A b s t r a c tThe complex structure of human skin and its physicochemical properties turn it into an efficient outermost defence line against exogenous factors, and help maintain homeostasis of the human body. This role is played by the epidermal barrier with its major part -stratum corneum. The condition of the epidermal barrier depends on individual and environmental factors. The most important biophysical parameters characterizing the status of this barrier are the skin pH, epidermal hydration, transepidermal water loss and sebum excretion. The knowledge of biophysical skin processes may be useful for the implementation of prophylactic actions whose aim is to restore the barrier function.Key words: epidermal barrier, sebum, skin hydration, transepidermal water loss, skin pH. Skin is a barrier between the human body and the external environment. It protects the body against exogenous chemical and physical factors, takes part in the metabolic processes, plays a resorptive and thermoregulatory function, being the first line of defence against pathogenic microorganisms, and it partakes in immunological processes [1]. Review paperThe complex structure of human skin and its physicochemical characteristics turn it into an effective outermost defence line against exogenous factors, and help maintain homeostasis of the human body. This role is played by the epidermal barrier, in which the corneal layer of epidermis has a particularly important function to perform [1][2][3]. It consists of 15-20 layers of fully cornified keratinocytescorneocytes. In the bottom part of the cornified layer, the cells closely adjoin each other, while in the top part they are arranged loosely and undergo scaling. Construction of the corneal layer resembles a wall in which corneocytes stand for bricks, and a fat-abundant intercellular matrix is the cement [4,5]. The interior of the corneal layer cells is filled with cytokeratin filaments bonded with filaggrin. These cells are surrounded by a stiff, cornified encasement built mostly of the loricrin protein, forming a part of the so-called protein-lipid envelope [2,3,6]. The envelope is connected with the extracellular liquid crystal matrix and constitutes the border between the hydrophilic surface of the cells and the lipophilic non-polar fatty acids of the matrix surrounding corneocytes [7].The thickness of the outer layer of the epidermis, the size of corneocytes, and the composition of superficial lipids impact the regenerative properties of the skin, which contributes to the various courses of dermatological diseases, and the process of healing alike. Anatomical areas with thick epidermis are more resistant to external factors [8]. On the other hand, the areas with a relatively thin cornified layer, such as the face, are characterized by high susceptibility to damaging factors, but also by the ability to re-establish the barrier function very fast. It is connected with a high proliferative activity, thus quick regeneration of the epidermis, intensive vascularity, good hydration, and pr...
Xeroderma pigmentosum is a rare autosomal recessive disease that is associated with a severe deficiency in nucleotide excision repair. The presence of a distinct the nucleotide excision repair (NER) mutation signature in melanoma suggests that perturbations in this critical repair process are likely to be involved with disease risk. We hypothesized that persons with polymorphic NER gene(s) are likely to have reduced NER activity and are consequently at an increased risk of melanoma development. We assessed the association between 94 SNPs within seven XP genes (XPA-XPG) and the melanoma risk in the Polish population. We genotyped 714 unselected melanoma patients and 1,841 healthy adults to determine if there were any polymorphisms differentially represented in the disease group. We found that a significantly decreased risk of melanoma was associated with the Xeroderma pigmentosum complementation (XPC) rs2228000_CT genotype (odds ratio [OR] 5 0.15; p < 0.001) and the rs2228000_TT genotype (OR 5 0.11; p < 0.001) compared to the reference genotype. Haplotype analysis within XPC revealed the rs2228001_A 1 G1475A_G 1 G2061A_A 1 rs2228000_T 1 rs3731062_C haplotype (OR 5 0.26; p < 0.05) was associated with a significantly decreased disease risk. The haplotype analysis within the Xeroderma pigmentosum group D (XPD) showed a modest association between two haplotypes and a decrease in melanoma risk. There were no major differences between the prevalence of the XP polymorphisms among young or older patients with melanoma.
There are suggestions in the literature that common variants in the XPD gene may be associated with an altered risk of melanoma and breast cancer. To establish if the XPD common variants Asp312Asn and Lys751Gln are associated with an increased melanoma or breast cancer risk we performed an association study based on genotyping 426 unselected patients with malignant melanoma (MM) and 1830 consecutive breast cancer cases and compared the results to 1262 geographically matched newborns, 621 adults from the region of Szczecin (unselected for age and cancer family history), 421 healthy adults age- and sex-matched with the melanoma cases and 511 healthy controls matched with the breast cancer patients from the region of Szczecin. Additionally we examined the prevalence of three additional XPD variants, Gly156Gly, Leu485Pro and Arg112His amongst the 421 unselected melanoma patients. All of the variants when evaluated singularly were found not to be associated either with melanoma or breast cancer risk in younger or older patients. A modest association was observed with breast cancer risk when the Lys751Gln_CC/Asp312Asn_AA genotype (OR=1.5, p<0.05) segregated together. Individuals harboring the Lys751Gln_CC/Gly156Gly_CC genotype were significantly over-represented among late-onset melanoma cases (OR=1.7, p<0.05). The results of analyses of linkage disequilibrium and haplotype frequency support the thesis that a combination of at least two SNPs (Lys751Gln_CC/Gly156Gly_CC or Lys751Gln_CC/Asp312Asn_AA) inherited as a haplotype was associated with disease. These two pairs of SNPs could therefore be regarded as a single hereditary unit that would have a very small probability of being disrupted by recombination. Additional studies are required to determine whether these particular changes can be associated with an increased risk of other malignancies at different sites of origin.
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