Endometriosis, Psoriasis, and Psoriatic Arthritis: A Prospective Cohort Study.

Endometriosis, psoriasis, and psoriatic arthritis (PsA) are chronic inflammatory disorders whose etiologies remain poorly understood but may be correlated, as endometriosis has been associated with other inflammatory disorders. We investigated the bidirectional associations between laparoscopically confirmed endometriosis and physician-diagnosed psoriasis and PsA in the Nurses' Health Study II cohort (n = 116,429, United States, 1991-2013). We confirmed 4,112 incident cases of laparoscopically confirmed endometriosis (mean age at diagnosis = 40.3 years) and 697 validated physician-diagnosed cases of psoriasis (mean age at diagnosis = 43.6 years), 110 of which presented with concomitant PsA. A history of psoriasis with concomitant PsA was associated with a 2-fold higher risk of endometriosis (hazard ratio (HR) = 2.01, 95% CI: 1.23, 3.30); however, no association was observed between psoriasis without PsA and endometriosis risk (HR = 0.93, 95% CI: 0.68, 1.26). When endometriosis was the exposure, it was not associated with a risk of subsequent psoriasis (HR = 1.28, 95% CI: 0.95, 1.72). The risk of psoriasis with PsA was notably higher; however, the sample size was small and the confidence intervals wide (HR = 1.77, 95% CI: 0.89, 3.52). Our findings suggest that psoriasis with concomitant PsA is associated with greater risk of laparoscopically confirmed endometriosis. In addition, there was a suggestive association between endometriosis diagnosis and subsequent risk of psoriasis with PsA.

Eye color and the risk of skin cancer.

Melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common skin cancers. The incidence rates of all three types of skin cancers have increased in the past three decades. Light pigmentary traits have been recognized as one of the host risk factors for skin cancer, but findings on associations between eye colors and risk of skin cancers have been inconsistent.We performed a prospective analysis to examine the association between eye colors and risk of skin cancers using the Health Professionals Follow-up Study (HPFS). Cox proportional hazard models were applied to estimate relative risks (RRs) and their 95% confidence intervals (CIs). Effect modifications due to hair color and skin reaction to sun were also examined.The HPFS included 35,662 males. During a median follow-up of 19 years (1988-2012), 445 melanoma, 1123 SCC, and 7198 BCC cases were documented. Compared to those whose eye colors were dark or brown, participants with hazel/green/medium and blue/light colors had a 24% (RR = 1.24, 95% CI: 1.06-1.45) and a 19% (RR = 1.19, 95% CI: 1.01-1.41) higher risk of SCC, respectively. Similarly, a higher risk of BCC was observed in participants with hazel/green/medium eye colors (RR = 1.16, 95% CI: 1.09-1.23) and blue/light eye colors (RR = 1.17, 95% CI: 1.10-1.25). We did not find significant associations between eye color and risk of melanoma. Lighter eye color was associated with increased risks of SCC and BCC among those with dark hair colors (p for interaction ≤ 0.02).In conclusion, in this large prospective study of men, we found that light eye colors were associated with higher risks of SCC and BCC, but not melanoma. Further studies are needed to confirm this association in other populations.

COX-2 inhibitors show no preventive effect in the development of skin cancer.

BACKGROUND: Some clinical trials found that cyclooxygenase-2 (COX-2) inhibitor use lowered the risk of skin cancer in high-risk groups. PATIENTS AND METHODS: To determine whether COX-2 inhibitor use is associated with lower risk of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma, we analyzed COX-2 inhibitor use and risk of skin cancer based on three prospective cohort studies, the Nurses' Health Study (NHS), NHS II, and the Health Professionals Follow-up Study, including 153,882 participants. Multivariable hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association of COX-2 inhibitor use with risk of BCC, cSCC, and melanoma were estimated using Cox proportional hazards models. We pooled the results using a fixed effects model. RESULTS: 16,142 BCC, 1,973 cSCC, and 631 melanoma cases were documented. Ever vs. never use of COX-2 inhibitor was associated with a modestly increased risk of BCC (multivariable HR 1.09, 95 % CI 1.05-1.14). The hazard ratio was similar for cSCC (multivariable HR 1.12, 95 % CI 1.00-1.27) and melanoma (multivariable HR 1.10, 95 % CI 0.89-1.38), but was not statistically significant. CONCLUSIONS: Ever use of COX-2 inhibitor was not associated with a decreased skin cancer risk but was instead associated with a modest, increased risk of BCC.

Gluten intake and risk of psoriasis, psoriatic arthritis, and atopic dermatitis among United States women.

BACKGROUND: Associations between gluten intake and psoriasis, psoriatic arthritis, and atopic dermatitis are poorly understood. OBJECTIVE: To determine whether increased gluten intake is associated with incident psoriasis, psoriatic arthritis, and atopic dermatitis. METHODS: Cohort studies among women in Nurses' Health Study II. Food frequency questionnaires were used to calculate gluten content of participants' diet every 4 years (1991-2015 for psoriatic disease, 1995-2013 for atopic dermatitis). Disease outcomes were assessed by self-report and subsequently validated. Multivariable-adjusted Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for the association between gluten intake (quintiles) and psoriasis, psoriatic arthritis, and atopic dermatitis. RESULTS: We included 85,185 participants in the psoriasis analysis, 85,324 in the psoriatic arthritis analysis, and 63,443 in the atopic dermatitis analysis. Increased gluten intake was not associated with any of the outcomes (all P for trend >.05). Comparing highest and lowest gluten intake quintiles, the multivariable hazard ratios (95% confidence intervals) were 1.15 (0.98-1.36) for psoriasis, 1.12 (0.78-1.62) for psoriatic arthritis, and 0.91 (0.66-1.25) for atopic dermatitis. LIMITATIONS: No assessment of a strictly gluten-free diet. CONCLUSIONS: Our findings do not support the amount of dietary gluten intake as a risk factor for psoriasis, psoriatic arthritis, or atopic dermatitis in adult women.

Inflammatory dietary pattern and incident psoriasis, psoriatic arthritis, and atopic dermatitis in women: A cohort study.

BACKGROUND: Diet is a modulator of inflammation that might impact inflammatory skin diseases. OBJECTIVE: To assess the relationship between pro-inflammatory dietary patterns and incident psoriasis, psoriatic arthritis (PsA), and atopic dermatitis (AD). METHODS: We conducted cohort studies among women in the Nurses' Health Study II. The Empirical Dietary Inflammatory Pattern (EDIP) score was calculated at baseline and every 4 years. Incident psoriasis, PsA, and AD were assessed by validated self-report. We used multivariable-adjusted Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between EDIP quintiles and risk for psoriasis, PsA, and AD. RESULTS: We had 85,185 participants in the psoriasis analysis and 63,443 in the AD analysis. There were 1432 cases of psoriasis, 262 cases of PsA, and 403 cases of AD. Pro-inflammatory dietary patterns were not associated with the risk for outcomes in multivariable models (all P values for trend >.05). HRs comparing the highest to the lowest EDIP quintile were 0.99 (95% CI 0.83-1.18) for psoriasis, 1.22 (95% CI 0.81-1.83) for PsA, and 0.96 (95% CI 0.69-1.34) for AD. LIMITATIONS: Recall and self-report. CONCLUSION: Our findings do not support dietary inflammatory potential as a risk factor for psoriasis, PsA, or AD.

Red meat and processed meat intake and risk for cutaneous melanoma in white women and men: Two prospective cohort studies.

BACKGROUND: Red and processed meat consumption has been associated with increased risk for several cancers, but the association with cutaneous melanoma risk has been inconclusive. OBJECTIVE: To investigate the association between red and processed meat intake and melanoma risk. METHODS: Dietary information was assessed by using food frequency questionnaires in 2 prospective cohorts: 75,263 women from the Nurses' Health Study (1984-2010) and 48,523 men from the Health Professionals Follow-up Study (1986-2010). Melanoma cases were confirmed by reviewing pathology records. Pooled multivariable hazard ratios and 95% confidence intervals were estimated by using Cox proportional hazards models. RESULTS: A total of 679 female and 639 male melanoma cases were documented during follow-up. Red and processed meat intake was inversely associated with melanoma risk (P = .002 for trend); the pooled hazard ratios (95% confidence intervals) of the 2 cohorts were 1.00 (reference), 1.00 (0.87-1.14), 0.98 (0.86-1.13), 0.89 (0.77-1.02), and 0.81 (0.70-0.95) for increasing quintiles of intake. LIMITATIONS: Findings might have limited generalizability, considering that the cohorts were limited to white health professionals. CONCLUSION: Red and processed meat intake was inversely associated with melanoma risk in these 2 cohorts.

Niacin intake and risk of skin cancer in US women and men.

A recent clinical trial found a protective role of niacinamide, a derivative of niacin, against skin cancer recurrence. However, there is no epidemiologic study to assess the association between niacin intake and risk of skin cancer [basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma]. We prospectively evaluated whether total, dietary and supplemental niacin intake was associated with skin cancer risk based on 72,308 women in the Nurses' Health Study (1984-2010) and 41,808 men in the Health Professionals Follow-up Study (1986-2010). Niacin intake was assessed every 2 to 4 years during follow-up and cumulative averaged intake. Cox proportional hazard models were used to compute the hazard ratios (HR) and 95% confidence intervals (CI) and cohort-specific results were pooled using a random-effects model. During the follow-up, we documented 23,256 BCC, 2,530 SCC and 887 melanoma cases. Total niacin intake was inversely associated with SCC risk; the pooled HR for top vs. bottom quintiles was 0.84 (95% CI = 0.74-0.95; ptrend = 0.08). However, there were a marginally positive association between total niacin intake and BCC risk; the pooled HR for top versus bottom quintiles was 1.05 (95% CI = 1.01-1.10; ptrend < 0.01). Higher total niacin intake was also marginally positively associated with melanoma risk in men, but not in women. The results were similar in stratified analyses according to sun exposure related factors and by body location of melanoma and SCC. Our study supports a potential beneficial role of niacin intake in relation to SCC but not of BCC or melanoma.

Alcohol Intake is Associated with Increased Risk of Squamous Cell Carcinoma of the Skin: Three US Prospective Cohort Studies.

The association between alcohol intake and cutaneous squamous cell carcinoma (cSCC) is unclear. We studied the association between alcohol intake and incident invasive cSCC in three cohorts of women and men with repeated assessments of alcohol intake in the US. Information on alcohol intake was collected repeatedly during follow-up. Cumulative average of alcohol intakes was used. Multivariable Cox proportional hazards models with time-dependent exposure were used to estimate relative risks (RRs) and 95% confidence intervals, followed by a meta-analysis. During a follow-up of 4,234,416 person-years, 2,938 cSCC were identified. Alcohol intake was associated with an increased risk of cSCC with a dose-response relationship. Each additional drink (12.8 gram of alcohol) per day was associated with a 22% increased risk of cSCC (RR 1.22, 95% confidence interval: 1.13-1.31). White wine consumption of ≥5 times/wk was associated with an increased risk of cSCC (RR 1.31, 95% confidence interval: 1.09-1.59). We found no increased risk of cSCC with other alcoholic beverages. The population-attributable risk associated with alcohol intake of ≥20 grams/d was 3% of cSCCs. In conclusion, alcohol intake was associated with an elevated risk of cSCC. Among alcoholic beverages, white wine was associated with cSCC.

Trends in the diagnosis and clinical features of melanoma in situ (MIS) in US men and women: A prospective, observational study.

BACKGROUND: The incidence of melanoma in situ (MIS) is increasing, but little is known about its clinical and epidemiologic features. OBJECTIVE: We sought to determine trends in diagnosis and clinical features of MIS. METHODS: Incident cases of melanoma were collected prospectively from the Nurses' Health Study (1976-2010) and Health Professionals Follow-up Study (1986-2010). RESULTS: MIS incidence increased from 2 to 42 per 100,000 person-year among women, and from 11 to 73 per 100,000 person-year among men, exceeding the rate of increase of invasive melanomas. Melanoma mortality initially increased during the follow-up period then plateaued. Men were more likely than women to develop in situ melanomas on the upper half of the body (P < .001). Invasive melanomas were diagnosed at a younger age than MIS (P < .001), and were more likely to be found on the lower extremities than MIS (P < .001). LIMITATIONS: This is a strictly descriptive study without examination into mechanisms. CONCLUSION: We found epidemiologic and clinical differences for in situ and invasive melanomas, which support further examination into the variations in etiologic pathways. The lack of improvement in mortality despite the increase in detection of in situ relative to invasive lesions further highlights the need to improve invasive melanoma-specific clinical screening features.

Host risk factors, ultraviolet index of residence, and incident malignant melanoma in situ among US women and men.

The incidences of malignant melanoma in situ (MMIS) and invasive malignant melanoma are rising in the United States, but few studies have examined risk factors for MMIS. We evaluated the risk of MMIS according to the host phenotype and the ultraviolet index of the state of residence. Prospective data were collected via biennial questionnaires from 250,151 women and men aged ≥20 years in the Nurses' Health Study (1980-2008), the Nurses' Health Study 2 (1989-2009), and the Health Professionals Follow-up Study (1986-2008). During 7,144,820 person-years of follow-up, 888 incident MMIS lesions occurred, representing 33% of all incident malignant melanoma. Meta-analysis across the cohorts demonstrated that the presence of multiple nevi on the extremities conferred the highest relative risk for MMIS (relative risk = 3.18, 95% confidence interval: 2.59, 3.90). Family history of melanoma, number of severe sunburns, sunburn susceptibility, hair color, and Fitzpatrick skin types I, II, and III were significantly associated with an increased risk of MMIS. Conversely, the ultraviolet index of the state of residence at birth, at age 15 years, and at age 30 years was not associated with increased risk of MMIS. Continued study of MMIS and associated risk factors will help identify persons who are most at risk and elucidate the role of MMIS within the spectrum of cutaneous melanoma.

Basal-cell carcinoma incidence and associated risk factors in U.S. women and men.

There is a paucity of data on basal-cell carcinoma (BCC) in the United States, since most national registries do not collect information on BCC. We evaluated BCC incidence trends and associated risk factors for BCC in 140,171 participants from a U.S. female cohort, the Nurses' Health Study (1986-2006), and a U.S. male cohort, the Health Professionals' Follow-up Study (1988-2006). Age-adjusted BCC incidence rates increased from 519 cases per 100,000 person-years to 1,019 cases per 100,000 person years for women and increased from 606 cases per 100,000 person-years to 1,488 cases per 100,000 person-years for men during the follow-up period. Cox proportional hazards analysis identified the following phenotypic risk factors for BCC in both cohorts: family history of melanoma, blond or red hair colors, higher number of extremity moles, higher susceptibility to sunburn as a child/adolescent, and higher lifetime number of severe/blistering sunburns. The multivariate-adjusted risk ratio for the highest quintile of cumulative midrange ultraviolet B flux exposure versus the lowest quintile was 3.18 (95% confidence interval: 2.70, 3.76) in women and 1.90 (95% confidence interval: 1.57, 2.29) in men. BCC incidence was generally higher in men than in women, and BCC risk was strongly associated with several phenotypic and exposure factors, including midrange ultraviolet B radiation, in our study populations.

Periodontal disease and risk of psoriasis among nurses in the United States.

OBJECTIVE: Periodontal disease has been associated with systemic inflammation and may be a risk factor for autoimmune diseases. This study evaluated the association between periodontal disease and the risk of incident psoriasis in a large prospective cohort study. MATERIAL AND METHODS: Self-reported history of periodontal bone loss, from 1998-2008, was evaluated as a risk factor for incident psoriasis among 60,457 women in the Nurses' Health Study. Secondary analyses examined associations between history of tooth loss and number of natural teeth and psoriasis risk. Cox proportional hazards models were used to assess multivariate estimates, adjusting for age, cigarette smoking, body mass index, alcohol intake and physical activity. RESULTS: An increased multivariate risk of psoriasis was observed for those with mild periodontal bone loss (RR = 1.35, 95% CI = 1.03-1.75) and moderate-to-severe periodontal bone loss (RR = 1.49, 95% CI = 1.08-2.05), as compared to those without periodontal bone loss, after adjusting for age, cigarette smoking, body mass index, alcohol intake, physical activity and tooth loss. Number of natural teeth and tooth loss were not associated with risk of psoriasis in this study. CONCLUSION: This study shows that a history of periodontal bone loss may increase risk of subsequent psoriasis. A limitation of this study is that it is based on self-reported measures.

The liver toxicity biomarker study phase I: markers for the effects of tolcapone or entacapone.

The Liver Toxicity Biomarker Study is a systems toxicology approach to discover biomarkers that are indicative of a drug's potential to cause human idiosyncratic drug-induced liver injury. In phase I, the molecular effects in rat liver and blood plasma induced by tolcapone (a "toxic" drug) were compared with the molecular effects in the same tissues by dosing with entacapone (a "clean" drug, similar to tolcapone in chemical structure and primary pharmacological mechanism). Two durations of drug exposure, 3 and 28 days, were employed. Comprehensive molecular analysis of rat liver and plasma samples yielded marker analytes for various drug-vehicle or drug-drug comparisons. An important finding was that the marker analytes associated with tolcapone only partially overlapped with marker analytes associated with entacapone, despite the fact that both drugs have similar chemical structures and the same primary pharmacological mechanism of action. This result indicates that the molecular analyses employed in the study are detecting substantial "off-target" markers for the two drugs. An additional interesting finding was the modest overlap of the marker data sets for 3-day exposure and 28-day exposure, indicating that the molecular changes in liver and plasma caused by short- and long-term drug treatments do not share common characteristics.