Polymorphisms of GSTM1 and GSTT1, sun exposure and the risk of melanoma: a case-control study.

Glutathione S-transferases (GSTs) are a family of enzymes that are known to play an important role in cellular protection against oxidative stress, including the oxidative stress caused by ultraviolet radiation. This study focused on the possible involvement of GSTM1 and GSTT1 polymorphisms in risk modulation of cutaneous melanoma. Within a case-control study, the presence of the null polymorphism at GSTM1 and GSTT1 was investigated in 188 cases of cutaneous melanoma and 152 controls. Information on socio-demographic characteristics, medical history, sun exposure and pigmentary characteristics were collected for all subjects. Logistic regression was used to estimate odds ratio (OR) and 95% confidence intervals (CI). An interaction was suggested between the GSTM1 and GSTT1 "null" genotype and episodes of sunburn in childhood OR of interaction (1.65, 95% CI (95% CI) 0.27-9.94). The risk of melanoma among the subset of participants who reported sunburns in childhood and who had both null variants, was nine (OR 9.16; 95% CI 1.18-70.9). The results suggest that subjects carrying both GSTM1 and GSTT1 null polymorphisms and experiencing sunburns in childhood have an extremely high risk of melanoma.

The association between residential pesticide use and cutaneous melanoma.

Occupational pesticide exposure has been linked to cutaneous melanoma in epidemiological studies. We studied the association between cutaneous melanoma and the residential use of pesticides. This is a case-control study of cutaneous melanoma (287 incident cases; 299 controls). Data on pesticide use was obtained with a standardised interview. An increased risk of melanoma was found for high use (4 times annually) of indoor pesticides (odds ratio (OR)=2.18; 95% confidence intervals (CI) 1.07-4.43) compared to low use (1 times annually), after adjustment for sex, age, education, sun exposure and pigmentary characteristics. Subjects exposed for 10 years or more had two and a half times the risk (OR=2.46; 95% CI 1.23-4.94) of those exposed for less than 10 years. A dose response was observed for the intensity of pesticides use (p(trend)=0.027). The results indicate that residential pesticide exposure may be an independent risk factor for cutaneous melanoma.

Survival and prognostic variables of cutaneous melanoma observed between 1995 and 2000 at Istituto Dermopatico Dell'Immacolata (IDI-IRCCS), Rome, Italy.

INTRODUCTION: Melanoma is an increasingly common malignancy of melanocytes, with incidence rates steadily rising over the past several decades. The objective of this study was to evaluate 5-year survival and to investigate the association between melanoma mortality and clinical and histological features. METHODS: We conducted a 5-year cohort study among 1020 patients from the same geographic area (Rome) with a single primary cutaneous melanoma diagnosed between January 1995 and December 2000. Survival probability was determined by Kaplan-Meier estimates, and prognostic factors were evaluated by multivariate analysis (Cox proportional hazards model). RESULTS: Survival decreased with increasing age (P for trend <0.049) and Breslow thickness (P for trend <0.0001). In the multivariate Cox model, Breslow thickness was the only independent prognostic factor for mortality in primary melanoma patients. The risk of death among patients with melanoma increased with increasing tumour thickness 0.76-1.49 mm (relative risk (RR) 2.67, 95% confidence interval (95% CI) 0.63-11.4); 1.50-4.0 mm (RR 6.38, 95% CI 1.75-23.2), >4.0 mm (RR 34.6, 95% CI 8.23-145.7) (P for trend <0.0001). The Years of Life Lost (YLLs) for the Breslow categories < or =0.75 mm, 0.76-1.49 mm, 1.50-4.0 mm and >4.0 mm were 65.4, 153.6, 274.3 and 317.6 years, respectively. CONCLUSION: This study shows the great importance of secondary melanoma prevention and illustrates how many years of life could be saved by early diagnosis.

Relationship between smoking and the clinical severity of psoriasis.

OBJECTIVE: To evaluate the association between different components of smoking history and the clinical severity of psoriasis. DESIGN: A hospital-based cross-sectional study. SETTING: Inpatient wards of a hospital for skin diseases in Rome, Italy. PATIENTS: A total of 818 adults with psoriasis. MAIN OUTCOME MEASURE: The Psoriasis Area and Severity Index was used to assess the clinical severity of psoriasis between February 21, 2000, and February 19, 2002. RESULTS: After adjustment for potential confounders (sex, age, body mass index, psychological distress, family history of psoriasis, duration of psoriasis disease, and alcohol consumption), high intensity of smoking (>20 cigarettes daily) vs a lower level of consumption (< or =10 cigarettes daily) was associated with a more than 2-fold increased risk of clinically more severe psoriasis (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.2-4.1). Cigarette-years, measured as the product of the intensity and duration (years) of smoking, significantly increased the risk of clinically more severe psoriasis after adjustment for confounding factors (OR,1.3; 95% CI, 1.0-1.6, for a 600-U increase in cigarette-years). Separate analyses for men and women showed that the effect of cigarette-years was stronger for women (OR, 1.8; 95% CI, 1.2-2.6, for a 400-U increase in cigarette-years) than for men (OR, 1.2; 95% CI, 0.9-1.6, for a 700-U increase in cigarette-years). CONCLUSION: Smoking is associated with the clinical severity of psoriasis and highlights the importance of smoking cessation in patients with psoriasis.

A melanoma risk score in a Brazilian population.

BACKGROUND: Important risk factors for cutaneous melanoma (CM) are recognized, but standardized scores for individual assessment must still be developed. OBJECTIVES: The objective of this study was to develop a risk score of CM for a Brazilian sample. METHODS: To verify the estimates of the main risk factors for melanoma, derived from a meta-analysis (Italian-based study), and externally validate them in a population in southern Brazil by means of a case-control study. A total of 117 individuals were evaluated. Different models were constructed combining the summary coefficients of different risk factors, derived from the meta-analysis, multiplied by the corresponding category of each variable for each participant according to a mathematical expression. RESULTS: the variable that best predicted the risk of CM in the studied population was hair color (AUC: 0.71; 95% CI: 0.62-0.79). Other important factors were freckles, sunburn episodes, and skin and eye color. Consideration of other variables such as common nevi, elastosis, family history, and premalignant lesions did not improve the predictive ability of the models. CONCLUSION: The discriminating capacity of the proposed model proved to be superior or comparable to that of previous risk models proposed for CM.

Identifying individuals at high risk of melanoma: a simple tool.

Simple and reliable tools for identifying patients at high risk for melanoma with preventive measures have important public health implications. An individual risk score for cutaneous melanoma was constructed and externally validated. With the summary coefficients of the risk factors for cutaneous melanoma, derived from a meta-analysis, a melanoma risk score was tested in an Italian population and externally validated in a Brazilian population. Common nevi, skin and hair color, freckles, and sunburns in childhood were the variables included in the final predictive model. The discriminatory ability of the models was assessed by the receiver operating characteristic (ROC) curve. The performance of the model was also evaluated by conducting an external validation. The area under the curve (AUC) of the candidate model was 0.79 (95% confidence interval: 0.75-0.82). The same model, when applied in the Brazilian population, presented an AUC of 0.79 (95% confidence interval: 0.70-0.86). At the cut-off level of 3 and more, 89 and 80% of the melanoma cases were correctly classified as 'at risk for melanoma' in the Italian and in the Brazilian populations, respectively. The risk model is a simple tool that identifies patients for preventive measures and may be used with reasonable confidence in different populations. The risk model may help family doctors in referring patients to dermatological clinics and thus improve early diagnosis.

A melanoma risk score in a Brazilian population / Um escore de risco para melanoma em uma população brasileira

BACKGROUND: Important risk factors for cutaneous melanoma (CM) are recognized, but standardized scores for individual assessment must still be developed. OBJECTIVES: The objective of this study was to develop a risk score of CM for a Brazilian sample. METHODS: To verify the estimates of the main risk factors for melanoma, derived from a meta-analysis (Italian-based study), and externally validate them in a population in southern Brazil by means of a case-control study. A total of 117 individuals were evaluated. Different models were constructed combining the summary coefficients of different risk factors, derived from the meta-analysis, multiplied by the corresponding category of each variable for each participant according to a mathematical expression. RESULTS: the variable that best predicted the risk of CM in the studied population was hair color (AUC: 0.71; 95% CI: 0.62-0.79). Other important factors were freckles, sunburn episodes, and skin and eye color. Consideration of other variables such as common nevi, elastosis, family history, and premalignant lesions did not improve the predictive ability of the models. CONCLUSION: The discriminating capacity of the proposed model proved to be superior or comparable to that of previous risk models proposed for CM. .

FUNDAMENTOS: importantes fatores de risco para melanoma cutâneo são reconhecidos, mas escores padronizados para avaliação individual ainda precisam ser elaborados. OBJETIVOS: o objetivo deste estudo foi desenvolver um escore de risco de melanoma cutâneo para uma amostra brasileira. MÉTODOS: verificar as estimativas dos principais fatores de risco para melanoma, derivado de uma meta-análise (estudo de base italiano) e, externamente, validar em uma população do sul do Brasil por um estudo caso-controle. Um total de 117 indivíduos foram avaliados. RESULTADOS: a variável com maior poder preditivo para o risco de melanoma cutâneo na população estudada foi a cor do cabelo (AUC: 0,71, IC 95%: 0,62-0,79). Outros fatores importantes para o modelo foram: sardas, queimaduras solares, e cor de pele e cor dos olhos. Adicionando outras variáveis, como os nevos comuns, elastose, história familiar e lesões pré-malignas não houve melhora da capacidade preditiva. CONCLUSÃO: A capacidade discriminatória do modelo proposto mostrou-se superior ou comparável aos modelos de risco anteriores propostos para melanoma cutâneo. .