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.

PTCH1 gene variants rs357564, rs2236405, rs2297086 and rs41313327, mRNA and tissue expression in basal cell carcinoma patients from Western Mexico

“…Finally, the genotyping of the rs41313327 (C > T) demonstrated the prevalence of the homozygous genotype for the wild allele (C/C), following the frequencies reported in databases and even with previous investigations, in which patients with clinical conditions—other than cancer—had a similar frequency of the C allele to our studied groups, where the presence of the minor allele (T) was not detected either 46 . However, previous studies in BCC patients from the Polish population reported the frequencies of the C/C, C/T, and T/T genotypes with no differences between patients and controls 24 …”

“…46 However, previous studies in BCC patients from the Polish population reported the frequencies of the C/C, C/T, and T/T genotypes with no differences between patients and controls. 24 We also investigate a possible pathogenic effect in PROVEAN, SIFT, Polyphen, and FATHMM due to aminoacid change for exonic variants rs357564, rs2236405, and rs41313327 or splicing effect of intronic variant rs2297086 in regSNP-intron and Human Splicing Finder. [47][48][49][50][51][52] Although it was not conclusive, we could presume that the rs357564 may have a deleterious effect as we consider that the c-terminal domain is related to SMO protein retention.…”

“…[20][21][22][23] For the rs2297086, rs2236405, and rs41313327 few reports have been published. However, the rs2297086 and rs41313327 have been studied in BCC, 20,24 and the rs2236405 in reproductive cancers and congenital diseases. 25,26 Previous studies about PTCH1 mRNA and protein expression have reported wide differences in expression levels among diverse types of cancer and tissues.…”

PTCH1 Gene Variants, mRNA Expression, and Bioinformatics Insights in Mexican Cutaneous Squamous Cell Carcinoma Patients

“…One previous analysis of patients with non-cancerous conditions in a Turkish population did not reveal the existence of the minor allele (T) [ 23 ]. In another previous report in a Polish population of patients with BCC, the C/C, C/T, and T/T genotypes were found, although without statistically significant differences between the patients and controls [ 60 ]. Similarly, the minor allele (A) of the rs2236405 variant has been documented with a low frequency, consistent with our results, in which the A allele was only identified in a few heterozygotes (T/A).…”

Identification of critically carcinogenesis-related genes in basal cell carcinoma

“…To date, several signaling pathways and molecules have been demonstrated to be involved in the tumorigenesis and progression of BCC at the molecular level, such as the hedgehog signaling pathway. 4 Genes included in this pathway, such as the hedgehog receptors patched (PTCH1) or smoothened (SMO), have been extensively studied. 5 , 6 Mutations in these genes may cause constitutive hedgehog pathway activation, which promote the development of BCC.…”