Shaowei Wu

Hypercholesterolemia and Risk of Incident Psoriasis and Psoriatic Arthritis in US Women

Psoriasis is a systemic inflammatory disorder associated with an increased risk of cardiovascular disease. Hypercholesterolemia is a major risk factor for cardiovascular disease, and patients with psoriasis or psoriatic arthritis (PsA) have been shown to have elevated cholesterol levels. However, it is not known whether hypercholesterolemia is associated with an increased risk of psoriasis or psoriasis with PsA. We undertook this study to determine whether a history of hypercholesterolemia is associated with the risk of developing incident psoriasis and psoriasis with PsA in a cohort of US women.

Psoriasis, psoriatic arthritis and risk of gout in US men and women

Background and objective Individuals with psoriasis have increased blood levels of uric acid. However, there is no prospective data on the association between psoriasis and uric acid levels and subsequent development of gout. In this study, we examined the risk of gout among individuals with psoriasis and psoriatic arthritis (PsA) in two cohorts of men and women, the Health Professionals Follow-up Study (HPFS) (1986–2010) and Nurses’ Health Study (NHS) (1998–2010). Methods 27 751 men and 71 059 women were included in the analysis. Lifetime history of physician-diagnosed incident psoriasis and PsA was confirmed by validated supplementary questionnaires. Incident gout diagnoses were confirmed based on the American College of Rheumatology survey criteria. We used Cox proportional hazards models controlling for potential risk factors to calculate the HRs with 95% CIs of incident gout while simultaneously adjusting for several common risk factors. Results We documented 2217 incident cases of gout during follow-up. Psoriasis was associated with an increased risk of subsequent gout with a multivariate HR of 1.71 (95% CI 1.36 to 2.15) in the pooled analysis. Risk of gout was substantially augmented among those with psoriasis and concomitant PsA (pooled multivariate HR: 4.95, 95% CI 2.72 to 9.01) when compared to participants without psoriasis. Conclusions In this prospective study of US women and men, psoriasis and PsA were associated with an increased risk of gout.

Cumulative ultraviolet radiation flux in adulthood and risk of incident skin cancers in women.

Background:Solar ultraviolet (UV) exposure estimated based on residential history has been used as a sun exposure indicator in previous case–control and descriptive studies. However, the associations of cumulative UV exposure based on residential history with different skin cancers, including melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC), have not been evaluated simultaneously in prospective studies.Methods:We conducted a cohort study among 108 578 women in the Nurses’ Health Study (1976–2006) to evaluate the relative risks of skin cancers with cumulative UV flux based on residential history in adulthood.Results:Risk of SCC and BCC was significantly lower for women in lower quintiles vs the highest quintile of cumulative UV flux (both P for trend <0.0001). The association between cumulative UV flux and risk of melanoma did not reach statistical significance. However, risk of melanoma appeared to be lower among women in lower quintiles vs the highest quintile of cumulative UV flux in lag analyses with 2–10 years between exposure and outcome. The multivariable-adjusted hazard ratios per 200 × 10−4 Robertson–Berger units increase in cumulative UV flux were 0.979 (95% confidence interval (CI): 0.933, 1.028) for melanoma, 1.072 (95% CI: 1.041, 1.103) for SCC, and 1.043 (95% CI: 1.034, 1.052) for BCC.Conclusions:Associations with cumulative UV exposure in adulthood among women differed for melanoma, SCC, and BCC, suggesting a potential variable role of UV radiation in adulthood in the carcinogenesis of the three major skin cancers.

Caffeine Intake, Coffee Consumption, and Risk of Cutaneous Malignant Melanoma.

Background: Caffeine has been shown to prevent ultraviolet radiation-induced carcinogenesis and to inhibit growth of melanoma cells in experimental studies. We evaluated the association among caffeine intake, coffee consumption, and melanoma risk among three large cohort studies. Methods: The analysis used data from 89,220 women in the Nurses’ Health Study II (1991–2009), 74,666 women in the Nurses’ Health Study (1980–2008), and 39,424 men in the Health Professionals Follow-up Study (1986–2008). We used Cox proportional hazards models to estimate the hazard ratios (HR) with 95% confidence intervals (CIs) of melanoma associated with dietary intakes. Results: We documented 2,254 melanoma cases over 4 million person-years of follow-up. After adjustment for other risk factors, higher total caffeine intake was associated with a lower risk of melanoma (≥393 mg/day vs. <60 mg/day: HR = 0.78, 95% CI = 0.64, 0.96; Ptrend = 0.048). The association was more apparent in women (≥393 mg/day vs. <60 mg/day: HR = 0.70, 95% CI = 0.58, 0.85; Ptrend = 0.001) than in men (HR = 0.94, 95% CI = 0.75, 1.2; Ptrend = 0.81), and more apparent for melanomas occurring on body sites with higher continuous sun exposure (head, neck, and extremities; ≥393 mg/day vs. <60 mg/day: HR = 0.71, 95% CI = 0.59, 0.86; Ptrend = 0.001) than for melanomas occurring on body sites with lower continuous sun exposure (trunk including shoulder, back, hip, abdomen, and chest; HR = 0.90, 95% CI = 0.70, 1.2; Ptrend = 0.60). This pattern of association was similar to that for caffeinated coffee consumption, whereas no association was found for decaffeinated coffee consumption and melanoma risk. Conclusions: Increasing caffeine intake and caffeinated coffee consumption is associated with decreased risk of cutaneous malignant melanomas.

Alcohol intake and risk of incident psoriatic arthritis in women.

Objective. Alcohol intake has been associated with an increased risk of psoriasis. However, the association between alcohol intake and risk of psoriatic arthritis (PsA) has been unclear. We evaluated the association between alcohol intake and risk of incident PsA in a large cohort of US women. Methods. Our present study included a total of 82,672 US women who provided repeated data on alcohol intake over the followup period (1991–2005). Self-reported PsA was validated using the Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire. Cox proportional hazards models were used to estimate the age-adjusted and multivariate-adjusted HR and 95% CI for the PsA in association with alcohol intake. Results. We documented 141 incident PsA cases during 14 years (1,137,763 person-yrs) of followup. Compared to non-drinkers, the multivariate HR for PsA were 0.70 (95% CI 0.48–1.01) for 0.1–14.9 g/day, 1.43 (95% CI 0.67–3.08) for 15.0–29.9 g/day, and 4.45 (95% CI 2.07–9.59) for ≥ 30.0 g/day of cumulative average alcohol intake. Risk estimates were generally consistent when using updated alcohol intake and baseline alcohol intake in 1991 as the exposures, and when the analysis was restricted to those who developed psoriasis during the followup. Conclusion. Excessive alcohol intake was associated with an increased risk of incident PsA in a cohort of US women.

ZBTB7A Suppresses Melanoma Metastasis by Transcriptionally Repressing MCAM.

The excessive metastatic propensity of melanoma makes it the most deadly form of skin cancer, yet the underlying mechanism of metastasis remains elusive. Here, mining of cancer genome datasets discovered a frequent loss of chromosome 19p13.3 and associated downregulation of the zinc finger transcription factor ZBTB7A in metastatic melanoma. Functional assessment of ZBTB7A-regulated genes identified MCAM, which encodes an adhesion protein key to melanoma metastasis. Using an integrated approach, it is demonstrated that ZBTB7A directly binds to the promoter and transcriptionally represses the expression of MCAM, establishing ZBTB7A as a bona fide transcriptional repressor of MCAM. Consistently, downregulation of ZBTB7A results in marked upregulation of MCAM and enhanced melanoma cell invasion and metastasis. An inverse correlation of ZBTB7A and MCAM expression in association with melanoma metastasis is further validated with data from analysis of human melanoma specimens. Implications: Together, these results uncover a previously unrecognized role of ZBTB7A in negative regulation of melanoma metastasis and have important clinical implications. Mol Cancer Res; 13(8); 1206–17. ©2015 AACR.

Personal history of gallstones and risk of incident psoriasis and psoriatic arthritis in U.S. women

Metabolic syndrome has been associated with both gallstones and psoriasis, suggesting a potential biological linkage between gallstones and psoriasis. However, the association between gallstones and psoriasis has not yet been studied.

Development of a comprehensive analytical method for furanocoumarins in grapefruit and their metabolites in plasma and urine using UPLC-MS/MS: a preliminary study

Abstract To develop a comprehensive analytical method for photoactive furanocoumarins, grapefruit (whole, flesh, peel and juice) was extracted using QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method. Seven furanocoumarins: bergaptol, psoralen, 8-methoxypsoralen, bergapten, 6′,7′-dihydroxybergamottin (6′,7′-DHB), epoxybergamottin and bergamottin were determined in grapefruit using UPLC-MS/MS. The concentrations of furanocoumarins in the plasma and urine of six healthy young adults before and after ingestion of grapefruit or grapefruit juice were also determined. Recovery rates of furanocoumarins by QuEChERS method from matrix spike sample and laboratory calibrate sample were 125.7 ± 25.4% and 105.7 ± 6.3%, respectively. Bergamottin and 6′,7′-DHB were predominant compounds in grapefruit flesh, juice and plasma, while bergaptol and 6′,7′-DHB were major compounds detected in the urine. The results demonstrated that bergamottin and 6′,7′-DHB were metabolized to bergaptol. Overall, the analytical methods developed in the present study can be applied to the analysis of various furanocoumarins in plant sources and biological samples.

Personal history of psoriasis and risk of incident cancer among women: a population-based cohort study.

DEAR EDITOR, Psoriasis is a chronic inflammatory skin disorder. The pathophysiology is characterized by T-cell-mediated keratinocytic hyperproliferation and inflammatory changes. Inflammation substantially contributes to the development and progression of cancers, with both local immune response and systemic inflammation playing dramatic roles. The chronic, inflammatory state induced by psoriasis may therefore be associated with neoplastic diseases. Most prior studies on psoriasis and cancer were based on moderate-to-severe psoriasis in clinical settings, and results for most cancers other than cutaneous squamous cell carcinoma (SCC) and Hodgkin lymphoma have been inconclusive (Appendix S1; see Supporting Information). We systematically examined the association between a personal history of psoriasis and risk of incident cancer (other than keratinocyte carcinoma, also known as nonmelanoma skin cancer, i.e. SCC and basal cell carcinoma), based on a prospective analysis of the Nurses’ Health Study (Appendix S1). In 2008 we queried Nurses’ Health Study participants as to whether they had physician-diagnosed psoriasis and if so the year of diagnosis (1997 or before, 1998–2001, 2002–5, 2006–7 or 2008). We confirmed self-reported psoriasis using the Psoriasis Screening Tool questionnaire, which was 99% sensitive and 94% specific for psoriasis in a hospitalbased pilot study. We asked about the involved body surface area (BSA) when psoriasis was at its worst, measured using the palm (i.e. the subject’s flat hand and thumb together, fingers not included). For cancer outcomes, only confirmed invasive cases after medical record review were included, except for breast cancer and bladder cancer, which included both invasive and in situ cases. Among participants with information on their history of psoriasis, we excluded cases of psoriasis that responded to the Psoriasis Screening Tool but were not verified, or cancers occurring in or before 1997 (Fig. S1; see Supporting Information). Person-years of follow-up were calculated from the return of the 1996 questionnaire to either the date of diagnosis of the first primary cancer, death, the last questionnaire response or June 2012, whichever came first. We calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) of total cancer and major individual cancers, using Cox proportional hazards models, stratified by age and 2-year interval. Details of the covariates and other statistical analysis methods are given in Appendix S1. Among a total of 64 990 participants, 2182 (3 4%) cases of psoriasis were diagnosed as of 2008, and 1404 were confirmed. Of these, 1292 (92 0%) had mild psoriasis (≤ 2 palms’ involvement). Information on psoriasis and the characteristics of the participants in 1996 is provided in Appendix S1. During the follow-up (1996–2012), 8348 cases of cancer were identified (Table 1). We did not find an altered risk of total cancer associated with personal history of psoriasis (multivariate-adjusted HR 1 02, 95% CI 0 89–1 17). In the analysis of individual cancers, personal history of psoriasis was associated with an increased risk of melanoma (HR 1 95, 95% CI 1 21–3 13) and kidney cancer (HR 2 50, 95% CI 1 27–4 92) (Table 1). We conducted additional analyses by excluding cases of self-reported psoriasis that were not reached for validation or did not respond to the validation questionnaires. The associations appeared even stronger (Table 2). Subgroup analysis by psoriasis severity found that the associations were stronger among psoriasis with ≥ 1 palm’s involvement. There was a trend towards increased risk of melanoma (Ptrend = 0 003) and kidney cancer (Ptrend < 0 001) with increasing psoriasis severity (Table 2). In the analyses excluding all cases of moderate-to-severe psoriasis (> 2 palm areas’ involvement), the associations for melanoma and kidney cancer remained significant. The HR (95% CI) was 1 98 (1 22–3 23) for melanoma and 2 44 (1 19–5 00) for kidney cancer. We conducted a set of other sensitivity analyses and secondary analyses and did not find material change of the HRs (Appendix S1). Few studies have examined the association between psoriasis and risk of incident cancer based on a population-based cohort study. Several cohort studies based on registry datasets have examined the association. Four focused on one cancer type only, and a fifth evaluated total cancer but did not examine individual cancers. The sixth and seventh studies comprehensively examined the risk of individual cancers, but both adjusted for only a few confounders. Among these studies, three examined the association for melanoma but reported opposite associations. None examined kidney cancer specifically. Comparisons of our findings with these studies are shown in Appendix S1. Inflammation and oxidative stress might be the mechanisms underlying the associations with melanoma and kidney cancer,

History of Keratinocyte Carcinoma and Risk of Melanoma: A Prospective Cohort Study

Background: The association between history of keratinocyte carcinoma (KC, also known as nonmelanoma skin cancer) and risk of developing invasive melanoma has not been assessed comprehensively using prospective data. Methods: We followed 91 846 women in the Nurses’ Health Study (NHS; 1984–2010), 114 918 women in the NHSII (1989–2011), and 48 946 men in the Health Professionals Follow-up Study (1986–2010) for diagnoses of KC and melanoma biennially. Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) of melanoma associated with history of KC, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). All statistical tests were two-sided. Results: We documented 1949 melanomas, 38 842 BCCs, and 7462 SCCs over 6.4 million person-years of follow-up. After adjustment for other risk factors, a personal history of KC was associated with an increased risk of melanoma (meta-analysis HR = 2.22, 95% CI = 1.73 to 2.85). The association was more apparent among participants with a history of both BCC and SCC (HR = 3.40, 95% CI = 1.60 to 7.19) than among participants with a history of BCC only (HR = 2.20, 95% CI = 1.80 to 2.70) or SCC only (HR = 1.56, 95% CI = 0.98 to 2.46), and there was a strong risk-increasing trend associated with a higher number of reported KCs removed by surgery (Ptrend < .001). In women, KC history was more strongly associated with head/neck melanomas (HR = 4.17, 95% CI = 2.77 to 6.27) than with trunk or limb melanomas (both HRs < 2.50, Pheterogeneity = .04). Conclusions: Our results provide novel insights for the relationship between KC history and risk of developing melanoma, which may be important for melanoma prevention.