A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development¹. Here we propose that environmental particulate matter measuring ≤2.5 μm (PM_2.5), known to be associated with lung cancer risk, promotes lung cancer by acting on cells that harbour pre-existing oncogenic mutations in healthy lung tissue. Focusing on EGFR-driven lung cancer, which is more common in never-smokers or light smokers, we found a significant association between PM_2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in four within-country cohorts. Functional mouse models revealed that air pollutants cause an influx of macrophages into the lung and release of interleukin-1β. This process results in a progenitor-like cell state within EGFR mutant lung alveolar type II epithelial cells that fuels tumorigenesis. Ultradeep mutational profiling of histologically normal lung tissue from 295 individuals across 3 clinical cohorts revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively. These findings collectively support a tumour-promoting role for PM_2.5 air pollutants and provide impetus for public health policy initiatives to address air pollution to reduce disease burden.

The Chang Gung Research Database (CGRD) is a de-identified database derived from original medical records of Chang Gung Memorial Hospital (CGMH), which comprises seven medical institutes located from the northeast to southern regions of Taiwan. The volume of medical services performed in CGMH is large, and clinical and scientific studies based on the CGRD are reported to be of high quality. However, the CGRD as a useful database for research has not been analyzed before. The objective of the study was to analyze the CGRD with regard to its characteristics and coverage of Taiwan's population. We performed a nationwide cohort study using population-based data from the Taiwan National Health Insurance Research Database (NHIRD). All patients who had any medical record of outpatient visits or admission between January 1, 1997, and December 31, 2010, were included, and the sex ratio, age distribution, socioeconomic status, urbanicity, severity of illness, prevalence of specific disease, and coverage of the CGRD were analyzed. The sex ratio, age distribution, socioeconomic status, and urbanicity of the population of the CGRD are different from those of Taiwan NHIRD and medical centers in Taiwan (all the pairwise p < 0.05). The severity of comorbidities, and prevalence of specific diseases of the population of the CGRD are significantly higher than those of Taiwan NHIRD and medical centers in Taiwan for both outpatient and inpatient samples (all the pairwise p < 0.05). The overall coverage of the CGRD was 21.2% for outpatients and 12.4% for inpatients. The disease-specific coverage of the CGRD was 27-34% for outpatients and 14-21% for inpatients. The CGRD is a multi-institutional, original medical record-based research database with high overall and disease-specific coverage of Taiwan. The population of the CGRD has significantly higher severity of comorbidities, and prevalence of specific diseases than those of Taiwan NHIRD and medical centers in Taiwan.

Purpose: Statins may have protective effects against cancer, but no studies have focused on their effects in patients with chronic hepatitis C virus (HCV) infection. The purpose of this study was to investigate the association between use of statins and risk of hepatocellular carcinoma (HCC) in HCV-infected patients. Patients and Methods: Ours was a population-based cohort study of 260,864 HCV-infected patients enrolled in the Taiwan National Health Insurance Research Database since January 1, 1999, and observed through December 31, 2010. Cox proportional hazards regression with time-dependent covariates for drug exposures was employed to evaluate the association between statin use and HCC risk. Results: There were 27,883 cases of HCC in the HCV cohort during a follow-up period of 2,792,016.6 person-years. Among the 35,023 patients using statins (defined as ≥ 28 cumulative defined daily doses [cDDDs]), 1,378 had HCC. Among the 225,841 patients not using statins (< 28 cDDDs), 26,505 were diagnosed with HCC. A dose-response relationship between statin use and HCC risk was observed. The adjusted hazard ratios were 0.66 (95% CI, 0.59 to 0.74), 0.47 (95% CI, 0.40 to 0.56), and 0.33 (95% CI, 0.25 to 0.42) for patients with 28 to 89, 90 to 180, and > 180 cDDDs per year, respectively, relative to nonusers. The reduction in risk also demonstrated a progressive duration-response relationship in patients with ≥ 28 cDDDs per year when compared with nonusers. Conclusion: Among patients with HCV infection, statin use was associated with reduced risk of HCC. Further research is needed to elucidate the mechanism responsible for this effect.

Limited studies have prospectively examined the role of body mass index (BMI) as a major risk factor for asthma during adolescence. This study investigates whether BMI is associated with increased risk of developing physician-diagnosed asthma during 12-month follow-up among adolescents with undiagnosed asthma-like symptoms at baseline.