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_trend=0.05; Simpson: p_trend=0.04; Observed Species: p_trend=0.64). No case–control differences were apparent for beta diversity (p_MiRKAT=0.30). After accounting for multiple comparisons, a greater abundance of Spirochaetia (OR_low1.00 (reference), OR_medium0.61 (95% CI 0.32 to 1.18), OR_high0.42 (95% CI 0.21 to 0.85)) and Bacteroidetes (OR_low1.00 (reference), OR_medium0.66 (95% CI 0.35 to 1.25), OR_high0.31 (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_low1.00 (reference), OR_medium1.49 (95% CI 0.73 to 3.08), OR_high2.40 (95% CI 1.18 to 4.87)) and Lactobacillales order (OR_low1.00 (reference), OR_medium2.15 (95% CI 1.03 to 4.47), OR_high3.26 (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.

Household air pollution (HAP) from solid fuel combustion contributes to 2.6% of the global burden of disease. HAP emissions are an established lung carcinogen; however, associations with other cancer sites have not been fully explored. We conducted a meta-analysis of 18 case–control studies. Using fixed-effects models, utilizing the adjusted odds ratios (OR) and 95% confidence intervals (95% CI) from each study, we evaluated the association between HAP and cervical neoplasia (663 cases and 1747 controls) and upper aero-digestive tract cancers (6022 cases and 15 325 controls). We found that HAP was associated with cervical neoplasia (OR = 6.46; 95% CI = 3.12-13.36; 4 studies); oral (OR = 2.44; 95% CI = 1.87-3.19; 4 studies; 1000 cases/3450 controls); nasopharyngeal (OR = 1.80; 95% CI = 1.42-2.29; 6 studies; 2231 cases/2160 controls); pharyngeal (OR = 3.56; 95% CI = 2.22-5.70; 4 studies; 1036 cases/3746 controls); and laryngeal (OR = 2.35; 95% CI = 1.72- 3.21; 5 studies; 1416 cases/4514 controls) cancers. The elevated risk for esophageal cancer (OR = 1.92; 95% CI = 0.82-4.49; 2 studies; 339 cases/1455 controls) was non-significant. HAP was associated with cervical neoplasia among studies that accounted for HPV infection (OR = 9.60; 95% CI = 3.79-24.32) and smoking (OR = 4.72; 95% CI = 1.84-12.07). Similarly, our observed associations between HAP and upper aero-digestive tract cancers remained significantly elevated when analyses were restricted to studies that controlled for smoking. No significant publication bias was detected. Our results suggest that the carcinogenic effect of HAP observed for lung cancer may extend to other cancers, including those of the cervix and the upper aero-digestive tract. Further research is needed to confirm these associations in prospective studies.

Indoor gas stove use for cooking is associated with an increased risk of current asthma among children and is prevalent in 35% of households in the United States (US). The population-level implications of gas cooking are largely unrecognized. We quantified the population attributable fraction (PAF) for gas stove use and current childhood asthma in the US. Effect sizes previously reported by meta-analyses for current asthma (Odds Ratio = 1.34, 95% Confidence Interval (CI) = 1.12–1.57) were utilized in the PAF estimations. The proportion of children (<18 years old) exposed to gas stoves was obtained from the American Housing Survey for the US, and states with available data (n = 9). We found that 12.7% (95% CI = 6.3–19.3%) of current childhood asthma in the US is attributable to gas stove use. The proportion of childhood asthma that could be theoretically prevented if gas stove use was not present (e.g., state-specific PAFs) varied by state (Illinois = 21.1%; California = 20.1%; New York = 18.8%; Massachusetts = 15.4%; Pennsylvania = 13.5%). Our results quantify the US public health burden attributed to gas stove use and childhood asthma. Further research is needed to quantify the burden experienced at the county levels, as well as the impacts of implementing mitigation strategies through intervention studies.

This article presents the first detailed overview of the mechanisms that may underlie the relation of obesity with B-cell non-Hodgkin lymphomas (NHLs) and multiple myeloma (MM). Epidemiologic studies, including meta-analyses of prospective cohorts, have reported that the risks of NHL and MM are significantly increased in obese, relative to normal weight, women and men. Accumulating experimental and clinical evidence suggests that inflammatory cytokines, hyperinsulinemia, and sex hormones could play a role in the association of obesity with B-cell NHL and MM carcinogenesis. There is, however, a paucity of data published from appropriate large prospective cohort studies, and studies concurrently measuring these correlated factors, to formally determine the likely biologic factors driving the relationship of obesity with NHL and MM. Additional strengths and weaknesses of the current literature, as well as study design issues that need to be considered in conducting these studies, such as the exclusion of type 2 diabetics or postmenopausal women using hormone therapy, are discussed.