title: Potential association of single nucleotide polymorphisms in pigmentation genes with the development of basal cell carcinoma.
abstract: The risk of developing skin cancers is dependent on a combination of environmental factors and personal genetic predispositions. Basal cell carcinoma (BCC) has been associated with single nucleotide polymorphisms in several pigmentation genes; however, there is still controversy concerning the mechanism by which these variants may increase the risk of BCC. The pathway may lead to pigmentation alone, but evidence for their independent influence is growing. Using a single base extension protocol, candidate polymorphisms within 11 known pigment-related genes were studied for their association with BCC in a population sample consisting of 164 patients and 707 controls. The significance of variation within the MC1R gene was confirmed and, in addition, position rs12203592 within the IRF4 gene was shown to be associated with BCC. These associations remained significant after adjustment for skin color. Gene-gene interactions were found to influence susceptibility to BCC. Among interacting genes are the two above-mentioned loci with main effect on BCC risk and additionally KITLG, TYRP1, ASIP and TYR. The obtained results indicate that polymorphism at MC1R and IRF4 constitute pigmentation-independent risk factor in the development of BCC. Moreover, susceptibility to BCC may be influenced by epistatic effects between pigmentation genes.
authors.affiliation: Department of Dermatology, Collegium Medicum of the Jagiellonian University, Kraków, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kosiniak-Kamysz
authors.forename: Ewelina
authors.initials: E
authors.lastname: Pośpiech
authors.forename: Anna
authors.initials: A
authors.lastname: Wojas-Pelc
authors.forename: Magdalena
authors.initials: M
authors.lastname: Marcińska
authors.forename: Wojciech
authors.initials: W
authors.lastname: Branicki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054366:Agouti Signaling Protein / Q000235:genetics; D002280:Basal Cell Carcinoma / Q000453:epidemiology / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D056726:Genetic Association Studies / Q000706:statistics & numerical data*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D050835:Interferon Regulatory Factors / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D010088:Oxidoreductases / Q000235:genetics; D011044:Poland / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics; D012306:Risk; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012880:Skin Pigmentation / Q000235:genetics*; D019089:Stem Cell Factor / Q000235:genetics; D055815:Young Adult; D000099218:Interferon Regulatory Factor-4
chemical_list: D054366:Agouti Signaling Protein; D050835:Interferon Regulatory Factors; D008562:Membrane Glycoproteins; D010088:Oxidoreductases; D044102:Receptor, Melanocortin, Type 1; D019089:Stem Cell Factor; D000099218:Interferon Regulatory Factor-4; C515182:ASIP protein, human; C489799:TYRP1 protein, human