Occupational exposure to arsenic, mercury and UV radiation and risk of melanoma: a case-control study from Italy.

BACKGROUND: Melanoma is mainly caused by sunlight radiation, but other environmental risk factors are not well known. We investigated the association between cutaneous melanoma and occupational exposure to arsenic, mercury and UV radiation. METHODS: A hospital-based case-control study was conducted in the inpatient wards of IDI-San Carlo Rome, Italy, including 304 incident cases of cutaneous melanoma and 305 frequency-matched controls. Detailed sociodemographic, clinical and host-related factors were collected, and all participants were physically examined using dermoscopy and following standard protocol for recording pigmented lesions. Four experts assessed exposure to arsenic, mercury and UV radiation based on occupational history. A multidimensional variable was created for each risk factor, by combining intensity and probability of exposure. Multivariable logistic regression models were run to calculate odds ratios (OR) and 95% confidence intervals (CI) of the association between exposure to these agents and melanoma. RESULTS: A total of 5.4% of the cases vs 2.4% of the controls were exposed to arsenic (OR = 3.12; 95% CI = 1.10-8.86 for high probability and high exposure to arsenic) after controlling for sex, age, smoking status, number of nevi, phototype and history of sunburns in childhood/adolescence. Occupational exposure to mercury and UV radiation was not associated with the risk of melanoma. CONCLUSIONS: Subjects exposed to arsenic at the workplace may be at increased risk of developing cutaneous melanoma in comparison to subjects not exposed to this agent. Further studies should be designed to investigate occupational exposure to arsenic and mercury and melanoma and confirm the findings are warranted.

Glutathione S-transferase M1 null genotype, household pesticides exposure and cutaneous melanoma.

Glutathione S-transferase (GST) activity is believed to play a critical role in cellular protection against toxic chemicals. We evaluated the role of GSTM1 polymorphisms in modifying the association between indoor pesticide exposure and cutaneous melanoma. Peripheral blood samples were collected from 325 individuals (177 patients with cutaneous melanoma and 148 controls). Genotyping was performed using the PCR method. Participants were interviewed to collect data on pesticides used indoors, sociodemographic characteristics, medical history, sun exposure and pigmented characteristics. Odds ratio and 95% confidence intervals (CIs) were calculated by unconditional logistic regression. After adjustment for sex, age, education, hair colour, skin photo-type, solar lentigines, number of nevi and sunburns episodes in childhood, a 2.76-fold (95% CI: 1.08-7.08) increase in the risk of cutaneous melanoma was observed for GSTM1 null individuals highly exposed to indoor pesticides (≥2 times/year) in comparison with GSTM1 active individuals who received low exposure (<2 times/year). Participants exposed to these products for 10 years or more and with GSTM1 null genotype also had an increased risk of cutaneous melanoma (odds ratio: 2.78; 95% CI: 1.01-7.66) in comparison with participants with a low duration of exposure (<10 years) and active GSTM1. These findings suggest that the GSTM1 null genotype is a risk modifier for cutaneous melanoma.

The protective effect of coffee consumption on cutaneous melanoma risk and the role of GSTM1 and GSTT1 polymorphisms.

PURPOSES: The authors examined the association between coffee consumption and cutaneous melanoma and the implication of GSTM1 and GSTT1 polymorphisms. METHODS: A hospital-based case-control study was conducted in the inpatient wards of IDI-San Carlo Rome, Italy, including 304 incident cases of cutaneous melanoma and 305 controls. Information on socio-demographic characteristics, medical history, smoking, sun exposure, pigmentary characteristics and diet was collected for all subjects. Within the study, individual patterns at two polymorphic genes (GSTM1 and GSTT1) belonging to glutathione S-transferases family were investigated in 188 cases of cutaneous melanoma and 152 controls. Logistic regression was the method used to estimate odds ratio and 95 % confidence intervals. RESULTS: High frequency of coffee drinking (>once daily), compared with low-frequency consumption of coffee (≤7 times weekly) was associated with a protective effect for cutaneous melanoma (OR 0.46; 95 % CI 0.31-0.68) after adjusting for sex, age, education, hair colour, common nevi, skin phototype, and sunburn episodes in childhood. When stratified by GSTM1 and GSTT1 genotype, the protective effect of coffee was extremely high for subjects with both GSTM1 and GSTT1 null polymorphisms (OR 0.01; 95 % CI 0.0003-0.54). CONCLUSIONS: Our results show a protective effect of coffee consumption for cutaneous melanoma, in particular for those with homozygous deletion for GSTM1 and GSTT1.

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.

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.

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.