Association between combined exposure to ambient air pollutants, genetic risk, and incident gout risk: A prospective cohort study in the UK Biobank.

BACKGROUND: Limited research has been conducted on the association between long-term exposure to air pollutants and the incidence of gout. OBJECTIVES: This study aims to assess the individual and combined effects of prolonged exposure to five air pollutants (NO2, NOx, PM10, PMcoarse and PM2.52) on the incidence of gout among 458,884 initially gout-free participants enrolled in the UK Biobank. METHODS: Employing a land use regression model, we utilized an estimation method to ascertain the annual concentrations of the five air pollutants. Subsequently, we devised a weighted air pollution score to facilitate a comprehensive evaluation of exposure. The Cox proportional hazards model was utilized to investigate the association between ambient air pollution and gout risk. Interaction and stratification analyses were conducted to evaluate age, sex, BMI, and genetic predisposition as potential effect modifiers in the air pollution-gout relationship. Furthermore, mediation analyses were conducted to explore the potential involvement of biomarkers in mediating the association between air pollution and gout. RESULTS: Over a median follow-up time of 12.0 years, 7,927 cases of gout were diagnosed. Significant associations were observed between the risk of gout and a per IQR increase in NO2 (HR3: 1.05, 95 % CI4: 1.02-1.08, p = 0.003), NOx (HR: 1.04, 95 % CI: 1.01-1.06, p = 0.003), and PM2.5 (HR: 1.03, 95 % CI: 1.00-1.06, p = 0.030). Per IQR increase in the air pollution score was associated with an elevated risk of gout (p = 0.005). Stratified analysis revealed a significant correlation between the air pollution score and gout risk in participants ≥60 years (HR: 1.05, 95 % CI: 1.02-1.09, p = 0.005), but not in those <60 years (p = 0.793), indicating a significant interaction effect with age (p-interaction=0.009). Mediation analyses identified five serum biomarkers (SUA:15.87 %, VITD: 5.04 %, LDLD: 3.34 %, GGT: 1.90 %, AST: 1.56 %5) with potential mediation effects on this association. CONCLUSIONS: Long-term exposure to air pollutants, particularly among the elderly population, is associated with an increased risk of gout. The underlying mechanisms of these associations may involve the participation of five serum biomarkers.

Clinical characteristics and prognostic factors of male breast cancer in China.

Purpose: This study aimed to explore the clinical characteristics of male breast cancer (MBC) patients and the factors influencing their prognosis. Methods: We conducted a retrospective case series analysis of 117 MBC cases who were treated at Zhejiang Cancer Hospital from 2009 to 2022. Cox proportional hazard model was used to identify prognostic factors of MBC. Nomogram was constructed based on these factors, which was further evaluated by C-index and calibration curves. Results: A total of 115 MBC cases were finally included in our analyses, with median diagnosis age of 59 years. Of these cases, 80.0% were estrogen receptor (ER) positive, 79.2% were progesterone receptor (PR) positive, 48.7% were human epidermal growth factor receptor 2 (HER2) negative, and 42.6% had Ki67 levels higher than 15%. 108 (93.9%) cases underwent radical mastectomy, while only 3 (2.6%) received breast-conserving surgery. The Logrank test suggested that lymphocyte-to-monocyte ratio (LMR) was negatively associated with both overall survival (OS) and disease-free survival (DFS) of MBC, while platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) were only positively associated with OS (all P-values < 0.05). Multivariate regression analysis showed that age (HR 1.08, 95% CI 1.03-1.13) was significant prognostic factors for OS. Meanwhile, age (HR 1.06, 95% CI 1.02-1.10), histological differentiation grade (poorly differentiated/undifferentiated vs. well-differentiated: HR 2.55, 95% CI 1.05-6.17), and TNM stage (IV vs. I: HR 31.59, 95% CI 6.01-165.93) were also significant prognostic factors for DFS. Nomograms were developed for DFS, with C-indexes of 0.782, indicating good predictive performance. Conclusion: Increased age, bigger tumor size, higher TNM stage, and lower histological differentiation grade were associated with poor MBC prognosis, and LMR, PLR, and NLR might be potential predictors for MBC prognosis.

Air pollutants, genetic susceptibility, and the risk of incident gastrointestinal diseases: A large prospective cohort study.

A comprehensive overview of the associations between air pollution and the risk of gastrointestinal (GI) diseases has been lacking. We aimed to examine the relationships of long-term exposure to ambient particulate matter (PM) with aerodynamic diameter ≤2.5 µm (PM2.5), 2.5-10 µm (PMcoarse), ≤10 µm (PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx), with the risk of incident GI diseases, and to explore the interplay between air pollution and genetic susceptibility. A total of 465,703 participants free of GI diseases in the UK Biobank were included at baseline. Land use regression models were employed to calculate the residential air pollutants concentrations. Cox proportional hazard models were used to evaluate the associations of air pollutants with the risk of GI diseases. The dose-response relationships of air pollutants with the risk of GI diseases were evaluated by restricted cubic spline curves. We found that long-term exposure to ambient air pollutants was positively associated with the risk of peptic ulcer (PM2.5 : Q4 vs. Q1: hazard ratio (HR) 1.272, 95% confidence interval (CI) 1.179-1.372, NO2: 1.220, 1.131-1.316, and NOx: 1.277, 1.184-1.376) and chronic gastritis (PM2.5: 1.454, 1.309-1.616, PM10 : 1.232, 1.112-1.366, NO2: 1.456, 1.311-1.617, and NOx: 1.419, 1.280-1.574) after Bonferroni correction. Participants with high genetic risk and high air pollution exposure had the highest risk of peptic ulcer, compared to those with low genetic risk and low air pollution exposure (PM2.5: HR 1.558, 95%CI 1.384-1.754, NO2: 1.762, 1.395-2.227, and NOx: 1.575, 1.403-1.769). However, no significant additive or multiplicative interaction between air pollution and genetic risk was found. In conclusion, long-term exposure to ambient air pollutants was associated with increased risk of peptic ulcer and chronic gastritis.