In vivo Raman spectroscopic characteristics of different sites of the oral mucosa in healthy volunteers.

OBJECTIVES: Investigate the biochemistry of in vivo healthy oral tissues through Raman spectroscopy. We aimed to characterize the biochemical features of healthy condition in oral subsites (buccal mucosa, lip, tongue, and gingiva) of healthy subjects. More specifically, we investigated Raman spectral characteristics and biochemical content of in vivo healthy tissues on Brazilian population. This characterization can be used to better define normal tissue and improve the detection of oral premalignant conditions in future studies. MATERIALS AND METHODS: For spectroscopic analysis a Raman spectrometer (Kaiser Optical Systems imaging spectrograph Holospec, f / 1.8i-NIR) coupled with a laser 785 nm, 60 mW was used. Raman measurements were obtained by means of an optical fiber (EMVision fiber optic probe) coupled between the laser and the spectrometer. Three spectra per site were acquired from the lip, buccal mucosa, tongue, and gingiva of ten healthy volunteers. This resulted in 30 spectra per oral sub-site and in total 120 spectra. RESULTS: We report detailed biochemical information on these subsites and their relative composition based on deconvolution studies of their spectra. Finally, we also report classification efficiency of 61, 83, 41, and 93% for buccal, gingiva, lip, and tongue respectively after applying multivariate statistical tools. CONCLUSIONS: We quantitated the contribution of various biochemicals in terms of percentage, and this will enable comparison not only across anatomical sites but also across studies. Raman spectroscopy can rapidly probe tissue biochemistry of healthy oral regions. Moreover, the study suggests the possibility of using Raman spectroscopy combined with signal processing and multivariate analysis methods to differentiate the oral sites in healthy conditions and compare with pathological conditions in future studies. CLINICAL RELEVANCE: The spectral characterization of the healthy condition of oral tissues by a noninvasive, label-free, and real-time analytical techniques is important to create a spectral reference for future diagnosis of pathological conditions.

Position statement for the management of comorbidities in psoriasis.

BACKGROUND: The association between psoriasis and some diseases has become relevant in recent years. Providing appropriate management of psoriasis from an early stage requires prompt diagnosis and treatment of concomitant diseases and to prevent any potential comorbidity. This approach should consider the adverse events of the drugs used to treat psoriasis potentially related to the onset of comorbidities. OBJECTIVE: To provide the dermatologist with an accurate and friendly tool for systematizing the diagnosis of psoriasis-associated comorbidities, which generally escapes the scope of the dermatology setting, and to facilitate decision-making about the referral and treatment of patients with comorbidities. METHODS: These position statement recommendations were developed by a working group composed of ten experts (four dermatologists, one cardiologist, one rheumatologist, one gastroenterologist, one nephrologist, one endocrinologist and one psychiatrist) and two health services researchers. The expert group selected the psoriasis comorbidities considered according to their relevance in the dermatology setting. The recommendations on diagnostic criteria are based on the current clinical practice guidelines for each of the comorbidities. The information regarding the repercussion of psoriasis medical treatments on associated comorbid diseases was obtained from the summary of product characteristics of each drug. RESULTS: Recommendations were developed to detect and refer the following psoriasis comorbidities: psoriatic arthritis, cardiovascular risk factors (diabetes, dyslipidaemia, obesity, hypertension and metabolic syndrome), non-alcoholic fatty liver disease, inflammatory bowel disease, kidney disease and psychological disorders (anxiety and depression). In addition, alcohol consumption and tobacco consumption were included. The tables and figures are precise, easy-to-use tools to systematize the diagnosis of comorbidities in patients with psoriasis and facilitate the decision-making process regarding referral and treatment of patients with an associated disease. CONCLUSION: The application of these position statement recommendations will facilitate the dermatologist practice, and benefit psoriasis patients' health and quality of life.

Recommendations for the management of comorbidity in hidradenitis suppurativa.

BACKGROUND: The association between hidradenitis suppurativa (HS) and some diseases is becoming relevant in recent years. Providing appropriate management of HS from an early stage requires to include prompt diagnosis and treatment of concomitant diseases and to prevent any potential comorbidity. This approach should consider the adverse events of the drugs used to treat HS potentially related to the onset of a comorbidity. OBJECTIVE: To provide the dermatologist with an accurate, easily used tool that will inform the diagnosis of HS comorbidity, and to facilitate decision-making regarding the referral and treatment of patient with HS-associated comorbidity. METHODS: These recommendations have been developed by a working group composed of seven experts (three dermatologists, a cardiovascular specialist internist, a rheumatologist expert in spondyloarthritis, a gastroenterologist and a psychiatrist) and a team of three methodologist researchers. The expert group selected the HS comorbidities considered in these recommendations through a literature review. The recommendations on diagnostic criteria are based on the relevant clinical practice guidelines for each of the comorbidities and on the recommendations of the experts. The information regarding the repercussion of HS medical treatments on associated comorbid diseases was obtained from the summary of product characteristics of each drug. RESULTS: The comorbidities considered in this guide are as follows: cardiovascular risk factors (diabetes, dyslipidaemia, obesity, hypertension and metabolic syndrome), inflammatory bowel disease, inflammatory joint disorders and psychological disorders (anxiety and depression). In addition, the association between HS and the consumption of alcohol and tobacco is included. The tables and figures are a precise, easy-to-use tool to systematize the diagnosis of comorbidity in patients with HS and facilitate the decision-making process regarding referral and treatment of patients with an associated disease. CONCLUSION: The application of these recommendations will facilitate the dermatologist practice and benefit HS patients' health and quality of life.

The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm.

The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.

Implant-abutment connections: influence of the design on the microgap and their fatigue and fracture behavior of dental implants.

Microgap between implant and abutment can produce biological and mechanical problems such as peri-implantitis and/or fatigue failures. The aim of this study was to evaluate microgap size and fatigue behavior of external and internal connections. In both systems the torque to tighten the abutment screw of single crown abutments was 45 Ncm. Fifty implants for each connection type were studied. One subgroup (n = 5) was used by the observation and evaluation of the microgap, other (n = 5) was tested for fracture strength and the other (n = 40) was subjected to dynamic loading. The internal connection presents a lower microgap than the external ones. From fatigue results, the external hexagon interface showed superior result compared to the internal hexagon interfaces. The tolerances in the internal connections are better and favour the fatigue behavior but this factor alone is not sufficient to improve the fatigue response in relation to the external connections when the screw is subjected at the same torque. The external system presents a higher value of the area than the internal and it produces a better load distribution. Microgaps and mechanical properties are very important for the long-term behavior of the dental implants and these aspects should be known by the implantologists.

Comparative analysis of 2 resonance frequency measurement devices: Osstell Mentor and Osstell ISQ.

OBJECTIVE: Comparing reliability of Osstell Mentor and Osstell ISQ in implant stability measurement, and assessing whether their measurements are comparable. MATERIALS AND METHOD: Implant stability was measured with both devices on 58 implants in 15 patients. Six measurements were completed with each device with 2 different transducers (3 measurements with each transducer), that is, 12 measurements for each implant. RESULTS: Mean implant stability quotient (ISQ) value with Osstell ISQ was 72.59, 72.47, and 73.17 in the first measurements, respectively. With Osstell Mentor, the results were 72.43, 72.60, and 73.26, respectively; mean ranges were 3.37, 3.60, and 3.75, respectively. However, mean value with Osstell ISQ and Osstell Mentor was 72.87 and 72.04, respectively. The intraclass correlation coefficient was 0.98. This means an almost perfect degree of concordance between both devices. CONCLUSIONS: Resonance frequency analysis systems in Osstell Mentor and Osstell ISQ show almost perfect reproducibility and repeatability.

Recommendations for the coordinated management of psoriatic arthritis by rheumatologists and dermatologists: a Delphi study.

Psoriatic arthritis, a chronic inflammatory musculoskeletal disease that is associated with psoriasis, causes joint erosions, accompanied by loss of function and quality-of-life. The clinical presentation is variable, with extreme phenotypes that can mimic rheumatoid arthritis or ankylosing spondylitis. Because psoriasis usually presents before psoriatic arthritis, the dermatologist plays a key role in early detection of the latter. As many treatments used in psoriasis are also used in psoriatic arthritis, treatment recommendations should take into consideration the type and severity of both conditions. This consensus paper presents guidelines for the coordinated management of psoriatic arthritis by rheumatologists and dermatologists. The paper was drafted by a multidisciplinary group (6rheumatologists, 6dermatologists, and 2epidemiologists) using the Delphi method and contains recommendations, tables, and algorithms for the diagnosis, referral, and treatment of patients with psoriatic arthritis.

Perception of patients with retinal pathology on aspects of visual function and their management.

BACKGROUND AND OBJECTIVE: Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are highly prevalent. OBJECTIVE: To explore perceptions of patients with AMD or DR about the impact of the disease and treatment on their daily living activities. MATERIALS AND METHODS: Semi-structured interviews with a questionnaire developed from validated patient reported outcomes questionnaires. The questionnaire consisted of 19 questions about the disease and 9 about the treatment. The questions (items) were answered on a scale from 1 to 9. In addition, the patient interviewed was invited to make free comments on each question. Nine patients with AMD and 9 with DR were interviewed by videoconference or telephone call. A quantitative analysis of the responses and a qualitative analysis of the comments were carried out. RESULTS: The most relevant item for patients with AMD or DR is "Recognize people when they are nearby", and "Read text in normal size font in a newspaper or book", followed, in patients with AMD, by "Do things what you would like" and, in patients with DR, "Feeling frustrated by the vision problems." Regarding the treatment, the most relevant aspects for both groups is that the treatment works and receiving appropriate information before and after the treatment. The qualitative comments were focused to the disease, the treatment, and to the role of doctors and the health system. CONCLUSION: Quantitative responses and free comments can be useful to improve the care of patients with AMD or DR by physicians and the health system.

Influence of acid-etching after grit-blasted on osseointegration of titanium dental implants: in vitro and in vivo studies.

Rough implant surfaces have shown improved osseointegration rates. In a majority of dental implants, the microrough surfaces are obtained by grit blasting and/or acid-etching. The aim of this contribution was to evaluate the effects of acid-etching, after the grit-blasted treatment in titanium dental implants, on surface wettability, surface energy, osteoblast responses and its osseointegration behavior. Four surfaces were studied: as-machined, acid-etched, micro-rough by grit-blasting and the combination grit-blasted surface with acid-etched. The surfaces with increasing roughness show more osteoblastic adhered cells. This effect was most pronounced on samples blasted and blasted with acid-etching. The roughness obtained by grit-blasting is the main factor in comparison with the acid etching treatment in the biological response. These results were confirmed in vivo tests and histological analysis. The results demonstrated that the combination of the grit-blasted and acid-etched accelerated lightly bone regeneration at the different periods of implantation in comparison with the grit-blasted implants.

[Share experiment: hospital mobile pharmaceutical teams, a proven concept!]. / Partage d'expérience : les équipes pharmaceutiques mobiles à l'hôpital, un concept qui fait ses preuves !

A few months ago, the pharmacy department of the University Hospital of Poitiers was located in the basement of the hospital; communicating with care units by fax, phone or messenger. Today, drugs and medical devices, are stored in a 3400m(2) logistic platform and most of the delivery activity is robotized. Control and validation of prescriptions and dispensing activities are done by the pharmaceutical teams directly in the care units. Quality indicators allow us to improve our services regularly. A great success and interesting prospects for clinical pharmacy.

Role of glutathione S-transferases in melanoma susceptibility: association with GSTP1 rs1695 polymorphism.

BACKGROUND: Glutathione S-transferases (GSTs) GSTM1, GSTT1 and GSTP1 are multifunctional enzymes involved in the detoxification of a wide range of reactive oxygen species produced during melanin synthesis and oxidative stress processes. OBJECTIVES: Single nucleotide polymorphisms (SNPs) in GSTP1 and copy number variants in GSTM1 and GSTT1 may be candidate low-penetrance variants with a role in susceptibility to malignant melanoma (MM). METHODS: In this case-control study, 562 Spanish patients with sporadic MM and 338 cancer-free control subjects were included, and the role of polymorphisms in these GST genes was investigated. Genotypes were established by quantitative real-time polymerase chain reaction for GSTM1 and GSTT1 while TaqMan probes were used to genotype GSTP1 SNPs. RESULTS: The GSTP1 polymorphism rs1695, which encodes the amino acid change p.Ile105Val, was individually associated with MM [odds ratio (OR): 1·32, 95% confidence interval (CI): 1·06-1·63]. Furthermore, individuals carrying one or two MC1R nonsynonymous changes and GSTP1 rs1695 rare allele had an increased risk of developing MM (OR: 3·34, 95% CI: 1·42-8·09 and OR: 20·42, 95% CI: 2·80-417·42, respectively). CONCLUSIONS: This is the first time that the GSTP1 rs1695 polymorphism is reported to be associated with MM. In addition, this study is one of the largest GST polymorphism studies undertaken in the Spanish population and the first time that copy number variants have been scrutinized in relation to MM.

Cost-efficacy of adalimumab, etanercept, infliximab and ustekinumab for moderate-to-severe plaque psoriasis.

BACKGROUND: Different biological agents are used for the treatment of psoriasis. Previous data have shown adalimumab to be the most efficient drug in terms of cost-efficacy. However, newer data are required to include recent drugs. OBJECTIVE: To estimate the cost-efficacy ratios of biological agents licensed in Spain (adalimumab, etanercept, infliximab and ustekinumab) for the treatment of patients with moderate-to-severe psoriasis. METHODS: An economic evaluation model was developed by building a decision tree for each drug regimen for which scientific evidence was available. The payer perspective (Spanish National Health System) was considered, taking into account only the drug costs. Data on efficacy [proportion of patients with a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75)] reported in the randomized controlled trials were used. When more than one trial for each treatment had been published, a meta-analysis was performed. In case of weight-dependent doses (infliximab), weight of the study subjects was standardized by age and gender of the Spanish population, corrected for the increase in weight in subjects with psoriasis. Uncertainty was assessed by sensitivity analysis. RESULTS: Incremental efficacy ranged from 31.19% (etanercept at a dosage of 25 mg twice a week for 12 weeks) to 78.35% (infliximab at 5 mg/kg for 24 weeks). Efficiency, in terms of incremental cost-efficacy, ranged from 8013€ (adalimumab) to 17 981€ (ustekinumab at a dose of 90 mg) per PASI 75 responder gained. CONCLUSION: In terms of cost-efficacy, the most efficient biological drug was adalimumab. The robustness of this finding was confirmed by sensitivity analysis.

[Phenotypic and histologic characteristics of cutaneous melanoma in patients with melanocortin-1 receptor polymorphisms]. / Características fenotípicas e histológicas de los pacientes con melanoma cutáneo en función de los polimorfismos del MC1R.

BACKGROUND: The melanocortin-1 receptor (MC1R) is an important risk factor for melanoma due to its role in the production of melanin in response to sun exposure. OBJECTIVES: To analyze the phenotypic and histologic characteristics of cutaneous melanoma in patients carrying mutations in MC1R and assess the influence of sun exposure on the occurrence of melanoma. MATERIAL AND METHODS: A total of 224 patients with a diagnosis of melanoma seen in the Department of Dermatology at Hospital General Universitario Gregorio Marañón in Madrid, Spain between September 2004 and December 2009 were included in the study. The genomic sequence of MC1R was analyzed by polymerase chain reaction. RESULTS: At least one of the following MC1R variants was present in 58% of the patients: V60L, V92M, I155T, R160W, D294H, and R163Q. Carriers of those variants had a history of sunburn (P=.018) and melanomas located on areas with intermittent sun exposure (P=.019), and the majority had a diagnosis of superficial spreading melanoma. These associations were especially significant in patients with the R160W and D294H variants. Carriers of R160W also had melanomas associated with melanocytic nevi (P=.028). CONCLUSIONS: The results of our study suggest that there may be a relationship between the expression of certain MC1R variants and sun exposure, history of sunburn, and skin type. They also indicate a higher frequency of superficial spreading melanomas and melanomas associated with melanocytic nevi in patients carrying certain mutations in MC1R.

Phenotypic and histologic characteristics of cutaneous melanoma in patients with melanocortin-1 receptor polymorphisms.

BACKGROUND: The melanocortin-1 receptor (MC1R) is an important risk factor for melanoma due to its role in the production of melanin in response to sun exposure. OBJECTIVES: To analyze the phenotypic and histologic characteristics of cutaneous melanoma in patients carrying mutations in MC1R and assess the influence of sun exposure on the occurrence of melanoma. MATERIAL AND METHODS: A total of 224 patients with a diagnosis of melanoma seen in the Department of Dermatology at Hospital General Universitario Gregorio Marañón in Madrid, Spain between September 2004 and December 2009 were included in the study. The genomic sequence of MC1R was analyzed by polymerase chain reaction. RESULTS: At least one of the following MC1R variants was present in 58% of the patients: V60L, V92M, I155T, R160W, D294H, and R163Q. Carriers of those variants had a history of sunburn (P=.018) and melanomas located on areas with intermittent sun exposure (P=.019), and the majority had a diagnosis of superficial spreading melanoma. These associations were especially significant in patients with the R160W and D294H variants. Carriers of R160W also had melanomas associated with melanocytic nevi (P=.028). CONCLUSIONS: The results of our study suggest that there may be a relationship between the expression of certain MC1R variants and sun exposure, history of sunburn, and skin type. They also indicate a higher frequency of superficial spreading melanomas and melanomas associated with melanocytic nevi in patients carrying certain mutations in MC1R.

[Diagnostic utility of dermoscopy in pigmented actinic keratosis]. / Utilidad de la dermatoscopia en el diagnóstico de las queratosis actínicas pigmentadas.

The diagnosis of pigmented actinic keratosis can be complicated in clinical practice. The differential diagnosis with lentigo maligna melanoma can be difficult due to common clinical and dermoscopic characteristics. We present 5 cases of pigmented actinic keratosis in 4 patients. The most common dermoscopic finding was a grayish-brown granulation with a perifollicular distribution, present in all lesions, followed by rhomboidal structures in 4 cases, and an annular-granular pattern in 3. In no case were asymmetrical pigmented follicular openings observed. We draw attention to key findings that aid preoperative diagnosis of pigmented actinic keratosis.

Paediatric psoriasis--narrowband UVB treatment.

UNLABELLED: Narrowband UV-B is a safe and efficacious option for the treatment of adult psoriasis. However, the use of this therapy has been limited in children due to its long-term carcinogenic potential. It has proven to be an adequate alternative in patients whose condition is refractory to topical treatment. AIMS: To evaluate the efficacy and short-term safety of narrowband UV-B in the treatment of paediatric psoriasis, and to compare our results with those obtained in other studies on paediatric psoriasis. MATERIALS AND METHODS: Over a period of 2 years and 4 months, we administered narrowband UV-B to 20 children diagnosed with psoriasis that was refractory to topical therapy. The therapeutic response was measured using the Psoriasis Area and Severity Index (PASI). RESULTS: Between August 2005 and December 2007, 20 children received narrowband UV-B. Their median age was 13 years (range, 5-17 years), and the median initial PASI score was 8.25 (2.7-22.2). A median of 28 (10-59) sessions was required to achieve clearance, reaching almost complete or total remission (median final PASI) in all but two patients. Six patients required a new therapeutic course because of relapse, and the mean duration of remission was 8 months (4-18). No patients experienced severe adverse events during therapy, and only one discontinued treatment, for unrelated reasons. DISCUSSION AND CONCLUSION: Narrowband UV-B for the treatment of paediatric psoriasis has received little attention in the literature. This treatment has been limited in children because of its potential long-term carcinogenic effects, and most information has been extrapolated from adults. Nevertheless, narrowband UV-B phototherapy is an effective and well-tolerated therapeutic alternative in paediatric patients with severe psoriasis.

[Prevalence of eating disorders in early adolescent students]. / Prevalencia de trastornos alimentariosen estudiantes adolescentes tempranos.

OBJECTIVE: To measure the prevalence of Eating Behavior Disorders (EBD) in Spanish early-adolescent students using standardized methods. METHODS: A two-stage survey of prevalence of ED in a representative sample of 12 to 13 year old students in 2007 in Zaragoza (Spain). Standard evaluation: We used a two-phase cross sectional design, which involved the screening with questionnaires (EAT at a cutoff score of 20) and subsequent semi-structured interviews (SCAN) of screen-positive and screen-negative subjects. We calculated the sociodemographic characteristics, ED prevalence with their 95% confidence intervals (CI) with Confidence Interval Analysis (C.I.A.) disk version 2.0.0 (Altman et al, 2000). The study is financed by F.I.S. PI 05/2533 (Spain Health Department). RESULTS: In 2007 we studied 701 students seventh-grade, ages 12 to 13, girls and boys, in 9 public and private schools in Zaragoza (30 classrooms). In the second phase 164 preteens agreed to proceed with the clinical evaluation (63 at risk, high scorers; 101 selected sample not at risk). ED prevalence was 0.7% EDNOS F 50.9 (CI 95%: 0.3%-1.7%). CONCLUSION: The ICD-10 point prevalence rates of ED population in Spanish preteen students is similar to those reported for other developed countries. The prevalence of subclinical ED is substantially higher than that of full-syndrome.

[Clinical outcomes in patients with psoriasis following discontinuation of efalizumab due to suspension of marketing authorization]. / Evolución clínica de los pacientes psoriásicos tratados con efalizumab al suspender el fármaco.

INTRODUCTION: In February 2009, the European Medicines Agency suspended the marketing authorization for efalizumab after 3 confirmed cases of progressive multifocal leukoencephalopathy were reported. To assess the consequences of this decision, we performed a prospective follow-up study of patients in our department who were being treated with efalizumab at the time and compared clinical outcomes with data from the literature. PATIENTS AND METHODS: Thirty-two patients (28 with plaque psoriasis and 4 with palmoplantar psoriasis) were enrolled between February and March 2009. We recorded psoriasis area and severity index (PASI) scores at the moment of efalizumab discontinuation, at 6 weeks post-discontinuation, and at 3-monthly intervals thereafter. PASI scores prior to treatment with efalizumab were also noted. For patients who experienced rebounds with generalized psoriasis, we noted the time that had elapsed since efalizumab discontinuation and the treatment they were receiving. RESULTS: Even though 92.8% of the patients were considered good responders (>75% reduction in PASI score), 25% of the group (8/32) experienced rebound and 15.7% (5/32) experienced relapse. The percentage of patients in whom rebound was observed on transition therapy was 18% (2/11) for cyclosporin, 50% (1/2) for methotrexate, 50% (1/2) for adalimumab, 50% (1/2) for etanercept, and 27% (3/11) for topical treatment. CONCLUSIONS: We observed a very high rate of rebound and generalized inflammation in patients whose disease had previously been well controlled for several years.

Can ethanol affect the cell structure? A dynamic molecular and Raman spectroscopy study.

The role that tobacco consumption plays in the etiology of oral cancer carcinogenesis, and of alcohol consumption acting as a co-factor, have been well established. However, in recent years, the contribution of alcohol consumption alone to oral cancer has been proposed. In fact, a high percentage of patients who develop oral cancer have both habits (tobacco and alcohol consumption), and other small patient groups only consume alcohol or do not have any other identifiable bad habits. In the present study we demonstrate, using a combination of dynamic molecular modelling and Raman spectroscopy, that ethanol has a significant effect on oral cells in vitro, mainly interacting with the lipids of the cell membrane, changing their conformation. Thus, it is possible to conclude that ethanol can affect the cell permeability, and by consequence serve as a possible trigger in oral carcinogenesis.

SLC45A2: a novel malignant melanoma-associated gene.

Human pigmentation appears to be one of the strongest risk factors for malignant melanoma (MM). In humans, there is a long list of genes known to be involved in rare pigmentary disorders such as albinism. These genes explain most of the variation in pigmentation phenotypes seen in human populations, and they do this by regulating the level of synthesis, chemical composition, packaging, and distribution of melanin. This Spanish case-control study included 131 consecutive melanoma patients and 245 control subjects frequency-matched for sex and age. A total of 23 SNPs in six candidate genes (ASP, OCA2, TYR, TYRP1, SILV, and SLC45A) belonging to the pigmentation pathway were genotyped. We found that the variant allele of c.1122C>G, p.Phe374Leu (NCBI dbSNP rs16891982) in SLC45A2 (membrane associated transporter previously known as MATP) was associated with protection from MM (OR, 0.41; 95% CI, 0.24-0.70; P=0.008 after adjustment for multiple testing). This association was validated by the consistent link observed with dark hair, dark skin, dark eye color, and the presence of solar lentigins and childhood sunburns. This is the first time SLC45A2 has been described as a melanoma susceptibility gene in a light-skinned population.