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.

Arsenic exposure and pruritus: Evidence from observational, interventional, and mendelian randomization studies.

BACKGROUND: Pruritus is identified as an adverse drug reaction to arsenic trioxide, but the association of arsenic exposure with pruritus has not been investigated. METHODS: A cross-sectional study was conducted in Shimen, China. A Mendelian randomization analysis was conducted to confirm the causal relationship between genetically predicted percentages of monomethylated arsenic (MMA%) and dimethylated arsenic (DMA%) in urine with chronic pruritus in UK Biobank. A case-control study was then conducted to determine the biomarker for pruritus. Arsenite-treated mice were used to confirm the biomarker, and von Frey test was used to induce scratching bouts. Last, a randomized, double-blind, placebo-controlled trial was conducted to test the efficacy of naloxone in arsenic-exposed patients with pruritus in Shimen. RESULTS: Hair arsenic (µg/g) showed a dose-response relationship with the intensity of itch in 1079 participants, with odds ratios (OR) of 1.11 for moderate-to-severe itch (p = 0.012). The Mendelian randomization analysis confirmed the causal relationship, with ORs of 1.043 for MMA% (p = 0.029) and 0.904 for DMA% (p = 0.077) above versus under median. Serum ß-endorphin was identified as a significant biomarker for the intensity of itch (p < 0.001). Consistently, treatment with arsenite upregulated the level of ß-endorphin (p = 0.002) and induced scratching bouts (p < 0.001) in mice. The randomized controlled trial in 126 participants showed that treatment with sublingual naloxone significantly relieved the intensity of itch in arsenic-exposed participants in 2 weeks (ß = -0.98, p = 0.04). CONCLUSION: Arsenic exposure is associated with pruritus, and ß-endorphin serves as a biomarker of pruritus. Naloxone relieves pruritus in patients with arseniasis.

Associations Between Reproductive Factors and the Risk of Adult-Onset Asthma: A Prospective Cohort Study of European Ancestry.

BACKGROUND: Multiple studies showed sex discrepancies in the prevalence, incidence, and disease control of asthma. The relationships between different reproductive factors and the risk of asthma in females remain uncertain. DESIGN: A prospective cohort study recruited 239,701 female participants from the UK Biobank. The Cox proportional hazard model and multiple adjusted restricted cubic splines were used to evaluate the association between each reproductive factor and the risk of adult-onset asthma. KEY RESULTS: We observed that the association of age at menarche and age of menopause with adult-onset asthma risk presented as U-shaped, with multiple adjusted HRs for age at menarche being 1.129 (95% CI, 1.038-1.228) for ≤ 11 years old and 1.157 (95% CI, 1.058-1.265) for ≥ 15 years old referenced to 13 years old, and for age at menopause being 1.368 (1.237-1.512) for ≤ 46 years old and 1.152 (1.026-1.294) for ≥ 55 years old referenced to 50-52 years old. Early age at first live birth (≤ 20 years old), a greater number of miscarriages (≥ 2) or stillbirths (≥ 2), more children (≥ 4), and shorter reproductive years (≤ 32 years) were associated with elevated risk of asthma. In addition, history of hysterectomy or oophorectomy was associated with increased risk of adult-onset asthma, particularly in those with simultaneous hysterectomy and oophorectomy (HR, 1.239; 95% CI, 1.063-1.445). For exogenous sex hormones, hormone replacement therapy (HR, 1.482; 95% CI, 1.394-1.574) was identified to be associated with elevated risk of adult-onset asthma. CONCLUSIONS: This study not only demonstrated significant associations between multiple reproductive factors and the risk of adult-onset asthma in a female's later life, but also found that history of hysterectomy or oophorectomy, as well as hormone replacement therapy, was linked to an elevated incidence of adult-onset asthma. Our findings highlighted the significance of reproductive factors in the development of asthma in female populations.

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 air pollution and genetic risks with incidence of elderly-onset atopic dermatitis: A prospective cohort study.

BACKGROUND: Elderly-onset atopic dermatitis (AD) is a remarkable subtype and has been put on the agenda owing to its difficulty to control. Understanding the influence of genetic and environmental exposures is crucial to preventing elderly-onset AD. OBJECTIVES: To explore the association between genes and air pollution on incident elderly-onset AD. MATERIAL AND METHODS: This study was based on UK Biobank that recruited over 500,000 participants. The genetic risks were categorized into low, intermediate, and high groups according to tertiles of polygenic risk scores. Mixed exposure to various air pollutants was assessed using the weighted quantile sum (WQS) and also categorized based on tertiles. Within each genetic risk group, whether air pollutant mixture was associated with incident elderly-onset AD was estimated. RESULTS: 337,910 participants were included in the final analysis, and the mean age was 57.1. The median years for follow-up were 12.0, and the incident cases of AD were 2545. The medium and high air pollution mixture was significantly associated with incident AD compared with the low pollution group, with HRs of 1.182 (P = 0.003) and 1.359 (P < 0.001), respectively. In contrast, HR for medium and high genetic susceptibility was only 1.065 (P = 0.249) and 1.153 (P = 0.008). The population-attributable fraction of air pollution and genetic risk was 15.5 % (P < 0.001) and 6.4 % (P = 0.004). Additionally, compared with low genetic risk and low air pollution, high genetic risk and high air pollution was significantly associated with the incidence of elderly-onset AD with a HR of up to 1.523 (P < 0.001). There were no interactive effects between each group of genetic risks and air pollution. When grouped by sex, females could observe a stronger effect by genetic and air pollutant mixture exposure. CONCLUSION: Air pollution and genetics both independently enhance the risk of newly developed AD, and the effect of air pollutants is stronger than the investigated genes.

Association of air pollution, genetic risk, and lifestyle with incident adult-onset asthma: A prospective cohort study.

BACKGROUND: Numerous studies have explored the association of air pollution with asthma but have yielded conflicting results. The exact role of air pollution in the incidence of adult-onset asthma and whether this effect is modified by genetic risk, lifestyle, or their interaction remain uncertain. METHODS: We conducted a prospective cohort study on 298,738 participants (aged 37-73 years) registered in the UK Biobank. Cox proportional hazard models were used to evaluate the association of air pollution, including particulate matter (PM2.5, PMcoarse, and PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx), with asthma incidence. We constructed genetic risk and lifestyle scores, assessed whether the impact of air pollution on adult-onset asthma risk was modified by genetic susceptibility or lifestyle factors, and evaluated the identified interactions. RESULTS: We found that each interquartile range increase in annual concentrations of PM2.5, NO2, and NOx was related to 1.04 (95% confidence interval [CI]: 1.01, 1.08), 1.04 (95% CI: 1.00, 1.08), and 1.03 (95% CI: 1.00, 1.06) times the risk of adult-onset asthma, respectively. The size of the effect of air pollution was greater among subpopulations with low genetic risk or unfavorable lifestyles. We also identified an additive interaction effect of air pollution with lifestyle factors, but not with genetic risk, on the risk of adult-onset asthma. CONCLUSION: Our analyses show that air pollution increases the risk of adult-onset asthma, but that the size of the effect is modified by lifestyle and genetic risk. These findings emphasize the need for integrated interventions for environmental pollution by the government as well as adherence to healthy lifestyles to prevent adult-onset asthma.

Lachnospira is a signature of antihistamine efficacy in chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) is a mast cell-driven disease with many advances in its aetiology and pathogenesis over the past years. The main treatment of CSU is oral second-generation antihistamines. However, only an average of 50% of CSU patients responded adequately to conventional or quadruple doses of non-sedative antihistamines. Meanwhile, gut microbiota can affect the efficacy of drugs. The purpose of this study was to investigate the relationship between gut microbiota and the efficacy of antihistamines in patients with CSU. The patients with CSU were divided into responders and non-responders according to the efficacy of antihistamine monotherapy. The gut microbiota of faecal samples from 15 responders and 15 non-responders was detected by 16S rDNA sequencing, and the differential bacterial species between the two groups were verified by quantitative polymerase chain reaction (qPCR). Additional faecal samples from 30 responders and 30 non-responders were used as an extended cohort to further verify the above differential bacterial species by qPCR. Lachnospiraceae and its subordinate taxa were found to be the main differences in gut microbiota between responders and non-responders. The abundance of Lachnospira in responders was higher than that in non-responders. Lachnospira exhibits moderate diagnostic value in evaluating the efficacy of antihistamine. Lachnospira is a signature for predicting the efficacy of antihistamine in patients with CSU.

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.

Identification of gut microbiota signatures in symptomatic dermographism.

Symptomatic dermographism (SD) is a recurrent inflammatory skin disease related to immunity; however, the details remain elusive. In view of the important role of gut microbiota in immune regulation, the purpose of this study is to investigate the alterations of gut microbiota in SD and explore the potential bacterial biomarkers for diagnosis. A case-control study including SD patients and normal controls (NCs) was carried out. Gut microbiota of the participants was analysed by the 16S rDNA sequencing of faecal samples. The linear discriminant analysis effect size and the receiver operating characteristic curve (ROC) analysis were used to identify the bacterial biomarkers. Forty-four participants were included in this study. The alpha-diversity and beta-diversity of gut microbiota differed significantly between SD patients and NCs. The abundance of Verrucomicrobia, Ruminococcaceae and their subordinate taxa were reduced in SD patients, while Enterobacteriales and its subordinate taxon exhibited higher relative abundance compared with NCs. Subdoligranulum and Ruminococcus bromii showed a potential diagnostic value for SD, and Prevotella stercorea was negatively relevant to duration of SD. Furthermore, the pyruvate, butyric acid and histamine metabolism pathway were likely to be involved in the pathogenesis of SD. Our results revealed that the gut microbiota of SD patients experienced obvious changes, and Verrucomicrobia, Ruminococcaceae and Enterobacteriales were microbiota signatures for SD.

Daily Intake of Soft Drinks and Moderate-to-Severe Acne Vulgaris in Chinese Adolescents.

OBJECTIVES: To investigate the association of soft drink consumption and the intake of sugar from soft drinks with the prevalence of acne in adolescents. STUDY DESIGN: This was a university-based epidemiologic investigation that included 8226 students who underwent health examinations and a questionnaire survey inquiring about the intake of soft drinks. Skin diseases were diagnosed by certificated dermatologists during the health examination. Two-level logistic and generalized additive models were used to estimate the associations, and aORs were presented as the effect size. RESULTS: A total of 8197 student survey responses were analyzed. Frequent intake (≥7 times per week) of carbonated sodas (aOR 1.61, 95% CI 0.96-2.72), sweetened tea drinks (aOR 2.52, 95% CI 1.43-4.43), and fruit-flavored drinks (aOR 1.90, 95% CI 1.18-3.07) was associated with moderate-to-severe acne after adjustments for confounders. The occasional intake of fruit-flavored drinks (1-2 times per week) had a weak protective effect on acne (aOR 0.86, 95% CI 0.74-0.99). The intake of sugar from any soft drinks showed a nonlinear association with acne (P < .01), and sugar intake ≥100 g/d was significantly associated with moderate-to-severe acne (aOR 3.12, 95% CI 1.80-5.41). CONCLUSIONS: Daily soft drink consumption significantly increases the risk of moderate-to-severe acne in adolescents, especially when the sugar intake from any type of soft drink exceeds 100 g per day.

The Prevalence of Atopic Dermatitis and Chronic Spontaneous Urticaria are Associated with Parental Socioeconomic Status in Adolescents in China.

The association of atopic dermatitis and chronic spontaneous urticaria with socioeconomic status has been little studied. The aim of this study was to investigate the prevalence of skin diseases and their association with socioeconomic status in adolescents in China. A cross-sectional study was conducted at Central South University, Changsha, China. All newly enrolled students underwent dermatological examination and completed a survey. Socioeconomic status was measured in terms of parental education level and income. Two-level logistic regression models were used. A total of 8,226 students consented to participate. On dermatological examination, moderate to severe acne (10.2%) had the highest prevalence, followed by chronic spontaneous urticaria (2.7%), atopic dermatitis (2.5%), and tinea (1.7%). Socioeconomic status was positively associated with the prevalence of chronic spontaneous urticaria (ptrend = 0.001) and atopic dermatitis (ptrend = 0.0094). Tinea was inversely associated with socioeconomic status (ptrend = 0.025). Higher parental socioeconomic status was associated with higher risk of atopic dermatitis and chronic spontaneous urticaria, but lower risk of tinea.

Daily intake of soft drinks is associated with symptoms of anxiety and depression in Chinese adolescents.

OBJECTIVE: The association of soft drink consumption with mental problems in Asian adolescents has not been reported. The present study aimed to investigate the association of soft drink consumption and symptoms of anxiety and depression in adolescents in China. DESIGN: A cross-sectional study to investigate the association of intake of soft drinks and sugars from soft drinks with symptoms of anxiety and depression measured by the two-item Generalized Anxiety Disorder (GAD-2) and the Patient Health Questionnaire (PHQ-2), respectively. SETTING: A comprehensive university in Changsha, China. PARTICIPANTS: Newly enrolled college students in 2017. RESULT: In total, 8226 students completed the investigation and 8085 students with no systemic disorders were finally analysed. Students consuming soft drinks ≥7 times/week had significantly higher (mean difference; 95 % CI) GAD-2 (0·15; 0·07, 0·23) and PHQ-2 (0·27; 0·19, 0·35) scores compared with those barely consuming soft drinks, adjusted for demographic and behavioural factors. Those consuming >25 g sugar/d from soft drinks had significantly higher GAD-2 (0·11; 0·04, 0·18) and PHQ-2 (0·22; 0·15, 0·29) scores compared with non-consumers. The mediation effect of obesity in the associations was not clinically significant. CONCLUSIONS: Adolescents consuming soft drinks ≥7 times/week, or >25 g sugar/d from soft drinks, had significantly higher levels of anxiety and depression. Dietary suggestion is needed to prevent anxiety and depression in adolescents.

Assessment of the Dermatology Life Quality Index (DLQI) in a homogeneous population under lifetime arsenic exposure.

PURPOSE: The psychometric property of the Dermatology Life Quality Index (DLQI) is underappreciated in public health settings. Our study aimed to assess the reliability, validity, and measurement invariance of DLQI in a homogeneous population with arsenic-related skin lesions and symptoms. METHODS: A cross-sectional study was conducted in communities under lifetime arsenic exposure. The DLQI was measured through a face-to-face interview. Skin examinations were performed by certificated dermatologists. The intensity of itching was measured by a numerical rating scale. Reliability, structural validity, and measurement invariance were determined using classical and modern test theories, including confirmatory factor analysis and item response models. RESULTS: 465 participants with arsenic-related skin lesions and symptoms completed the DLQI assessment. The Cronbach's alpha was 0.79, and the split-half reliability was 0.77. A two-factor model exhibited the best model fit among models evaluated, but local dependencies among items were identified. The model showed good root mean square error of approximation (0.031) and acceptable Tucker-Lewis index (0.92). Multi-group confirmatory factor analysis showed no measurement invariance across subgroups of age, gender, ethnicity, and intensity of itching. CONCLUSIONS: The DLQI had acceptable psychometric properties, but measurement invariance was not observed across different groups of participants.

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.

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.

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.

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.