure and all-cause mortality and the joint effects of arsenic exposure and smoking have been poorly described in previous studies. METHODS: After 27 years of follow-up, a total of 1738 miners were included in the analysis. Different statistical methods were used to explore the relationship between arsenic exposure and smoking and the risk of all-cause mortality and various causes of death. RESULTS: A total of 694 deaths occurred during the 36,199.79 person-years of follow-up. Cancer was the leading cause of death, and arsenic-exposed workers had significantly higher mortality rates for all-cause, cancer, and cerebrovascular disease. All-cause, cancer, cerebrovascular disease, and respiratory disease increased with cumulative arsenic exposure. CONCLUSIONS: We demonstrated the negative effects of smoking and arsenic exposure on all-cause mortality. More effective actions should be taken to reduce arsenic exposure in miners.

The impact of low-dose CT on smoking behavior among non-smokers, former-smokers, and smokers: A population-based screening cohort in rural China.

BACKGROUND: Lung cancer screening may provide a "teachable moment" for the smoking cessation and relapse prevention. However, the impact of lung cancer screening on smoking initiation in non-smokers has not been reported. METHODS: A baseline smoking behavior survey was conducted in 2000 participants who were screened by low-dose computed tomography (LDCT) from 2014 to 2018. All participants were re-surveyed on their smoking behavior in 2019. Of these, 312 participants were excluded, leaving 1688 participants in the final analysis. The smoking initiation rate in baseline non-smokers, the relapse rate in baseline former smokers, and the abstinence rate in baseline current smokers were calculated, respectively. The associations between screening results, demographic characteristics, and smoking behavior change were analyzed using multivariable logistic regression. RESULTS: From 2014 to 2019, smoking prevalence significantly decreased from 52.6% to 49.1%. The prevalence of smoking initiation, relapse, and abstinence in baseline non-smokers, former, and current smokers was 16.8%, 22.9%, and 23.7%, respectively. The risk of smoking initiation in baseline non-smokers was significantly higher in those with negative screening result (adjusted OR = 2.97, 95% CI: 1.27-6.94). Compared to smokers who only received baseline screening, the chance of smoking abstinence in baseline current smokers was reduced by over 80% in those who attended 5 rounds of screening (adjusted OR = 0.15, 95% CI:0.08-0.27). No significant associations were found between smoking relapse and prior screening frequency, with at least one positive screening result. Age, gender, occupational exposure, income, and smoking pack years were also associated with smoking behavior changes. CONCLUSIONS: The overall decreased smoking prevalence indicated an overwhelming effect of "teachable moment" on "license to smoke." A tailored smoking cessation strategy should be integrated into lung cancer screening.

Effect of Time Since Smoking Cessation on Lung Cancer Incidence: An Occupational Cohort With 27 Follow-Up Years.

Background: This special cohort reveals the effect of smoking cessation in occupational miners exposed to radon and arsenic. Methods: A total of 9,134 tin miners with at least 10 years of underground radon and arsenic exposure were enrolled beginning in 1992 and followed for up to 27 years. Detailed smoking information was collected at baseline, and information on smoking status was consecutively collected from 1992 to 1996. The Cox proportional hazards model was used to explore the relationship between time since smoking cessation and lung cancer. Results: A total of 1,324 lung cancer cases occurred in this cohort over 167,776 person-years of follow-up. Among populations exposed to radon and arsenic, miners after quitting smoking for 10 years or more had almost halved their lung cancer risk [adjusted hazard ratio (HR) = 0.55, 95% CI: 0.38-0.79], compared with current smokers. Among miners after quitting smoking for 5 years or more, lung cancer incidence approximately halved (HR = 0.52, 95% CI: 0.30-0.92) for squamous cell lung carcinoma, while it showed no significant decline for adenocarcinoma (HR = 0.79, 95% CI: 0.34-1.85). Conclusion: Smoking cessation for 10 years or more halved lung cancer incidence among miners exposed to radon and arsenic, and the benefit was more pronounced among squamous cell lung carcinoma.

Synergy of arsenic with smoking in causing cardiovascular disease mortality: A cohort study with 27 follow-up years in China.

Background: To explore the patterns of the exposure-response relationship between arsenic exposure and cardiovascular disease (CVD) mortality and investigate the effect of cigarette smoking on the association. Methods: Seven thousand seven hundred thirty-five tin miners with at least 10 years of arsenic exposure were enrolled since 1992 and followed up for 27 years. Each individual's air arsenic exposure at workplace was calculated by time weighted average arsenic concentration × exposure months. Detailed information on smoking was collected at baseline, and information on smoking status was collected for five consecutive years from 1992 to 1996. Hazard ratio (HR) and 95% confidence interval (CI) for the risk of CVD were estimated using Cox proportional hazards models. Results: A total of 1,046 CVD deaths occurred in this cohort over 142,287.7 person-years of follow up. We firstly reported that for equal cumulative exposure, participants exposed to higher concentrations over shorter duration had a higher risk of CVD mortality than those exposed to lower concentration over longer duration. The HR and 95% CI were 1.38 (95%CI: 1.03-1.85) in participants exposed to arsenic concentration (45.5-99.5 mg/m3), 1.29 (95%CI: 1.02-1.67) in 99.5-361.0 mg/m3. Further, participants with age at first exposure <18 years had a significantly higher risk of morality from CVD, cerebrovascular and heart diseases than those with ≥18 years. Finally, all synergy indices were greater than 1 (range, 1.11-2.39), indicating that the joint effect of arsenic exposure and cigarette smoking on CVD mortality was greater than the sum of their individual effect. Conclusions: Exposure to air arsenic at workplace is adversely associated with mortality from CVD, especially among smokers younger than 18 years and smokers.

[Analysis of sensitivity and specificity of sputum cytology screening for lung cancer with different positive criteria].

OBJECTIVE: To discuss the effect of different positive criteria on the sensitivity and specificity of sputum cytology screening for lung cancer among Yunnan tin miners. METHODS: 9223 Yunnan tin miners who received at least one annual sputum cytology screening for lung cancer during the period between 1992 and 1999 were recruited in the study. At time of enrollment, all participants were aged over 40 years old, had at least 10 years of employment as an underground miner and(or) smelter, and had not been diagnosed with malignancy. In our study, a true positive was categorized as having at least one prior positive sputum screening and a diagnosis of lung cancer, while a true negative, by our definition, signified negative sputum examinations and no diagnosis of lung cancer during the follow up time. Based on different positive criteria, sensitivity and specificity of sputum cytology were computed and receiver operating characteristic (ROC) curve analysis was conducted. Z statistic was used to test the differences of the area under ROC based on Hanley and McNeil method. RESULTS: By the end of following up on December 31, 2001, a total 500 lung cancer cases were diagnosed among 9223 participants: most were squamous cell carcinoma (55.8% (222/398)) and central lung cancers (68.5% (316/461)). 150 lung cancer cases had a previous positive sputum screening result. When positive criteria were taken as grave atypical metaplasia, moderate atypical metaplasia and slight atypical metaplasia, the corresponding sensitivities were 30.0% (150/500), 36.4% (182/500), 53.0% (265/500) respectively; while the corresponding specificities were 98.9% (8628/8723), 95.1% (8611/8723), 77.9% (7033/8723) respectively. The areas under ROC curve according to different positive criterias were 0.645 (95%CI: 0.635 - 0.654), 0.657 (95%CI: 0.668 - 0.667), 0.655 (95%CI: 0.645 - 0.664) respectively. There were no significant differences found in the comparisons between grave and moderate atypical metaplasia, grave and slight atypical metaplasia, moderate and slight atypical metaplasia(Z statistics were 0.780, 0.645, 0.209 respectively, all P values > 0.05). CONCLUSION: While the standard of positive criteria for diagnosis of lung cancer decreased, the sensitivity of sputum cytology screening increased and the specificity decreased. Since there were no significant differences of accuracy for different positive criteria.

Performance of lung cancer screening with low-dose CT in Gejiu, Yunnan: A population-based, screening cohort study.

BACKGROUND: The performance of lung cancer screening with low-dose computed tomography (CT) (LDCT) in China is uncertain. This study aimed to evaluate the performance of LDCT lung cancer screening in the Chinese setting. METHODS: In 2014, a screening cohort of lung cancer with LDCT was established in Gejiu, Yunnan Province, a screening center of the Lung Cancer Screening Program in Rural China (LungSPRC). Participants received a baseline screening and four rounds of annual screening with LDCT in two local hospitals until June 2019. We analyzed the rates of participation, detection, early detection, and the clinical characteristics of lung cancer. RESULTS: A total of 2006 participants had complete baseline screening results with a compliance rate of 98.4%. Of these, 1411 were high-risk and 558 were nonhigh-risk participants. During this period, 40 lung cancer cases were confirmed, of these, 35 were screen-detected, four were post-screening and one was an interval case. The positive rate of baseline and annual screening was 9.7% and 9.0%, while the lung cancer detection rate was 0.4% and 0.6%, respectively. The proportion of early lung cancer increased from 37.5% in T0 to 75.0% in T4. Adenocarcinoma was the most common histological subtype. Lung cancer incidence according to the criteria of LungSPRC and National Lung Cancer Screening Trial (NLST) was 513.31 and 877.41 per 100 000 person-years, respectively. CONCLUSIONS: The program of lung cancer screening with LDCT showed a successful performance in Gejiu, Yunnan. However, further studies are warranted to refine a high-risk population who will benefit most from LDCT screening and reduce the high false positive results. KEY POINTS: This study reports the results of lung cancer screening with LDCT in Gejiu, Yunnan, a high-risk area of lung cancer, and it demonstrates that lung cancer screening with LDCT is effective in detecting early-stage lung cancer. Our program provides an opportunity to explore the performance of LDCT lung cancer screening in the Chinese context.

China national lung cancer screening guideline with low-dose computed tomography (2015 version).

BACKGROUND: Lung cancer is the leading cause of cancer-related death in China. Results from a randomized controlled trial using annual low-dose computed tomography (LDCT) in specific high-risk groups demonstrated a 20% reduction in lung cancer mortality. METHODS: A China national lung cancer screening guideline was developed by lung cancer early detection and treatment expert group appointed by the National Health and Family Planning Commission, based on results of the National Lung Screening Trial, systematic review of evidence related to LDCT screening, and protocol of lung cancer screening program conducted in rural China. RESULTS: Annual lung cancer screening with LDCT is recommended for high risk individuals aged 50-74 years who have at least a 20 pack-year smoking history and who currently smoke or have quit within the past five years. Individualized decision making should be conducted before LDCT screening. LDCT screening also represents an opportunity to educate patients as to the health risks of smoking; thus, education should be integrated into the screening process in order to assist smoking cessation. CONCLUSIONS: A lung cancer screening guideline is provided for the high-risk population in China.

Prior lung disease and lung cancer risk in an occupational-based cohort in Yunnan, China.

We used the data from a prospective cohort study among tin miners in Yunnan, China to investigate whether prior lung disease is a risk factor for lung cancer. Information on prior lung disease was obtained from baseline questionnaires. The Cox proportional hazards model was used to examine the relationship between prior lung disease and lung cancer risk. From 1992 to 2001, a total of 502 lung cancer cases were confirmed among 9295 cohort participants. Prior chronic bronchitis was associated with an increase in lung cancer risk with an adjusted HR of 1.50 (95% CI: 1.24-1.81). There was an increased risk of developing squamous cell carcinoma in the setting of prior chronic bronchitis and small cell carcinoma in association with asthma with an adjusted HRs of 1.57 (95% CI: 1.19-2.09) and 2.56 (95% CI: 1.38-4.75), respectively. This prospective study provides further evidence that prior chronic bronchitis correlates with increased lung cancer risk, especially for squamous cell carcinoma. Asthma is associated with increased risk of small cell lung carcinoma.

Attributable causes of lung cancer incidence and mortality in China.

The aims of our study were to estimate the contribution of known lung cancer risk factors, and provide evidence to support the National Cancer Prevention and Control Program in China. We calculated the proportion of lung cancer attributable to specific risk factors. Data on exposure prevalence were from meta-analyses and large-scale national surveys of representative samples of the Chinese population. Data on relative risks were from meta-analyses and large-scale prospective studies. Lung cancer mortality and incidence were taken from the Third National Death Survey and from cancer registries in China. We estimated that in China 285 304 lung cancer deaths and 327 465 cases were attributable to smoking, involuntary smoking (women only), occupational exposure, indoor radon, and low fruit intake in 2005. The proportion of lung cancer deaths attributable to smoking, involuntary smoking among non-smoking women, occupational exposure, indoor radon and low fruit intake was 56.9%, 11.1%, 9.5%, 0.2% and 12.4%, respectively. About 41% of lung cancer mortality and incidence in women was caused by risk factors in our study. However, over half of lung cancer deaths and cases among women were not attributable to known risk factors. It is necessary to conduct large-scale studies to identify additional risk factors of lung cancer in non-smoking women.

Association between sputum atypia and lung cancer risk in an occupational cohort in Yunnan, China.

BACKGROUND: Individuals with cytologic atypia in sputum may be at high risk for the development of lung cancer. METHODS: A prospective cohort study was conducted among occupational tin miners in Yunnan, China, based on an annual lung cancer screening program. Sputum samples were collected prospectively at baseline and the following seven annual screenings. The associations between risk factors and sputum cytology were analyzed by univariate and multivariate logistic regression. A proportional hazard model was used to analyze the association between the baseline sputum results and the incidence of lung cancer. The effect of consecutive sputum cytology on the increase of lung cancer risk was analyzed by logistic regression. RESULTS: Sputum cytologic atypia was associated with age, smoking, occupational radon and arsenic exposure, and asthma. Sputum cytologic atypia was an independent risk factor for lung cancer with an adjusted hazard ratio (HR) of 3.82 (95% confidence interval [CI], 2.82 to 5.18) in comparing normal to moderate or worse atypia. Compared to the lung cancer risk associated with normal sputum, the risk was significantly higher according to the degree of atypia for squamous carcinomas, small cell lung cancer and central lung cancer, with adjusted HRs of 5.70 (95% CI, 3.78 to 8.59), 3.32 (95% CI, 1.31 to 8.45), and 4.93 (95% CI, 3.51 to 6.92), respectively. CONCLUSIONS: Sputum atypia is associated with an increased risk of lung cancer. Sputum cytologic examination combined with other screening examinations may play an important role in the early detection of lung cancer or in the selection of the optimal target population for more intensive lung cancer screening among this occupational cohort or similar population.

Effect of environmental exposure to cadmium on pregnancy outcome and fetal growth: a study on healthy pregnant women in China.

The objective of the present study was to evaluate the potential effect of environmental exposure to cadmium on pregnancy outcome and fetal growth. Normal pregnant women were selected from Da-ye city of Hubei province, a cadmium-polluted area, from November 2002 through January 2003. Whole blood of pregnant women, cord blood, and placenta were collected and cadmium levels were determined by inductively coupled plasma emission mass spectroscopy. Incidence rate of preterm labor (gestational age < or = 37 weeks) and neonatal asphyxia, neonatal birth height, and birth weight were compared between lower and higher cadmium exposure level groups. Whole blood cadmium of 44 mothers ranged from 0.80 to 25.20 microg/L. Cadmium concentration in maternal blood was significantly higher than that in cord blood (t = 11.44, P < 0.01). Placenta cadmium ranged from 0.084 to 3.97 microg/g dry weight. After adjustment for maternal age, history of gestation, abortion and lactation, Logistic regression analysis showed that there was no significant association between cadmium exposure levels and pregnancy outcome (premature labor or neonatal asphyxia). Multiple linear regression analysis showed that, cord blood cadmium level, but not maternal blood cadmium and placenta cadmium, was significantly negatively associated with neonatal birth height (t= -2.33, P < 0.05). Compared with lower cord blood cadmium level (< or = 0.40 microg/L), higher level of cord blood cadmium (>0.40 microg/L) was associated with 2.24cm decrease in neonatal birth height. There was no significant association between cadmium exposure and birth weight. It was concluded that environmental exposure to cadmium significantly lower neonatal birth height.