The relationship between the epidermal growth factor (EGF) 5'UTR variant A61G and melanoma/nevus susceptibility

The inheritance of a G allele in position 61 in the 5'UTR of the epidermal growth factor (EGF) gene has been reported to increase melanoma susceptibility, a finding we have investigated in this study. The most potent phenotypic risk factor for melanoma is the atypical mole syndrome (AMS) phenotype. Our hypothesis is that the AMS is genetically determined and that nevus genes are also low penetrance melanoma susceptibility genes. We report that the G allele frequencies were the same in 697 healthy women and 380 melanoma cases (OR 0.97, 95% CI 0.8-1.2 p=0.76). We therefore found no evidence that this polymorphism is a melanoma susceptibility gene. Furthermore, we found no evidence that the polymorphism controls the nevus phenotype (nevus number, number atypical nevi or AMS phenotype). We did find some evidence that the G allele may be associated with decreased tumor Breslow thickness (OR 0.5, 95% CI 0.3-0.9) for the A/A genotype versus A/G and G/G combined in tumors of thickness >3.5 vs < or =3.5 mm and may therefore act as a predictor of survival, although this finding is not in accord with the original report. This is the second study to find no association between EGF +61 and melanoma susceptibility.     

Association between cutaneous melanoma, Breslow thickness and vitamin D receptor BsmI polymorphism

BACKGROUND: Literature data report an association between some vitamin D receptor (VDR) polymorphisms and different kinds of tumours, including malignant melanoma (MM). Only three VDR polymorphisms (FokI, TaqI and A-1012G) have been investigated in association with the presence of cutaneous MM or the development of metastases. OBJECTIVES: The present paper analyses for the first time the association between BsmI polymorphism and MM prevalence together with Breslow thickness. In addition, the FokI single nucleotide polymorphism was also determined. METHODS: One hundred and one patients with MM and 101 healthy donors matched for age and sex were enrolled. Molecular VDR typing was performed by means of restriction fragment length polymorphism analysis. RESULTS: All cases and controls were in Hardy-Weinberg equilibrium for BsmI, FokI and A-1012G. Significant associations were found between the BsmI bb genotype frequency and MM (P = 0.02) along with Breslow thickness (P = 0.001). This same behaviour was not observed for the FokI or A-1012G polymorphisms. Multivariate logistic regression analysis confirmed these significant results after correction for age, gender, skin type and MM localization. CONCLUSIONS: Although the biological meaning of the effects exerted by BsmI polymorphism is still under debate, the statistical association found in the present study suggests that further work should be done to verify this variant as a possible risk marker for MM and its aggressiveness, also considering that the real association may be due to other unknown genes linked to the BsmI b allele.     

Metallothionein-overexpression as a prognostic factor for progression and survival in melanoma. A prospective study on 520 patients

BACKGROUND: Metallothioneins (MTs) are ubiquitous proteins with high affinity for heavy metal ions, e.g. zinc, copper and cadmium. In the last decade it has been shown that MT overexpression in a variety of cancers is associated with resistance to anticancer drugs and radiotherapy, and with a poor prognosis. OBJECTIVES: To examine the role of MT overexpression in melanoma patients as a prognostic factor for progression and survival. METHODS: In a prospective cohort study 760 patients with primary cutaneous melanoma were investigated over 5 years (1993-98) by using a monoclonal antibody (E9) against MT on routinely fixed and paraffin-embedded tissues. In total, 520 patients were able to be followed up for progression of their disease or death due to melanoma and were included for statistical analysis (Fisher's exact test, Mantel-Haenszel chi2 test, Kaplan-Meier curves). MT data, progress-free interval and overall survival were compared univariately and multivariately with other prognostic factors, e.g. Breslow thickness, Clark level, ulceration, localization, age and gender (Cox regression analysis). RESULTS: The immunohistochemical overexpression of MT in tumour cells (cut-off level > 10% of all tumour cells) in patients with primary melanoma (156 of 520; 30%) was associated with a higher risk for progression of the disease (33 of 45; 73%) and reduced survival (24 of 30; 80%) than MT-negative lesions [364 of 520 (70%), 12 of 45 (27%) and six of 30 (20%), respectively (P < 0.0001)]. Similarly, Kaplan-Meier tumour-free survival and overall survival curves for the comparison of MT-positive and MT-negative tumours gave highly significant advantages for the MT-negative group. In a univariate analysis (comparison with Breslow thickness: relative risk 2.9, 95% confidence interval, CI 1.46-5.76, P = 0.0023 for progression; relative risk 4.19, 95% CI 1.73-10.19, P = 0.0015 for survival), as well as in a multivariate analysis with other prognostic markers, MT overexpression turned out to be a highly significant and independent factor for prognosis in primary melanoma. CONCLUSIONS: MT overexpression in primary melanoma is associated with an increased risk for disease progression. This marker is independent from Breslow thickness and helps to identify those thin melanomas (< 1.5 mm) that are at increased risk of progression. Moreover, the immunohistochemical staining of paraffin material is a cheap, easy and widely available technique to gain these results.     

系统性红斑狼疮患者白介素10受体cDNA基因多态性研究

目的 探讨白介素10受体(IL-10R)的两个基因位点G241A和G520A基因多态性与系统性红斑狼疮(SLE)患者发病的相关性.方法 采用聚合酶链反应-单链构象多态性(PCR-SSCP)和聚合酶链反应限制性片段多态性(PCR-RFLP)及DNA测序方法进行基因分型.结果 IL-10R2基因型与SLE易感性显著相关.G520/G520基因型增加SLE发病危险性,P=0.004,OR=0.515,95%的可信区间为0.444-0.579;G520/A520基因型增加SLE发病危险性,P=0.055,OR=1.968,95%的可信区间为0.981-3.949.IL-10R1基因型与SLE易感性无显著相关.各个基因型组合的分布情况和优势比显示具有IL-10R1 G241/G241基因型和IL-10R2 G520/G520的个体SLE发病危险性明显高于其他的基因型组合,P=0.004,OR=0.515,95%的可信区间为0.444-0.597.结论 IL-10R2基因型与SLE易感性显著相关,G520/G520基因型增加SLE发病危险性.具有IL-10R1 G241/G241基因型和IL-10R2 G520/G520的个体SLE发病危险性明显高于其他的基因型组合.     

外伤相关黑素瘤87例临床病理特点与预后分析

目的:分析外伤相关黑素瘤的临床病理特点及其与患者预后间的关系。方法:回顾性分析2009—2020年第四军医大学西京皮肤医院87例外伤相关黑素瘤的临床病理特点,通过Mann-Whitney检验分析不同年龄、性别患者间肿瘤Breslow厚度的差异;通过Spearman秩相关分析外伤至发现皮疹的时间与Breslow厚度之间的...     

Mitotic rate and subcutaneous involvement are prognostic factors for survival after recurrence in patients with only locoregional skin metastasis as the first site of recurrence from cutaneous melanoma

Background Few reports on literature give detailed figures on prognostic factors of locoregional skin recurrence in cutaneous melanoma. Objective The aim of this study was to evaluate clinical and histological prognostic factors following development of locoregional cutaneous metastasis as the only progression site from melanoma. Methods Data from 1327 stage I and II melanoma patients who visited Instituto Valenciano de Oncología and Consorcio Hospital General Universitario de Valencia from 2000 to 2010 were documented in a prospective manner. During follow up, 112 (8.4%) of them developed recurrent disease. A retrospective analysis revealed a subset of 36 patients with locoregional cutaneous metastases as a first event. Results Significant prognostic factors in the univariate analysis were Breslow thickness, tumor mitotic rate and the presence subcutaneous involvement of the skin metastasis. After multivariate analysis the independent predictive factors for survival after recurrence were tumor mitotic rate (hazard ratio [HR]: 8.6; 95% CI: 1.0–77.2) and subcutaneous involvement of the skin metastasis (HR: 4.3; 95% CI: 1.0–18.5). Conclusion The survival after recurrence of melanoma patients that has relapsed with only locoregional cutaneous metastasis depends on the mitotic rate of the primary tumor and the subcutaneous involvement of the metastasis.     

Hazard-rate analysis in state I malignant melanoma

Hazard-rate analysis provides a unique means of assessing prognosis in patients with malignant disease. The hazard rate is the probability of a patient dying within a particular unit of time after definitive therapy. Hazard-rate analysis was performed on a series of 719 consecutive patients with clinical stage I cutaneous malignant melanoma (MM). The peak hazard rate for death from metastatic MM occurred during the 48th month of follow-up. Thereafter, the hazard rate declined and approached zero by the 120th month. When the patients were stratified by the thickness of their primary MM, thicker lesions reached their peak hazard-rate month earlier than thinner lesions. We conclude that after 120-month survival, the risk of dying from MM is virtually zero. However, since rare late deaths from MM occur, lifetime follow-up is recommended.     

Gene polymorphisms (G82S, 1704G/T, 2184A/G and 2245G/A) of the receptor of advanced glycation end products (RAGE) in plaque psoriasis

Having in mind the relationships among oxidative stress, psoriasis and common disorders, the association between polymorphisms in the gene encoding the receptor for advanced glycation end products (RAGE) and plaque psoriasis, including patients with a personal history of diabetes mellitus, cardiovascular disorders, cancer and allergy, was investigated. The allele frequencies and genotype distribution combinations of the four polymorphisms in the RAGE gene (6p21.3, G82S, 1704G/T, 2184A/G and 2245A/G) were compared in a case-control study of 272 subjects (130 patients with plaque psoriasis and 142 healthy control subjects of comparable age and sex distribution). The polymerase chain reaction with subsequent restriction analysis was used for detection of genotype variants. There was a significantly higher frequency of the 2184G allele of the 2184A/G RAGE polymorphism in psoriatic patients than in the control subjects (odds ratio 2.18, 95% CI 1.32-3.59, P=0.001). The 2184G allele occurred more often in psoriatic patients with a negative history of cardiovascular diseases (odds ratio 2.38, 95% CI 1.35-4.18, P=0.001, Pcorr=0.004), in those with a negative history of diabetes mellitus (odds ratio 2.05, 95% CI 0.1.22-3.45, P=0.004, Pcorr=0.012) and in those with a negative history of cancer (odds ratio 1.97, 95% CI 1.17-3.31, P=0.007, Pcorr=0.014) compared with the corresponding control subjects. We conclude that the 2184G allele of the RAGE gene is a significant risk factor for plaque psoriasis. The risk is associated with the non-presence of some common, especially cardiovascular, diseases in psoriatic patients.     

Tumor necrosis factor alpha promoter-308G/A polymorphism in Mexican patients with patchy alopecia areata

Background Alopecia areata (AA) is a chronic inflammatory condition characterized by hair loss, most frequently from the scalp. Its etiopathogenesis is currently unknown, but inflammatory traits and associations with autoimmune diseases suggest that AA shares a similar origin. The tumor necrosis factor alpha (TNFα) gene, located on chromosome 6 within the major histocompatibility complex class III gene, may carry previously described polymorphisms – particularly in the promoter region, such as TNFα‐308G/A – known to be risk factors in a wide variety of inflammatory pathologies. In Mexican populations, this polymorphism has been associated with augmented TNFα production and, thus, renders carriers more susceptible to developing autoimmune diseases; however, as yet it has not been associated with AA. Objectives To assess a possible association between the presence of TNFα‐308G/A and patchy AA. Materials and methods Blood samples were taken from 59 patients affected by patchy AA and 103 control subjects without AA, all from the northeastern Mexican population. Genomic DNA was isolated using the phenol‐chloroform method and samples subjected to polymerase chain reaction‐restriction fragment length polymorphism in order to detect the TNFα‐308G/A polymorphism. Results TNFα‐308G/A (TNF2) allele [odds ratio (OR) = 3.22, P = 0.026, 95% confidence interval (CI) = 0.99–11.61], when segregated in the heterozygous (TNF1/TNF2) genotype (OR = 3.53, P = 0.023, 95% CI = 1.01–12.89) confers a significant risk for developing AA, compared with the genotype TNF1/TNF1 observed in controls (OR = 0.28, P = 0.023, 95% CI = 0.08–0.99). Conclusions Our data suggest that there is a plausible association between the presence of the TNFα‐308G/A polymorphism and a higher susceptibility for developing patchy AA. This risk might be due to overproduction of TNFα, which would facilitate an autoimmune response against the hair follicle.     

Improved survival for melanoma in Northern Ireland: a comparison of two 5-year periods (1984-88 and 1994-98)

BACKGROUND: The incidence of cutaneous malignant melanoma has been rising steadily in Caucasian populations for several decades, with a doubling time of 10-14 years. An increase in incidence of about 5% per year has been reported in most Caucasian populations since the early 1960s. OBJECTIVES: This study was designed to determine the changing incidence of primary cutaneous malignant melanoma in Northern Ireland and to examine changes in survival rates from cutaneous malignant melanoma in two 5-year periods, 1984-88 and 1994-98. METHODS: One thousand three hundred and twenty-six patients with invasive primary cutaneous melanoma were included in the study. RESULTS: The age standardized rate of melanoma rose from 4.3 per 100,000 population per year in men and 8.6 per 100,000 population per year in women to 7.7 and 11.8, respectively, per 100,000 population per year in the 1994-98 period. Overall, the absolute 5-year survival for the 1984-88 period was 71.0% [95% confidence interval (CI) 66.9-75.1%] and 77.4% (95% CI 73.4-81.4%) for the 1994-98 period. Women consistently showed better survival at all ages and within almost all categories of thickness of primary tumour. Younger patients of both sexes showed better survival rates. CONCLUSIONS: When survival rates between the 1984-88 and 1994-98 periods were compared using multivariate analysis, we found that patients diagnosed in the second period had a one-third lower risk of dying than those in the earlier period. Much of this reduction was explained by changes in the number of melanomas of thin Breslow depth and ulcerated melanomas.     

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.     

Clinical correlates of Breslow thickness of malignant melanoma

BACKGROUND: Breslow thickness is a major predictor of prognosis in cutaneous malignant melanoma (MM) and patients continue to present with thick lesions, which have a poorer prognosis. OBJECTIVES: To investigate correlations of Breslow thickness with demographic variables, tumour site, clinical features, false negative diagnostic rate and clinic of primary referral. METHODS: Data were obtained from the records of 738 patients with histologically diagnosed cutaneous MM. Tumours included were in situ and invasive MM and lentigo maligna melanoma. In view of the skewed distribution of MM thickness, categories of MM thickness were used for analysis, using the commonly applied cut-offs of 0.75, 1.5 and 3.5 mm. The variables investigated were particularly associated with changes in the proportion of the thickest group, 'thick' MMs. The proportion of this thickness category is proposed as an appropriate and sensitive variable for the investigation of correlations with MM thickness. Thickness >/= 1.5 mm has also been considered in view of its prognostic significance. RESULTS: Results were similar for the two thickness groups, but more significant for the thick group. The previously described correlations of tumour thickness and increasing age (P < 0.00001) and location on head and neck (P = 0.0002), together with the independence of these variables, have been confirmed. The correlation with male gender was also confirmed but this was weak (P = 0.05). Novel findings were correlations of Breslow thickness with all features of the seven-point checklist (P varying from P = 0.01 to P < 0.00001) and tumour elevation (P < 0.00001). In general in the seven-point checklist, the absence of the major features (except variation in size) (P < 0.00001) and presence of minor features (except altered sensation) (P varying from P = 0.004 to P < 0.00001) were strongly associated with thick MMs. These results for tumour thickness are a further argument for retention of the minor features of the seven-point checklist. False negative diagnosis was found to be correlated with tumour thickness (P < 0.02) but this relationship was lost on multivariate analysis with inclusion of the clinical features. MM thickness was highly correlated with primary referral clinic (P < 0.00001). Only approximately 8% of MMs presenting to the Pigmented Lesion Clinic (PLC) were thick, while the proportion presenting to general dermatology was about three times greater and to plastic surgery about five times greater. This was maintained on multivariate analysis, including all other variables and, therefore, there must be other determining factors of referral not examined in the study. Conclusion MM thickness is associated with increasing age, male gender, location on the head and neck, all features of the seven-point checklist, tumour elevation and referral to the PLC. It is important to investigate further the reasons for general practitioner referral of different thickness MM to different types of clinic, as referral to clinics other than the PLC results in delay in the first hospital appointment, and it is now apparent that thicker lesions are disproportionately affected.     

Downregulation of cell cycle modulators p21, p27, p53, Rb and proapoptotic Bcl-2-related proteins Bax and Bak in cutaneous melanoma is associated with worse patient prognosis: preliminary findings

BACKGROUND: Cutaneous melanoma is a tumor with high metastatic potential, but the mechanisms leading to progression are still not fully understood. To provide further molecular basis for understanding the progression of melanoma, the aim of this study was to examine the expression pattern of cell cycle modulators (p21, p27, p53 and Rb) and proapoptotic multidomain Bcl-2 related proteins (Bax and Bak) and to analyze its differences in patients with and without progression stages. METHODS: We have studied 31 patients with cutaneous melanoma at stage IIa (Breslow thickness 1.5-4.0 mm), and follow them for 10-year period. Eighteen of these patients developed metastasis. The determination of selected molecular markers participating in cell cycle regulation and apoptosis was performed by immunohistochemistry. RESULTS: We have observed a significant increase in the loss of expression of the Bax, Bak, p21, p27, p53 and Rb. The analysis of the relationship between these downregulated markers and Breslow thickness showed significant positive correlation (r=0.556, p=0.029) and predictive value if thickness below 2.3 mm (OR=3.0, 95% CI=0.312-28.84). CONCLUSIONS: Our study showed that the downregulation of the markers associated with cell cycle control and apoptosis is of great value in predicting malignant transformation and in assessing the risk of metastases development for 10-year follow-up period.     

Efficacy of positron emission tomography and computed tomography in clinical staging of cutaneous malignant melanoma

Accurate staging is very important for determining the prognosis and appropriate treatment for malignant melanoma (MM). The aim of this study is to determine the effectiveness of positron emission tomography and computed tomography (PET/CT) imaging in staging MM. Patients diagnosed with MM who then underwent PET/CT metastasis before treatment were assessed retrospectively. For each patient, the following variables were recorded: Breslow thickness, Clark's level, number of mitoses, the presence of ulceration detected in the pathology report, and the presence of lymph nodes and/or distant metastases detected by PET/CT. The pathology and PET/CT reports of 139 patients (79 female and 60 male) were retrospectively evaluated for staging after MM diagnosis. Patients with a Breslow thickness greater than 3.4 mm and Clark's level of 4 to 5 were found to be statistically significantly higher with regional lymph node metastasis after PET/CT scans. Patients with Breslow thickness greater than 2.85 mm and Clark's level of 4 to 5 were found to be statistically significantly higher with distant metastasis after PET/CT scan. The results of our study suggest that PET/CT imaging for metastasis scanning, starting with T2 patients, may be used in MM staging to reduce the need for sentinel lymph node (SLN) biopsy and lymph node dissection.     

A functional single-nucleotide polymorphism in the catechol-<Emphasis Type="Italic">O</Emphasis>-methyltransferase gene alter vitiligo risk in a Chinese population

Vitiligo is an acquired hypomelanotic skin disorder resulting from the loss of functional melanocytes. The COMT-158 polymorphism can reduce COMT enzyme activity and may thus lead to the overproduction of toxic radicals in the melanocyte microenvironment. To determine whether this polymorphism in the COMT gene is associated with an increased risk of vitiligo in Chinese populations, we used a polymerase chain reaction sequence-specific primer (PCR-SSP) technique to determine the frequency of the polymorphism COMT-158 G > A in 749 vitiligo patients and 763 healthy controls. We found that compared to the COMT-158 GG genotype, the COMT-158 GA genotype (adjusted odds ratio [OR], 1.39; 95% confidence interval [CI], 1.13–1.72) and the combined GA + AA genotype (adjusted OR, 1.41; 95% CI, 1.15–1.74) were associated with an increased risk of generalized vitiligo. The association was more pronounced in patients with early-onset vitiligo (adjusted OR, 1.95; 95% CI, 1.45–2.60), those with a family history of vitiligo (adjusted OR, 3.84; 95% CI, 2.47–5.96), and female patients (adjusted OR, 1.74; 95% CI, 1.29–2.36). When we further clinically stratified the vitiligo patients according to their disease types, we found that the combined GA + AA genotype was associated with vitiligo vulgaris (adjusted OR, 1.31; 95% CI, 1.02–1.68), focal vitiligo (adjusted OR, 1.62; 95% CI, 1.17–2.25), and universal vitiligo (adjusted OR, 1.50; 95% CI, 0.98–2.30), but not with acrofacial vitiligo (adjusted OR, 1.53; 95% CI, 0.86–2.73) or segmental vitiligo (adjusted OR, 1.35; 95% CI, 0.72–2.51). In conclusion, this COMT gene polymorphism may have contributed to the etiology of vitiligo in our Chinese population. Larger population-based studies are required to verify our findings.     

In vivo reflectance confocal microscopy enhances secondary evaluation of melanocytic lesions

We recently described an in vivo reflectance confocal microscopy (RCM) method and our aim was to evaluate a possible additive value of this type of analysis in the management of melanocytic lesions. In two referral centers (Sydney and Modena), lesions (203 nevi and 123 melanomas (MMs) with a median Breslow thickness of 0.54 mm) were excised on the basis of clinical suspicion (history, dermoscopy examination, and/or digital monitoring). The RCM method was also trialed on a non-biopsied population of 100 lesions, which were clinically and dermoscopically diagnosed as benign nevi. All RCM and dermoscopy diagnoses were performed blinded to the histopathological diagnosis. Firstly, in the study population, a high interobserver agreement (on a subset of 90 lesions) was seen with the RCM method, which had superior specificity (68%, 95% confidence interval (95% CI): 61.1-74.3) for the diagnosis of MM compared with dermoscopy (32%, 95% CI: 25.9-38.7), while showing no difference in sensitivity (91%, 95% CI: 84.6-95.5, RCM; 88%, 95% CI: 80.7-92.6 dermoscopy). The two techniques had a weak correlation, resulting in only 2.4% of MMs being misclassified by both techniques. Diagnosis of light-colored lesions is improved by RCM (specificity 84%, 95% CI: 66.3-94.5) compared with dermoscopy (specificity 39%, 95% CI: 23.7-56.2). Secondly, the RCM method classified 100% of the non-biopsied control nevi population as benign.     

p53 codon 72 Pro homozygosity increases the risk of cutaneous melanoma in individuals with dark skin complexion and among noncarriers of melanocortin 1 receptor red hair variants

BACKGROUND: p53 has a common polymorphism at amino acid 72, encoding either arginine or proline. p53Arg and p53Pro exhibit differences in various biological activities, such as cell-cycle arrest and induction of apoptosis. Numerous epidemiological studies have examined the role of this polymorphism in several human malignancies, including cutaneous cancers, with contradictory results. OBJECTIVES: To investigate the germline frequency of p53 codon 72 polymorphism in malignant melanoma in a Mediterranean population, and to examine possible associations with various clinicopathological factors. METHODS: In this hospital-based case-control study we used allele-specific polymerase chain reaction for p53 codon 72 genotyping in blood specimens from 107 Greek patients with sporadic cutaneous melanoma and 145 healthy controls. RESULTS: After adjustment for age, sex and phototype the Pro/Pro genotype was associated with increased risk for cutaneous melanoma compared with the Arg/Arg genotype (adjusted odds ratio, OR 3.17, 95% confidence interval, CI 1.03-9.78). This correlation was more pronounced in subjects with phototypes III or IV (adjusted OR 9.56, 95% CI 1.56-58.46), dark skin (adjusted OR 10.96, 95% CI 1.64-73.28), dark eyes (adjusted OR 8.86, 95% CI 1.69-46.52) and dark hair (adjusted OR 3.17, 95% CI 1.01-9.95), and among noncarriers of melanocortin 1 receptor gene (MC1R) red hair polymorphisms (adjusted OR 2.99, 95% CI 1.02-8.78). CONCLUSIONS: p53 codon 72 Pro/Pro genotype could be a risk factor for the development of melanoma in the Greek population, especially in subgroups with darker skin pigmentation, as well as among noncarriers of the MC1R red hair polymorphic variants.