title: Relation between sonic hedgehog pathway gene polymorphisms and basal cell carcinoma development in the Polish population.
abstract: In recent decades, increases have been observed in the incidence of nonmelanoma skin cancers, including basal cell carcinoma (BCC) and squamous cell carcinoma. BCC is the most common neoplasm in Caucasian populations. Sonic hedgehog (Shh) pathway impairment plays a key role in BCC pathogenesis, and there is evidence that Shh pathway genetic variations may predispose to BCC development. We genotyped 22 single-nucleotide polymorphisms (SNPs) in 4 Shh pathway genes: SHH, GLI, SMO, and PTCH. The study group consisted of 142 BCC patients and 142 age-matched, sex-matched healthy subjects (controls). SNPs were assessed using the PCR-RFLP method. The genotype distribution for the polymorphisms in the rs104894049 331 A/T SHH, rs104894040 349 T/C SHH, and rs41303402 385 G/A SMO genes differed significantly between the BCC patients and the controls. The presence of CC genotype in the SHH rs104894040 349 T/C polymorphism was linked to the highest risk of BCC development (OR 87.9, p < 0.001). Other genotypes, such as the TT in SHH rs104894049 331 A/T and the GG in SMO rs41303402 385 G/A also statistically raised the risk of BCC, but these associations were weaker. Other investigated polymorphisms showed no statistical differences between patients and controls. The results obtained testify to the importance of the SHH and SMO gene polymorphisms in skin cancerogenesis. These results mainly underline the potential role of SHH3 rs104894040 349 T/C gene polymorphism in the development of skin basal cell carcinomas in patients of Polish origin.
authors.affiliation: Department of Dermatology, Medical University of Lodz, Plac Hallera 1, 90-647, Lodz, Poland. lesiak_ola@interia.pl.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Lesiak
authors.affiliation: Department of Dermatology, Medical University of Lodz, Plac Hallera 1, 90-647, Lodz, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Sobolewska-Sztychny
authors.affiliation: Division of Internal Medicine, Asthma and Allergy, Medical University of Lodz, Lodz, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Majak
authors.affiliation: Department of Dermatology Venereology and Allergology, Medical University of Gdansk, Gdańsk, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Sobjanek
authors.affiliation: Department of Experimental Immunology, Medical University of Lodz, Lodz, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Wodz
authors.affiliation: Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Lodz, Poland.
authors.forename: Karolina Przybyłowska-
authors.initials: KP
authors.lastname: Sygut
authors.affiliation: Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Lodz, Poland.
authors.forename: Ireneusz
authors.initials: I
authors.lastname: Majsterek
authors.affiliation: Department of Dermatology, Medical University of Lodz, Plac Hallera 1, 90-647, Lodz, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Wozniacka
authors.affiliation: Department of Dermatology, Medical University of Lodz, Plac Hallera 1, 90-647, Lodz, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Narbutt
mesh_terms: D000328:Adult; D000368:Aged; D002280:Basal Cell Carcinoma / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D053823:Hedgehog Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011044:Poland; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics*; D000072086:Smoothened Receptor; D014157:Transcription Factors / Q000235:genetics*; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C509239:SHH protein, human; C491023:SMO protein, human; D000072086:Smoothened Receptor; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1
keywords: Basal cell carcinoma; GLI; PTCH; Polymorphisms; SHH; SMO; Sonic hedgehog pathway