WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , کتابخانه مرکزی دانشگاه علوم پزشکی تهران

WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues

Once foods in the United States were fortified with vitamin D, rickets appeared to have been conquered, and many considered major health problems from vitamin D deficiency resolved. But vitamin D deficiency is common. This review considers the role of vitamin D in skeletal and nonskeletal health and suggests strategies for the prevention and treatment of vitamin D deficiency.

Vitamin D Deficiency

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

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Integrative analysis of 111 reference human epigenomes

admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER

Vitamin D deficiency.

There is persuasive evidence that each of the three main types of skin cancer, basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma, is caused by sun exposure. The incidence rate of each is higher in fairer skinned, sun-sensitive rather than darker skinned, less sun-sensitive people; risk increases with increasing ambient solar radiation; the highest densities are on the most sun exposed parts of the body and the lowest on the least exposed; and they are associated in individuals with total (mainly SCC), occupational (mainly SCC) and non-occupational or recreational sun exposure (mainly melanoma and BCC) and a history of sunburn and presence of benign sun damage in the skin. That UV radiation specifically causes these skin cancers depends on indirect inferences from the action spectrum of solar radiation for skin cancer from studies in animals and the action spectrum for dipyrimidine dimers and evidence that presumed causative mutations for skin cancer arise most commonly at dipyrimidine sites. Sun protection is essential if skin cancer incidence is to be reduced. The epidemiological data suggest that in implementing sun protection an increase in intermittency of exposure should be avoided, that sun protection will have the greatest impact if achieved as early as possible in life and that it will probably have an impact later in life, especially in those who had high childhood exposure to solar radiation.

The epidemiology of UV induced skin cancer.

Estimates have been made of the proportion of cutaneous malignant melanomas caused by sun exposure by comparing the observed incidence of melanoma with estimates of the incidence in the absence of sun exposure. The estimated proportions varied from 0.97 in males and 0.96 in females in Queensland, Australia, when the incidence on the whole body was compared with that on unexposed sites, to 0.68 when incidence in people born in Australia was compared with that in migrants to Australia from areas of lower sun exposure. A comparison of US Whites and US Blacks, in which the incidence in Blacks was taken as the incidence in unexposed Whites, gave estimates of 0.96 in males and 0.92 in females. It was estimated that some 59,000 (65%) of about 92,000 melanomas that occurred worldwide in 1985 were caused by sun exposure. This is probably a minimum estimate. That 20% of the world's melanomas are estimated to occur in Black African and Asian populations and are of unknown cause would justify studies of the causes of melanoma in these populations.

How much melanoma is caused by sun exposure

BackgroundNonmelanoma skin cancers, such as basal-cell carcinoma and squamous-cell carcinoma, are common cancers that are caused principally by ultraviolet (UV) radiation. Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses. MethodsIn this phase 3, double-blind, randomized, controlled trial, we randomly assigned, in a 1:1 ratio, 386 participants who had had at least two nonmelanoma skin cancers in the previous 5 years to receive 500 mg of nicotinamide twice daily or placebo for 12 months. Participants were evaluated by dermatologists at 3-month intervals for 18 months. The primary end point was the number of new nonmelanoma skin cancers (i.e., basal-cell carcinomas plus squamous-cell carcinomas) during the 12-month intervention period. Secondary end points included the number of new squamous-cell carcinomas and basal-cell carcinomas and the number of actinic keratoses during the 12-month inte...

A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention

Background: Melanoma incidence and survival are positively associated, both geographically and temporally. Solar elastosis, a histologic indicator of cutaneous sun damage, has also been positively associated with melanoma survival. Although these observations raise the possibility that sun exposure increases melanoma survival, they could be explained by an association between incidence and early detection of melanoma. We therefore evaluated the association between measures of skin screening and death from cutaneous melanoma. Methods: Case subjects (n = 528) from a population-based study of cutaneous melanoma were followed for an average of more than 5 years. Data, including measures of intermittent sun exposure, perceived awareness of the skin, skin selfscreening, and physician screening, were collected during in-person interviews and review of histopathology and histologic parameters (i.e., solar elastosis, Breslow thickness, and mitoses) for all of the lesions. Competing risk models were used to compute risk of death (hazard ratios [HRs], with 95% confi dence intervals [CIs]) from melanoma. All statistical tests were two-sided. Results: Sunburn, high intermittent sun exposure, skin awareness histories, and solar elastosis were statistically signifi cantly inversely associated with death from melanoma. Melanoma thickness, mitoses, ulceration, and anatomic location on the head and neck were statistically signifi cantly positively associated with melanoma death. In a multivariable competing risk analysis, skin awareness (with versus without, HR = 0.5, 95% CI = 0.3 to 0.9, P = .022) and solar elastosis (present versus absent, HR = 0.4, 95% CI = 0.2 to 0.8, P = .009) were strongly and independently associated with melanoma death after adjusting for Breslow thickness, mitotic index, and head and neck location, which were also independently associated with death. Conclusions: Sun exposure is associated with increased survival from melanoma. [J Natl Cancer Inst 2005;97:195 – 9]

Sun Exposure and Mortality From Melanoma

Epidemiologic evidence on the relation between sunlight and cancer is reviewed. Strong evidence implicates sunlight as a cause of skin cancer, although, for melanoma and basal cell carcinoma, the relationship is complex. Both types of cancer are associated more strongly with nonoccupational exposure than with occupational exposure, and the pattern and amount of exposure each appear to be important. Squamous cell carcinoma appears to be related more strongly to total (i.e., both occupational and nonoccupational) exposure to the sun. The evidence that sunlight causes melanoma of the eye is weak. It shows no latitude gradient and the results of case-control studies are conflicting. There is inadequate evidence to suggest that sunlight does or does not cause any other type of cancer.

Anne Kricker

Papers

The epidemiology of UV induced skin cancer.

How much melanoma is caused by sun exposure

A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention

Sun Exposure and Mortality From Melanoma

Sunlight and cancer