Socioeconomic disparity in the natural history of cutaneous melanoma: evidence from two large prospective cohorts.

BACKGROUND: Previous studies on the associations between socioeconomic status (SES) and cutaneous malignant melanoma (CMM) failed to distinguish the effects of different SES factors under an individual-data-based prospective study design. METHODS: Based on UK Biobank (UKB) and China Kadoorie Biobank (CKB), we estimated the effects of four SES factors on transitions from baseline to CMM in situ, subsequently to invasive CMM and further CMM mortality by applying multistate models. We further explored to which extent the associations between SES and CMM incidence could be explained by potential mediators including sun exposure, lifestyle and ageing in UKB. RESULTS: In multistate analyses, good household income was independently associated with an increased risk of CMM in situ (HR=1.38, 95% CI: 1.21 to 1.58) and invasive CMM (HR=1.34, 95% CI: 1.22 to 1.48) in UKB. These findings were partly validated in CKB. Especially in UKB, we observed an increased risk of CMM in situ and invasive CMM among participants with good type of house; only good education was independently associated with lower risk of evolving to invasive CMM among patients with CMM in situ (HR=0.69, 95% CI: 0.52 to 0.92); only good household income was independently associated with lower risk of CMM mortality among patients with CMM (HR=0.65, 95% CI: 0.45 to 0.95). In mediation analysis, the proportions attributable to the mediating effect were <6% for all selected variables, including self-reported sun exposure-related factors. CONCLUSION: SES factors have different effects on the incidence and progression of CMM. The association between SES and incident CMM is neither causal nor well explained by selected mediators.

Age at Natural Menopause, Reproductive Lifespan, and the Risk of Late-Onset Psoriasis and Psoriatic Arthritis in Women: A Prospective Cohort Study.

Although a peak incidence of psoriasis in women aged around 60 years has been observed, the link between reproductive lifespan and late-onset psoriatic diseases is underexplored. This study aims to elucidate the association between reproductive lifespan and the risk of late-onset psoriasis and psoriatic arthritis (PsA). Utilizing the UK Biobank data, we conducted a prospective cohort study in postmenopausal women without baseline psoriatic diseases. The exposure variables included age at natural menopause (ANM) and duration from menarche to menopause, termed reproductive years. The outcome variables were incident psoriasis and PsA. We employed Cox regression analysis, factoring in polygenic risk scores for psoriatic diseases and recognized risk factors. We found that later ANM and longer reproductive years were significantly associated with decreased risks of late-onset psoriasis and PsA in a dose-dependent manner (P<.05). ANM after age 55 years led to a 34 and 46% risk reduction in late-onset psoriasis and PsA, respectively, compared with ANM before age 45 years (P<.001). The population-attributable risks of ANM were 17.4% for late-onset psoriasis and 21.6% for PsA. In conclusion, reproductive lifespan, with its inherent homeostasis, plays a pivotal yet overlooked role in late-onset psoriatic diseases. Investigations into estrogen-centric causes and sex-specific interventions are imperative.

Associations Between Sex-Specific Reproductive Factors and Risk of New-Onset Lung Cancer Among Female Patients.

BACKGROUND: Several characteristics distinguish lung cancer in female patients from that in male patients, with adenocarcinoma being more prevalent in female patients and occurring more frequently in female patients who do not smoke. Uncertainty surrounds the relationship between female-specific reproductive factors and lung cancer risk. RESEARCH QUESTION: Are sex-specific reproductive factors associated with risk of lung cancer in different genetic risk groups and histologic types? STUDY DESIGN AND METHODS: A Cox proportional hazard model was used to evaluate the association between multiple reproductive factors and the risk of lung cancer developing in a prospective cohort study involving 273,190 female individuals from the UK Biobank. Subgroup analyses stratified by age, smoking status, BMI, genetic risk, and histologic subtype were conducted to emphasize the modification effects further. RESULTS: A total of 1,182 cases of lung cancer in female patients were recorded over a median follow-up period of 12.0 years in the cohort study. In multivariable-adjusted models, early menarche (age ≤ 11 years: hazard ratio [HR], 1.22; 95% CI, 1.03-1.46), early menopause (age ≤ 46 years: HR, 1.49; 95% CI, 1.19-1.86), a shorter reproductive span (≤ 32 years: HR, 1.42; 95% CI, 1.18-1.71; and 33-35 years: HR, 1.24; 95% CI, 1.00-1.53), and early age at first birth (age ≤ 20 years: HR, 1.63; 95% CI, 1.33-2.01) were associated with a higher risk of lung cancer. Stratified analysis revealed that several reproductive factors, including early age at menopause, shortened reproductive span, and early age at first birth, showed a substantially stronger relationship with an elevated risk of lung cancer, particularly of lung adenocarcinoma, in populations with high genetic risk and more detrimental behaviors. INTERPRETATION: Early age at menopause, a shortened reproductive life span, and early age at first birth were associated with higher risks of lung cancer, particularly of lung adenocarcinoma, in a subpopulation with higher genetic susceptibility and detrimental behaviors. The evidence provided by this study emphasizes the significance of screening for multiple reproductive factors to prevent lung cancer among female individuals.

Vitamin D Status, Vitamin D Receptor Polymorphisms, and the Risk of Incident Rosacea: Insights from Mendelian Randomization and Cohort Study in the UK Biobank.

BACKGROUND: Previous cross-sectional studies have failed to definitively establish a causal relationship between serum 25-hydroxyvitamin D (25OHD) concentrations and the onset of rosacea. OBJECTIVE: To investigate the potential association between serum 25OHD levels, vitamin D receptor (VDR) polymorphisms, and the risk of developing incident rosacea. METHODS: This cross-sectional population-based cohort study utilizing 370,209 individuals from the UK Biobank. Cox proportional hazard regression models and two-sample Mendelian randomization (MR) analyses were applied to explore the causative relationship between 25OHD and incident rosacea. RESULTS: Our findings revealed that elevated levels of serum 25OHD were inversely correlated with the risk of incident rosacea. Specifically, compared to participants with 25OHD levels below 25 nmol/L, the multivariate-adjusted HR for incident rosacea was 0.81 (95% CI: 0.70, 0.94) in those with 25OHD levels exceeding 50 nmol/L. Further, in comparison to individuals with serum 25OHD less than 25 nmol/L and the rs731236 (TaqI) AA allele, those with serum 25OHD higher than 75 nmol/L and the TaqI GG allele had a multivariate-adjusted HR of 0.51 (95% CI 0.32 to 0.81) for developing rosacea. Results from the MR study supported a significant association, with each standard deviation increase in serum 25OHD concentrations correlating to a 23% reduced risk of rosacea (HR = 0.77, 95% CI: 0.63, 0.93). CONCLUSIONS: The findings of this cohort study indicate an inverse association between increased concentrations of serum 25OHD and the risk of developing incident rosacea. While our results highlight the potential protective role of vitamin D, the definitive efficacy of vitamin D supplementation as a preventive strategy against rosacea requires further investigation.

Adenosine 5'monophosphate-activated protein kinase activation reduces the risks of psoriasis and its comorbidities: a mendelian randomisation study in the UK Biobank.

OBJECTIVE: Whether metformin and its adenosine 5'monophosphate-activated protein kinase (AMPK) activation protect from psoriasis risk is unconcluded. We investigated the effect of AMPK, a pharmacological target of metformin, on the risk of psoriasis and its comorbidities and mortality among participants in the UK Biobank(UKB). METHODS: To avoid immortal-time-biases in pharmacoepidemiologic studies, Mendelian randomisation was used to infer the AMPK pathway-dependent effects. The cut-off age for distinguishing early-onset/late-onset psoriasis (EOP/LOP) was set at 60 years, based on the incident psoriasis peak in UKB. A genetic instrument comprising 44 single-nucleotide polymorphisms associated with HbA1c, serving as a proxy for AMPK genetic risk score (negatively associated with AMPK activation), was employed as previously reported in the literature. Log-binomial models were used to estimate the effect size of AMPK regarding relative risk (RR) and 95% confidence interval (CI). RESULTS: A total of 407 159 participants were analyzed, including 9,126 EOP and 3,324 LOP. The AMPK-genetic-risk-score was associated with a 12.4% increase in the risk of LOP in men (RR = 1.124, 95% CI: 1.022-1.236). This association was not significant for EOP or women. AMPK genetic risk score exhibited an elevated risk of ischemic heart disease (RR = 1.217, 95% CI 1.062-1.395) in male psoriasis patients. CONCLUSIONS: AMPK activation may protect against LOPs and associated ischemic heart disease in men. A sex-specific, comorbidity-targeted intervention for psoriasis is needed.

Association of genetic risk and lifestyle with incident adult-onset asthma in the UK Biobank cohort.

Background: Both genetic and lifestyle factors contribute to the development of asthma, but whether unfavourable lifestyle is associated with similar increases in risk of developing asthma among individuals with varying genetic risk levels remains unknown. Methods: A healthy lifestyle score was constructed using body mass index, smoking status, physical activities and dietary pattern to further categorise into ideal, intermediate and poor groups. Genetic risk of asthma was also categorised as three groups based on the tertiles of polygenic risk score established using 212 reported and verified single-nucleotide polymorphisms of European ancestry in the UK Biobank study. We examined the risk of incident asthma related with each lifestyle level in each genetic risk group by Cox regression models. Results: Finally, 327 124 participants without baseline asthma were included, and 157 320 (48.1%) were male. During follow-up, 6238 participants (1.9%) developed asthma. Compared to ideal lifestyle in a low genetic risk group, poor lifestyle was associated with a hazard ratio of up to 3.87 (95% CI, 2.98-5.02) for developing asthma in a high genetic risk group. There was interaction between genetic risk and lifestyle, and the population-attributable fraction of lifestyle and genetic risk were 30.2% and 30.0% respectively. Conclusion: In this large contemporary population, lifestyle and genetic factors jointly play critical roles in the development of asthma, and the effect values of lifestyle on incident adult-onset asthma were greater than that of genetic risk. Our findings highlighted the necessity of a comprehensive intervention for the prevention of asthma despite the genetic risk.

Association of outdoor air pollution, lifestyle, genetic factors with the risk of lung cancer: A prospective cohort study.

OBJECTIVES: The effect of air pollution exposure on incident lung cancer remains uncertain, and the modifying role of lifestyle and genetic susceptibility in association between air pollution and lung cancer is ambiguous. METHODS: A total of 367,623 participants from UK biobank cohort were enrolled in the analysis. The concentrations of particle matter (PM2.5, PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx), were evaluated by land-use regression model. Cox proportional hazard model was applied to assess the associations between air pollution and incident lung cancer. A lifestyle risk score and a polygenic risk score were established to investigate whether lifestyle and heritable risk could modify the effect of air pollution on lung cancer risk. RESULTS: Per interquartile range (IQR) increment in annual concentrations of PM2.5 (HR = 1.22, 95% CI, 1.15∼1.30), NO2 (HR = 1.19, 95% CI, 1.10∼1.27), and NOx (HR = 1.14, 95% CI, 1.09∼1.20) were associated with increased risk of lung cancer. We observed an additive interaction between air pollution including PM2.5 and NOx and lifestyle or genetic risk. Individuals with high air pollution exposure, poor lifestyle and high genetic risk had the highest risk of incident lung cancer. CONCLUSION: Long-term exposures to air pollution is associated with increased risk of lung cancer, and this effect was modified by lifestyle or genetic risk. Integrated interventions for environmental pollution by government and adherence to healthy lifestyle by individuals are advocated for lung cancer prevention.

Association of Coffee and Tea Consumption with the Risk of Asthma: A Prospective Cohort Study from the UK Biobank.

Background: Previous observational studies investigated the relationship between coffee and tea intake and the risk of asthma, however, the conclusions were inconsistent. Further, the combined effect of coffee and tea consumption on asthma has rarely been studied. Methods: We examined associations between the self-reported intake of tea and coffee and the risk of incident asthma in a total of 424,725 participants aged from 39 to 73 years old from the UK Biobank. Cox proportional hazards models were used to estimate the associations between coffee/tea consumption and incident adult-onset asthma, adjusting for age, sex, race, smoking status, body mass index (BMI), education, and Townsend deprivation index. Results: Cox models with penalized splines showed J-shaped associations of coffee, tea, caffeinated coffee, and caffeine intake from coffee and tea with the risk of adult-onset asthma (p for nonlinear <0.01). Coffee intake of 2 to 3 cups/d (hazard ratio [HR] 0.877, 95% confidence interval [CI] 0.826−0.931) or tea intake of 0.5 to 1 cups/d (HR 0.889, 95% CI 0.816−0.968) or caffeinated coffee intake of 2 to 3 cups/d (HR 0.858, 95% CI 0.806−0.915) or combination caffeine intake from tea and coffee of 160.0 to 235.0 mg per day (HR 0.899, 95% CI 0.842−0.961) were linked with the lowest hazard ratio of incident asthma after adjustment for age, sex, race, smoking status, BMI, qualification, and Townsend deprivation index. Conclusions: Collectively, the study showed light-to-moderate coffee and tea consumption was associated with a reduced risk of adult-onset asthma and controlling total caffeine intake from coffee and tea for a moderate caffeine dose of 160.0 to 305.0 mg/day may be protective against adult-onset asthma. Further investigation on the possible preventive role of caffeine in asthma is warranted.

Associations of combined lifestyle and genetic risks with incident psoriasis: A prospective cohort study among UK Biobank participants of European ancestry.

BACKGROUND: Whether the lifestyle is associated with the risk of psoriasis in the presence of different genetic risk levels remains unknown. OBJECTIVE: To examine the gene-behavior interaction in association with incident psoriasis. METHODS: This study is based on the data from the UK Biobank, which recruited 500,000 participants. Genetic risk was categorized into low, intermediate, and high groups. The lifestyle score comprised the body mass index, smoking, physical activity, and diet and was also categorized into the ideal, intermediate, and poor groups. Within each genetic risk group, the risks of incident psoriasis associated with each lifestyle level were investigated and compared with the low genetic risk and ideal lifestyle group. RESULTS: Compared with the low genetic risk and ideal lifestyle group, the poor lifestyle and high genetic risk group was associated with a hazard ratio of up to 4.625 (95% confidence interval [CI], 2.920-7.348) for psoriasis. There was no interaction between genetic risk and lifestyle. The population attributable fractions of lifestyle and genetic risk were 32.2% (95% CI, 25.1%-38.6%) and 13.0% (95% CI, 3.2%-21.8%), respectively. LIMITATIONS: No verification in other independently ascertained populations. CONCLUSION: Lifestyle factors are predictive of the risk of incident psoriasis independent of genetic risk, and the relative impact of lifestyle factors was greater than that of genetic risk.

Patient-Reported Outcomes of Arsenic-Related Skin Lesions in China.

PURPOSE: Previous studies confirmed that chronic arsenic exposure could lead to pigmentary changes and hyperkeratosis. However, skin health-related quality of life (HRQoL) among people under lifetime arsenic exposure remains underappreciated. Our study is aimed at investigating several patient-reported outcomes in a population under chronic arsenic exposure. Patients and Methods. A cross-sectional study was conducted in communities in Shimen, China. Dermatologists performed skin examinations for participants. Patient-reported outcomes (PROs) included HRQoL, itch, sleep quality, and symptoms of anxiety and depression. The Dermatology Life Quality Index (DLQI) was used to measure skin HRQoL. The numerical rating scale (NRS) was used to measure the intensity of itching. Sleep disturbance was measured by Pittsburgh Sleep Quality Index (PSQI). Anxiety and depression were measured by two-item Generalized Anxiety Disorder (GAD-2) and Patient Health Questionnaire (PHQ-2), respectively. RESULTS: A total of 464 participants suffering from arsenic-related skin lesions finished the assessment of DLQI. Pigmentary changes and arsenical keratosis were not associated with the patient-reported outcomes except PHQ-2. Hair arsenic exceeding 1 µg/g was associated with higher itch NRS and DLQI (P < 0.05). Itch NRS (adjusted ß = 0.80, 95% CI: 0.70-0.90, P < 0.01) and hair arsenic concentration (adjusted ß = 0.12, 95% CI: 0.01-0.24, P < 0.05) were independently associated with the DLQI. CONCLUSION: HRQoL, sleep quality, and mental wellbeing are impaired in residents under chronic arsenic exposure. Itching and hair arsenic are independent risk factors for impaired HRQoL.

Associations of second-hand smoke exposure with hand eczema and atopic dermatitis among college students in China.

Smoking has been identified as a risk factor for atopic dermatitis and hand eczema, but less is known about the association of exposure to second-hand smoke (SHS) with hand eczema. The study aimed to investigate the association of SHS exposure with hand eczema and atopic dermatitis in a group of adolescents. We conducted a cross-sectional study among first-year college students. SHS exposure was measured by a self-administered questionnaire. Skin diseases were diagnosed by dermatologists in the field survey. Mixed models were used to estimate the associations. A total of 20,129 participants that underwent skin examination and a questionnaire survey were included in the analyses. The prevalence rates of atopic dermatitis and hand eczema were 3.86% and 3.35%, respectively. Crude and adjusted estimates consistently showed that exposure to SHS was significantly associated with atopic dermatitis and hand eczema in a dose-response manner. Attention deficit/hyperactivity disorder mediated minimal or no effect of SHS on hand eczema and atopic dermatitis. Subgroup analysis by type of hand eczema, and sensitivity analysis by excluding data with center effect showed consistent results. Exposure to SHS is an independent but modifiable risk factor for hand eczema and atopic dermatitis in adolescents.