Statins may reduce disease recurrence in patients with ulcerated primary melanoma.

BACKGROUND: Statins may restrict the cellular functions required for melanoma growth and metastasis. OBJECTIVES: To determine whether long-term statin use commenced before diagnosis of a primary melanoma is associated with reduced risk of melanoma recurrence. METHODS: We prospectively followed a cohort of patients newly diagnosed between 2010 and 2014 with localized tumour-stage T1b to T4b melanoma in Queensland, Australia. We used Cox regression analyses to examine associations between long-term statin use and melanoma recurrence for the entire cohort, and then separately by sex and by presence of ulceration, due to evidence of effect modification. RESULTS: Among 700 patients diagnosed with stage T1b to T4b primary melanoma (mean age 62 years, 59% male, 28% with ulcerated tumours), 94 patients (13%) developed melanoma recurrence within 2 years. Long-term statin users (n = 204, 29%) had a significantly lower risk of disease recurrence than nonusers [adjusted hazard ratio (HRadj ) 0·55, 95% confidence Interval (CI) 0·32-0·97] regardless of statin subtype or potency. Compared with nonusers of statins, risk of recurrence was significantly decreased in male statin users (HRadj 0·39, 95% CI 0·19-0·79) but not in female statin users (HRadj 0·82, 95% CI 0·29-2·27) and in statin users with ulcerated (HRadj 0·17, 95% CI 0·05-0·52) but not nonulcerated (HRadj 0·91, 95% CI 0·46-1·81) primary melanoma. CONCLUSIONS: Statins commenced before melanoma diagnosis may reduce the risk of melanoma recurrence, especially in men and in those with ulcerated tumours. Clinical trial evaluation of the potential role of statins in improving the prognosis of high-risk melanoma is warranted.

Reproductive factors and risk of melanoma: a population-based cohort study.

BACKGROUND: The association between reproductive factors and risk of cutaneous melanoma (CM) is unclear. We investigated this issue in the Norwegian Women and Cancer cohort study. OBJECTIVES: To examine the association between the reproductive factors age at menarche, menstrual cycle length, parity, age at first and last birth, menopausal status, breastfeeding duration and length of ovulatory life, and CM risk, overall and by histological subtypes and anatomical site. METHODS: We followed 165 712 women aged 30-75 years at inclusion from 1991-2007 to the end of 2015. Multivariable Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: The mean age at cohort enrolment was 49 years. During a median follow-up of 18 years, 1347 cases of CM were identified. No reproductive factors were clearly associated with CM risk. When stratifying by histological subtype we observed significant heterogeneity (P = 0·01) in the effect of length of ovulatory life on the risk of superficial spreading melanoma (HR 1·02, 95% CI 1·01-1·04 per year increase) and nodular melanoma (HR 0·97, 95% CI 0·94-1·01 per year increase). When stratifying by anatomical site, menopausal status (HR 0·54, 95% CI 0·31-0·92, postmenopausal vs. premenopausal) and menstrual cycle length (HR 1·07, 95% CI 1·01-1·13, per day increase) were associated with CM of the trunk, and significant heterogeneity between anatomical sites was observed for menopausal status (P = 0·04). CONCLUSIONS: In this large population-based Norwegian cohort study, we did not find convincing evidence of an association between reproductive factors and risk of CM.

Anthropometric factors and Breslow thickness: prospective data on 2570 cases of cutaneous melanoma in the population-based Janus Cohort.

BACKGROUND: Breslow thickness is the most important prognostic factor of localized cutaneous melanoma (CM), but associations with anthropometric factors have been sparsely and incompletely investigated. OBJECTIVES: To examine prediagnostic body mass index (BMI), body surface area (BSA), and height, weight and weight change in relation to Breslow thickness, overall and by anatomical site and histological subtype; and to assess possible nonlinear associations between these anthropometric factors and Breslow thickness. METHODS: CMs in the Janus Cohort were identified between 1972 and 2014. Linear regression was used to estimate geometric mean ratios (GMRs) of Breslow thickness with 95% confidence intervals (CIs) according to anthropometric factors. Restricted cubic splines in generalized linear models predicted adjusted mean Breslow thickness, and were used to assess possible nonlinear relationships. RESULTS: Of 2570 cases of CM, obese patients had a GMR of 1·16 (95% CI 1·04-1·30) of Breslow thickness vs. normal-weight patients. For BSA and weight, quintile 5 showed GMRs of 1·13 (95% CI 1·00-1·27) and 1·17 (95% CI 1·03-1·33) of Breslow thickness vs. quintile 1, respectively. Associations seemed restricted to superficial spreading melanomas and CMs on the trunk and lower limbs. The associations plateaued at an adjusted mean Breslow thickness of about 2·5 mm (BMI 29 kg m-2 , BSA 2·05 m2 and weight 90 kg), before declining for the highest values. No associations were found for height and weight change. CONCLUSIONS: This large case-series of incident CM demonstrated positive associations between BMI, BSA, weight and Breslow thickness, and suggested that behavioural or other mechanisms apply at high values.

The association between circulating fetuin-A levels and type 2 diabetes mellitus risk: systematic review and meta-analysis of observational studies.

BACKGROUND AND OBJECTIVE: Fetuin-A is a liver-derived circulating protein that is associated with insulin resistance and diabetes. The objective of this systematic review and meta-analysis of published observational studies was to investigate mean levels of fetuin-A in T2D patients and the relationship between blood fetuin-A levels and T2D risk. MATERIALS AND METHODS: PubMed, Embase, Google Scholar, Web of Science, and The Cochrane Library were systematically searched for potential relevant studies up to 1 December 2016. Natural logarithm-transformed estimate risks, standard mean differences on the basis of Hedges's adjusted g, and 95% confidence intervals (CIs) were calculated for all eligible studies and were combined to measure the pooled data using random-effects model. RESULTS: A total of 32 studies including 27 case-control and 5 cohort studies were included in the current study. Fetuin-A levels in T2D patients were significantly higher than control groups [Hedges' g = 1.73, 95% CI (1.25-2.22), P < 0.001], with significant heterogeneity across studies (P < 0.001, I 2 = 98.46%). Findings from meta-analyses of cohort studies showed a statistically significant association between fetuin-A levels and T2D risk [rate ratio = 1.62, 95% CI (1.26-2.08), P < 0.001], with no significant heterogeneity (P = 0.10, I 2 = 46.06%). CONCLUSION: We found a significant relationship between the fetuin-A levels with T2D risk. Although fetuin-A may be as a potential screening and prediction biomarker or a therapeutic target in T2D patients, further studies are required in this regard.

The Effect of n-3 Polyunsaturated Fatty Acid Supplementation on Androgen Status in Patients with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Clinical Trials.

The anti-androgenic role of n-3 polyunsaturated fatty acids (PUFAs) among patients with polycystic ovary syndrome (PCOS) has recently been proposed. The present study aimed to systematically review clinical trials assessing the effects of n-3 PUFAs consumption on androgen status among adult females with PCOS. PubMed, ISI Web of Science, Google Scholar, and Scopus were searched up to December 2015. Clinical investigations assessing the effect of n-3 PUFAs on adult females with PCOS were included. Mean±standard deviation of change in serum total testosterone, sex hormone binding globulin (SHBG), and dehydroepiandrostrone sulfate (DHEAS) were extracted. Eight clinical trials with 298 participants were eligible. Meta-analysis showed that n-3 PUFAs supplementation marginally reduces total testosterone (mean difference [MD]: - 0.19 nmol/l; 95% CI: - 0.39 to 0.00; p=0.054), but not SHBG (MD: 1.75 nmol/l; 95% CI: -0.51 to 4.01; p=0.129) or serum DHEAS levels (Hedes' g: -0.11 nmol/l; 95% CI: -0.29 to 0.06; p=0.19) among adult females with PCOS. Subgroup analyses showed that only before-after studies (Hedges' g: 0.15; 95% CI: -0.27 to -0.04; p=0.01) and long-term interventions (>6 weeks) (Hedges' g: -0.17; 95% CI, -0.29 to -0.05; p=0.004) had reducing effects on serum DHEAS levels. The majority of long-term trials utilized a single group design (no control group). It does not appear that n-3 PUFAs supplementation significantly affects the androgenic profile of females with PCOS; however, some before-after and long-term intervention studies show reduced DHEAS levels. Future studies incorporating double blinded placebo controlled clinical trials with long follow-up periods are warranted.

Prevalence and trends of sunscreen use and sunburn among Norwegian women.

BACKGROUND: Sunscreen is recommended to prevent sunburn and skin cancer. OBJECTIVES: To investigate sunscreen use in relation to demographic and phenotypic characteristics among women in Norway, as well as solar UV exposure, sunburn experience in different decades of life, and temporal trends in sunscreen use. METHODS: We used data from the Norwegian Women and Cancer Study, a large population-based prospective cohort study. Log-binomial regression was used to estimate the association between sunscreen use and personal characteristics. Results are presented as prevalence ratios (PRs) and 99% confidence intervals (CIs). RESULTS: The study sample consisted of 148,869 women, with a mean age, when answering the questionnaire, of 53 years (range 41-75). Sixty-five per cent of the women used sunscreen during the Easter holiday, 73% in northern latitudes and 87% in bathing vacations in southern latitudes. Sunscreen with sun protection factor (SPF) ≥ 15 was used by 25,156 (18%) at Easter, 18,118 (13%) in northern latitudes and 22,678 (30%) in southern latitudes. The prevalence of sunscreen use increased from 1997 to 2007, and this increase was associated with age. In 1997, 39% of women reported at least one sunburn per year in the recent decade, compared with 46% in 2007 (Ptrend = 0·001). Women who experienced at least four sunburns per year during adolescence reported more sunscreen use in adulthood (PREaster 1·54, 99% CI 1·30-1·83; PRnorthern latitudes 1·49, 99% CI 1·20-1·84; PRsouthern latitudes 1·37, 99% CI 1·14-1·65). CONCLUSIONS: The prevalence of sunscreen use increased from 1997 to 2007. However, this increase has not been accompanied by a decrease in sunburn. Moreover, use of sunscreen with the recommended SPF was not common among Norwegian women.

Effect of eicosapentaenoic Acid (EPA) and vitamin e on the blood levels of inflammatory markers, antioxidant enzymes, and lipid peroxidation in Iranian basketball players.

BACKGROUND: Exercise can change the release of numerous cytokines and modulate their receptor systems. Dietary ω-3 lipids may decrease the levels of inflammatory cytokines and prostaglandins (PGs). Therefore, in this study, we investigated the effects of exercise and eicosapentaenoic acid (EPA) supplementation, with or without vitamin E, on the blood levels of IL-2, TNF-α, catalase, glutathione reductase, and MDA in male basketball players. METHODS: Thirty-four well-trained male basketball players were enrolled into the study. Venous blood samples were obtained from all subjects between 5:00 and 6:00 p.m., after intensive endurance exercising for 2 hours, at the baseline and after intervention. Subjects received 2g EPA and/or 400 IU vitamin E or placebo depends on their groups for 6 weeks. RESULTS: There were significant fall (paired t-test) in TNF-α in group1(P< 0.05), and in MDA in group 3 (P<0.05), whereas there were significant increase in glutathione reductase in groups1 and 3 (P< 0.05), and in MDA in group2 (P< 0.05).There were significant differences (Tukey) in glutathione reductase between groups 2 and 3 (P< 0.05), and in IL-2 between groups 1 and other groups (P< 0.01), but there were no significant differences in MDA, CAT, and TNF-α, among groups after 6 week of intervention. CONCLUSION: Six weeks of EPA+vitamin E supplementation enhances the plasma levels of IL-2 and erythrocytes glutathione reductase, whereas it reduces TNF-α, and 6 weeks of EPA supplementation alone enhances only the serum level of MDA.

Prevalence of classical phenylketonuria in mentally retarded individuals in Iran.

Using Guthrie Biological Inhibition Assay, 4963 mentally retarded individuals housed in 31 cities and towns across the country were screened for PKU. The average prevalence of classical PKU in the study population was 2.1%, which is higher than that reported for most mentally retarded populations in other countries prior to the implementation of a nationwide newborn screening programme for PKU. The prevalence of PKU in 1814 mentally retarded inmates housed in shelters in Tehran was 2.81%, and the prevalence of the disease in 3149 inmates sheltered in other cities and towns was 1.68%. It appears that most of the difference between the prevalence of PKU in these two populations is due to a unique PKU referral pattern in Iran. The high prevalence of PKU in the mentally retarded population in Iran could be indicative of a high incidence of the disease among Iranian neonates. This in turn appears to be positively influenced by both a high frequency of the PKU allele and a high rate of consanguinity in the country. Our finding suggests that instead of limited local screening programmes in the country, a nationwide screening programme for PKU, especially if coupled with screening for congenital hypothyroidism, would be highly cost-effective and warranted.