Toenail zinc and risk of prostate cancer in the MCC-Spain case-control study.

BACKGROUND: Some researchers have suggested that zinc (Zn) could reduce the risk of prostate cancer (PC). However, research from observational studies on the relationship between PC risk and biomarkers of Zn exposure shows conflicting results. OBJECTIVES: To evaluate the association between toenail Zn and PC, considering tumour extension and aggressiveness, along with a gene-environment approach, exploring the interaction of individual genetic susceptibility to PC in the relationship between toenail Zn and PC. METHODS: In MCC-Spain study we invited all incident PC cases diagnosed in the study period (2008-2013) and recruited randomly selected general population controls. In this report we included 913 cases and 1198 controls with toenail Zn determined by inductively coupled plasma mass spectrometry. To measure individual genetic susceptibility, we constructed a polygenic risk score based on known PC-related single nucleotide polymorphisms. The association between toenail Zn and PC was explored with mixed logistic and multinomial regression models. RESULTS: Men with higher toenail Zn had higher risk of PC (OR quartile 4 vs.1: 1.41; 95% CI: 1.07-1.85). This association was slightly higher in high-grade PC [(ISUP≤2 Relative risk ratio (RRR) quartile 4 vs.1: 1.36; 1.01-1.83) vs. (ISUP3-5 RRR quartile 4 vs.1: 1.64; 1.06-2.54)] and in advanced tumours [(cT1-cT2a RRR quartile 4 vs.1: 1.40; 95% CI: 1.05-1.89) vs. (cT2b-cT4 RRR quartile 4 vs.1: 1.59; 1.00-2.53)]. Men with lower genetic susceptibility to PC were those at higher risk of PC associated with high toenail Zn (OR quartile 4 vs.1: 2.18; 95% CI: 1.08-4.40). DISCUSSION: High toenail Zn levels were related to a higher risk for PC, especially for more aggressive or advanced tumours. This effect was stronger among men with a lower genetic susceptibility to PC.

Toenail zinc as a biomarker: Relationship with sources of environmental exposure and with genetic variability in MCC-Spain study.

BACKGROUND: Toenails are commonly used as biomarkers of exposure to zinc (Zn), but there is scarce information about their relationship with sources of exposure to Zn. OBJECTIVES: To investigate the main determinants of toenail Zn, including selected sources of environmental exposure to Zn and individual genetic variability in Zn metabolism. METHODS: We determined toenail Zn by inductively coupled plasma mass spectrometry in 3,448 general population controls from the MultiCase-Control study MCC-Spain. We assessed dietary and supplement Zn intake using food frequency questionnaires, residential proximity to Zn-emitting industries and residential topsoil Zn levels through interpolation methods. We constructed a polygenic score of genetic variability based on 81 single nucleotide polymorphisms in genes involved in Zn metabolism. Geometric mean ratios of toenail Zn across categories of each determinant were estimated from multivariate linear regression models on log-transformed toenail Zn. RESULTS: Geometric mean toenail Zn was 104.1 µg/g in men and 100.3 µg/g in women. Geometric mean toenail Zn levels were 7 % lower (95 % confidence interval 1-13 %) in men older than 69 years and those in the upper tertile of fibre intake, and 9 % higher (3-16 %) in smoking men. Women residing within 3 km from Zn-emitting industries had 4 % higher geometric mean toenail Zn levels (0-9 %). Dietary Zn intake and polygenic score were unrelated to toenail Zn. Overall, the available determinants only explained 9.3 % of toenail Zn variability in men and 4.8 % in women. DISCUSSION: Sociodemographic factors, lifestyle, diet, and environmental exposure explained little of the individual variability of toenail Zn in the study population. The available genetic variants related to Zn metabolism were not associated with toenail Zn.

Toxic metals in toenails as biomarkers of exposure: A review.

Toenails have been used as biomarkers of exposure to toxic metals, but their validity for this purpose is not yet clear and might differ depending on the specific agent. To evaluate this issue, we reviewed the literature on: a) the time-window of exposure reflected by toenails; b) the reproducibility of toenail toxic-metal levels in repeated measures over time; c) their relationship with other biomarkers of exposure, and; d) their association with potential determinants (i.e. sociodemographic, anthropometric, or lifestyle characteristics) or with sources of exposure like diet or environmental pollution. Thus, we performed a systematic review, searching for articles that provided original data for levels of any of the following toxic metals in toenails: aluminum, beryllium, cadmium, chromium, mercury, nickel, lead, thallium and uranium. We identified 88 articles, reporting data from 67 different research projects, which were quite heterogeneous with regard to population profile, sample size and analytical technique. The most commonly studied metal was mercury. Concerning the time-window of exposure explored by toenails, some reports indicate that toenail cadmium, nickel and lead may reflect exposures that occurred 7-12 months before sampling. For repeated samples obtained 1-6 years apart, the range of intraindividual correlation coefficients of aluminum, chromium and mercury was 0.33-0.56. The correlation of toxic metal concentrations between toenails and other matrices was higher for hair and fingernails than for urine or blood. Mercury levels were consistently associated with fish intake, while other toxic metals were occasionally associated with specific sources (e.g. drinking water, place of residence, environmental pollution, and occupation). The most frequently evaluated health endpoints were cardiovascular diseases, cancer, and central nervous system diseases. Available data suggest that toenail mercury levels reflected long-term exposures and showed positive associations with fish intake. The lack of standardization in sample collection, quality control, analytical techniques and procedures - along with the heterogeneity and conflicting results among studies - mean it is still difficult to conclude that toenails are a good biomarker of exposure to toxic metals. Further studies are needed to draw solid conclusions about the suitability of toenails as biomarkers of exposure to toxic metals.

Toenails as a biomarker of exposure to arsenic: A review.

This systematic review summarizes the current evidence related to the reliability of toenail total arsenic concentrations (thereafter "arsenic") as a biomarker of long-term exposure. Specifically, we reviewed literature on consistency of repeated measures over time, association with other biomarkers and metal concentrations, factors influencing concentrations, and associations with health effects. We identified 129 papers containing quantitative original data on arsenic in toenail samples covering populations from 29 different countries. We observed geographic differences in toenail arsenic concentrations, with highest median or mean concentrations in Asian countries. Arsenic-contaminated drinking water, occupational exposure or living in specific industrial areas were associated with an increased toenail arsenic content. The effects of other potential determinants and sources of arsenic exposure including diet, gender and age on the concentrations in toenails need further investigations. Toenail arsenic was correlated with the concentrations in hair and fingernails, and with urine arsenic mainly among highly exposed populations with a toenail mean or median ≥1 µg/g. Overall, there is a growing body of evidence suggesting that arsenic content from a single toenail sample may reflect long-term internal dose-exposure. Toenail arsenic can serve as a reliable measure of toxic inorganic arsenic exposure in chronic disease research, particularly promising for cancer and cardiovascular conditions.

Dietary Zinc and Risk of Prostate Cancer in Spain: MCC-Spain Study.

Zinc is a key trace element in normal prostate cell metabolism, and is decreased in neoplastic cells. However, the association between dietary zinc and prostate cancer (PC) in epidemiologic studies is a conflicting one. Our aim was to explore this association in an MCC-Spain case-control study, considering tumor aggressiveness and extension, as well as genetic susceptibility to PC. 733 incident cases and 1228 population-based controls were included for this study. Dietary zinc was assessed using a food frequency questionnaire, and genetic susceptibility was assessed with a single nucleotide polymorphisms (SNP)-based polygenic risk score (PRS). The association between zinc intake and PC was evaluated with mixed logistic and multinomial regression models. They showed an increased risk of PC in those with higher intake of zinc (Odds Ratio (OR) tertile 3vs1: 1.39; 95% Confidence interval (CI):1.00⁻1.95). This association was mainly observed in low grade PC (Gleason = 6 RRR tertile 3vs1: 1.76; 95% CI:1.18⁻2.63) as well as in localized tumors (cT1-cT2a RRR tertile 3vs1: 1.40; 95% CI:1.00⁻1.95) and among those with higher PRS (OR tertile 3vs1: 1.50; 95% CI:0.89⁻2.53). In conclusion, a higher dietary zinc intake could increase the risk of low grade and localized tumors. Men with higher genetic susceptibility0020might also have a higher risk of PC associated with this nutrient intake.

Elastolytic Actinic Giant Cell Granuloma.

Actinic granuloma and annular elastolytic giant cell granuloma are different terms used to define skin lesions characterized by elastolysis, elastophagocytosis, and multinucleated giant cell infiltrate. The clinical appearance varies from papules to annular plaques. Although elastolytic actinic giant cell granuloma shares some clinical features with granuloma annulare, they can be differentiated by histopathologic findings. The disease is initiated by an immune response triggered by different factors that alter the elastic tissue. The course tends to be chronic, with variable response to treatments, although spontaneous remission may occur. Diabetes mellitus is the systemic disease most frequently associated with this condition.

Photoletter to the editor: Basal cell carcinoma on the vermilion lip.

The vermilion and vermilion border are rare locations for basal cell carcinoma. We report a case of a 72-year-old woman, who presented with an asymptomatic erosive lesion on the vermilion area of the upper lip. Histopathology examination was consistent with basal cell carcinoma. We suggest that basal cell carcinoma should be included in the differential diagnosis of erosive/ulcerative lesions arising on the vermilion area of the lip.

Annular elastolytic giant cell granuloma associated to late-onset X-linked dominant protoporphyria.

X-linked dominant protoporphyria (XLDPP) is a genetic disorder that affects the synthesis of the heme group due to an increase in delta-aminolaevulinate synthase 2 (ALAS2) enzyme activity. Moreover, annular elastolytic giant-cell granuloma (AEGCG) is a rare reactive granulomatous dermatosis, usually associated with actinic damage. An 86-year-old man presented with edematous-erythematous lesions in photoexposed areas of the face and on the dorsum of both hands. Protoporphyrin levels in serum and feces were significantly elevated and a heterozygous frameshift mutation in the exon 11 of the ALAS2 gene: c.1706-1709del (p.Glu569GlyfsX24) was identified. Concomitantly, we observed an annular plaque with raised borders on the back of his right hand, clinically and histologically compatible with a diagnosis of AEGCG. Skin lesions disappeared only upon use of a physical sunscreen. We report two rare photodermatoses in an elderly patient and discuss the significance of dermal elastic fiber damage induced by the XLDPP as a main triggering factor of AEGCG.

Elastolytic giant cell granuloma: clinic-pathologic review of twenty cases.

BACKGROUND: O'Brien described four histopathological patterns of actinic granuloma (AG). Since then, only single cases and a few series have been reported in the literature, most corresponding to cases of the giant cell type. METHODS: We reviewed all the cases diagnosed as AG or elastolytic giant cell granuloma (EGCG) in our department from 1988 until 2010. The biopsies were classified into the four patterns previously described. RESULTS: Giant cell pattern was found to be the most frequent (70% of the cases). In four cases, the biopsies showed more than one histopathologic pattern. All the lesions were located on sun-exposed areas or were related to chronic heat exposure. Diabetes mellitus was associated in 40 % of the cases. CONCLUSIONS: The giant cell pattern of EGCG is the most frequent. Some cases may share histopathologic features of more than one variant and thus, we consider they may be categorized as mixed patterns. Diabetes mellitus is the most common associated disease and should always be ruled out.

Granuloma annulare photoinduced by paroxetine.

Granuloma annulare (GA) is a benign granulomatous skin disease with several clinical manifestations and characteristic histological findings. GA located in photoexposed areas is a rare finding and its association to a drug-induced systemic photosensitivity is even less common. To the best of our knowledge, only one case of systemic drug photosensitivity manifesting as a GA has been reported. We describe a patient with systemic photosensitivity to paroxetine with clinical and histological manifestations of GA, which was confirmed by the photobiological study. The phototest revealed a reduction of the minimal erythematous dose for UVB while taking the paroxetine and its normalization after its withdrawal, which was accompanied by the clinical resolution of the skin eruption. The manifestation of systemic drug photosensitivity as a GA like in our case is exceptional.

Letter: Cutaneous mastocytosis with systemic involvement mimicking clinical and dermatoscopically multiple melanocytic nevi.

Mastocytosis can sometimes resemble other skin conditions, especially pigmented ones, not only clinically but also dermatoscopically. We report the case of a woman with the diagnosis of cutaneous mastocytosis mimicking multiple melanocytic nevi. Melanocytic stimulation can be induced by high levels of stem cell factor. The progressive increase in the number of pigmented lesions in a patient should lead us to perform a biopsy to search for mastocytosis.