Rationale: Both genetic and environmental factors contribute to lung cancer, but the degree to which air pollution modifies the impact of genetic susceptibility on lung cancer remains unknown. Objectives: To investigate whether air pollution and genetic factors jointly contribute to incident lung cancer. Methods: We analyzed data from 455,974 participants (53% women) without previous cancer at baseline in the UK Biobank. The concentrations of particulate matter (PM_2.5, PM_coarse and PM₁₀), nitrogen dioxide (NO₂), and nitrogen oxides (NO_x) were estimated by land-use regression models, and the association between air pollutants and incident lung cancer was investigated using a Cox proportional hazard model. Furthermore, we constructed a polygenic risk score and evaluated whether air pollutants modified the effect of genetic susceptibility on the development of lung cancer. Measurements and Main Results: The results showed significant associations between the risk of lung cancer and PM_2.5 (hazard ratio [HR]: 1.63, 95% confidence interval [CI]: 1.33-2.01; per 5 μg/m³), PM₁₀ (1.53, 1.20-1.96; per 10 μg/m³), NO₂ (1.10, 1.05-1.15; per 10 μg/m³), and NO_x (1.13, 1.07-1.18; per 20 μg/m³). There were additive interactions between air pollutants and the genetic risk. Compared with participants with low genetic risk and low air pollution, those with high air pollution and high genetic risk had the highest risk of lung cancer (PM_2.5: HR: 1.71, 95% CI:1.45-2.02; PM₁₀: 1.77, 1.50-2.10; NO₂: 1.77, 1.42-2.22; NO_x: 1.67, 1.43-1.95). Conclusion: Long-term exposure to air pollution may increase the risk of lung cancer, especially in those with high genetic risk.

Aims: To construct a polygenic risk score (PRS) for coronary artery disease (CAD) and comprehensively evaluate its potential in clinical utility for primary prevention in Chinese populations. Methods and results: Using meta-analytic approach and large genome-wide association results for CAD and CAD-related traits in East Asians, a PRS comprising 540 genetic variants was developed in a training set of 2800 patients with CAD and 2055 controls, and was further assessed for risk stratification for CAD integrating with the guideline-recommended clinical risk score in large prospective cohorts comprising 41 271 individuals. During a mean follow-up of 13.0 years, 1303 incident CAD cases were identified. Individuals with high PRS (the highest 20%) had about three-fold higher risk of CAD than the lowest 20% (hazard ratio 2.91, 95% confidence interval 2.43–3.49), with the lifetime risk of 15.9 and 5.8%, respectively. The addition of PRS to the clinical risk score yielded a modest yet significant improvement in C-statistic (1%) and net reclassification improvement (3.5%). We observed significant gradients in both 10-year and lifetime risk of CAD according to the PRS within each clinical risk strata. Particularly, when integrating high PRS, intermediate clinical risk individuals with uncertain clinical decision for intervention would reach the risk levels (10-year of 4.6 vs. 4.8%, lifetime of 17.9 vs. 16.6%) of high clinical risk individuals with intermediate (20–80%) PRS. Conclusion: The PRS could stratify individuals into different trajectories of CAD risk, and further refine risk stratification for CAD within each clinical risk strata, demonstrating a great potential to identify high-risk individuals for targeted intervention in clinical utility.

Human papillomavirus (HPV) is one of the most prevalent sexually transmitted viruses. Despite the increasing evidence of HPV prevalence in semen, the worldwide distribution of HPV types in semen and risk for male infertility remain inconclusive. Four electronic databases were searched for English language studies conducted between January 1990 and December 2016 that reported HPV DNA prevalence in semen. Based on the PRISMA guidelines, HPV prevalence was estimated among general population and fertility clinic attendees, respectively, and heterogeneity testing was performed using Cochran’s Q and I 2 statistics. The association between HPV positivity and male infertility was evaluated by a meta-analysis of case-control studies. A total of 31 eligible studies comprising 5194 males were included. The overall prevalence of HPV DNA in semen was 11.4% (95% CI = 7.8-15.0%) in general population (n = 2122) and 20.4% (95% CI = 16.2-24.6%) in fertility clinic attendees (n = 3072). High-risk type prevalence was 10.0% (95% CI = 5.9-14.0%) and 15.5% (95% CI = 11.4-19.7%), respectively. HPV16 was the most common type, with a prevalence of 4.8% (95% CI = 1.7-7.8%) in general population and 6.0% (95% CI = 3.8-8.2%) in fertility clinic attendees. A significantly increased risk of infertility was found for males with HPV positivity in semen (OR = 2.93, 95% CI = 2.03-4.24). Seminal HPV infection is common worldwide, which may contribute to the risk of male infertility.

Epidemiological evidence remains conflicting regarding diet and risk of lung cancer. We sought to systematically investigate whether dietary factors are associated with the risk of incident lung cancer in the UK Biobank. A total of 416,588 participants (54% women) from the UK Biobank were included in the present study. Based on baseline data from FFQs, 3 main dietary patterns were identified by using principal component analysis. Cox proportional hazards models were used to investigate the association of individual food groups and dietary patterns with lung cancer risk. During a median follow-up of 7.13 y, 1782 incident lung cancer cases were documented. The association analysis showed high intake of red meat and processed meat was associated with an increased risk of lung cancer (HR_{per 50 g/d}: 1.36; 95% CI: 1.13, 1.65 for red meat; HR_{per 25 g/d}: 1.30; 95% CI: 1.10, 1.53 for processed meat). However, the consumption of fruits (HR_{per 100 g/d}: 0.90; 95% CI: 0.84, 0.95), vegetables (HR_{per 100 g/d}: 0.89; 95% CI: 0.81, 0.99), breakfast cereals (HR_{per 50 g/d}: 0.81; 95% CI: 0.74, 0.89), and dietary fiber (HR_{per 5 g/d}: 0.76; 95% CI: 0.69, 0.84) was inversely associated with the risk of lung cancer. For the dietary pattern analysis [quartile (Q) comparison], high adherence to the Prudent pattern (HR_{Q4 compared with Q1}: 0.84; 95% CI: 0.73, 0.96) was associated with a lower risk of lung cancer, whereas the Western pattern (HR_{Q4 compared with Q1}: 1.27; 95% CI: 1.11, 1.46) was associated with a higher risk of lung cancer. Our study indicated that a diet characterized by high intake of fruits, vegetables, breakfast cereals, and dietary fiber, as well as low intake of red meat and processed meat, was associated with a lower risk of lung cancer.

Context: Although an inverse association between vitamin D status and mortality has been reported in observational studies, the precise association shape and optimal vitamin D status remain undetermined. Objective: To investigate the association between vitamin D status and risk of all-cause and cause-specific mortality and estimate optimal serum 25-hydroxyvitamin D [25(OH)D] concentrations. Design: Prospective cohort study. Setting: UK Biobank. Participants: 365 530 participants who had serum 25(OH)D measurements and no history of cardiovascular disease (CVD), cancer, or diabetes at baseline (2006-2010). Main outcome measures: All-cause and cause-specific mortality. Results: During a median follow-up of 8.9 (interquartile range: 8.3-9.5) years, 10 175 deaths occurred, including 1841 (18.1%) due to CVD and 5737 (56.4%) due to cancer. The multivariate analyses revealed nonlinear inverse associations, with a decrease in mortality risk appearing to level off at 60 nmol/L of 25(OH)D for all-cause and CVD deaths and at 45 nmol/L for cancer deaths. Compared to participants with 25(OH)D concentrations below the cutoffs, those with higher concentrations had a 17% lower risk for all-cause mortality (hazard ratio [HR]: 0.83, 95% confidence interval [CI]: 0.79-0.86), 23% lower risk for CVD mortality (HR: 0.77, 95% CI: 0.68-0.86), and 11% lower risk for cancer mortality (HR: 0.89, 95% CI: 0.84-0.95). Conclusions: Higher 25(OH)D concentrations are nonlinearly associated with lower risk of all-cause, CVD, and cancer mortality. The thresholds of 45 to 60 nmol/L might represent an intervention target to reduce the overall risk of premature death, which needs further confirmation in large clinical trials.

To prospectively investigate the association between sleep traits and lung cancer risk, accounting for the interactions with genetic predisposition of lung cancer. We included 469 691 individuals free of lung cancer at recruitment from UK Biobank, measuring sleep behaviors with a standardized questionnaire and identifying incident lung cancer cases through linkage to national cancer and death registries. We estimated multivariable-adjusted hazard ratios (HRs) for lung cancer (2177 incident cases) across four sleep traits (sleep duration, chronotype, insomnia, and snoring) and examined the interaction and joint effects with a lung cancer polygenic risk score. A U-shaped association was observed for sleep duration and lung cancer risk, with an 18% higher risk (95% confidence interval [CI]: 1.07 to 1.30) for short sleepers and a 17% higher risk (95% CI: 1.02 to 1.34) for long sleepers compared with normal sleepers (7–8 h/day). Evening preference was associated with elevated lung cancer risk compared with morning preference (HR: 1.25; 95% CI: 1.07 to 1.46), but no association was found for insomnia or snoring. Compared with participants with favorable sleep traits and low genetic risk, those with both unfavorable sleep duration (8 hours) or evening preference and high genetic risk showed the greatest lung cancer risk (HR_{sleep duration}: 1.83; 95% CI: 1.47 to 2.27; HR_chronotype: 1.85; 95% CI: 1.34 to 2.56). Both unfavorable sleep duration and evening chronotype were associated with increased lung cancer incidence, especially for those with low to moderate genetic risk. These results indicate that sleep behaviors as modifiable risk factors may have potential implications for lung cancer risk.