RESUMO
AIM: Colorectal cancer (CRC) is one of the most common cancers worldwide and, although the majority of cases are sporadic, its development and progression depends on a range of factors: environmental, genetic and epigenetic. A variety of genetic pathways have been described as being crucial in CRC, including protein tyrosine phosphatases (PTPs). PTPN13 (also called FAP-1) is a non-receptor PTP and interacts with a number of important components of growth and apoptosis pathways. It is also involved in the inhibition of Fas-induced apoptosis. METHOD: The single nucleotide polymorphism genotype at Y2081D (T>G) (rs989902) of PTPN13 exon 39 was determined in DNA extracted from blood samples from 174 sporadic CRC patients and 176 healthy individuals. Also, a meta-analysis was performed based on three articles accessed via the PubMed and ResearchGate databases. RESULTS: The risk of CRC was 2.087 times greater for patients with the GG genotype than for those with the TT genotype (P = 0.0475). In the meta-analysis, a significantly increased risk of cancer associated with the G allele was observed in the squamous cell carcinoma of the head and neck subgroup (TT vs GG+GT, OR 1.23, 95% CI [1.02, 1.47], P = 0.0258), and a significantly decreased risk in the breast cancer subgroup (TT vs GG+GT, OR 0.63, 95% CI [0.41, 0.96], P = 0.0334) and in the CRC subgroup (GT+TT vs GG, OR 0.51, 95% CI [0.41, 0.95], P = 0.0333). CONCLUSION: PTPN13 rs989902 is significantly associated with the risk of CRC in the Polish population. Given that this report provides the first evidence of an association of PTPN13 rs989902 with the risk of CRC in a Caucasian population, further large scale studies are necessary to confirm this finding.
Assuntos
Neoplasias Colorretais/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Proteína Tirosina Fosfatase não Receptora Tipo 13/genética , População Branca/genética , Idoso , Carcinoma de Células Escamosas/genética , Estudos de Casos e Controles , Neoplasias Colorretais/sangue , Éxons , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polônia , Proteína Tirosina Fosfatase não Receptora Tipo 13/sangue , Fatores de RiscoRESUMO
Esophageal atresia (EA) is a congenital developmental defect of the alimentary tract concerning the interruption of the esophagus with or without connection to the trachea. The incidence of EA is 1 in 3000-3500 of live-born infants, and occurs in both isolated and syndromic (in combination with abnormalities in other organ systems) forms. The molecular mechanisms underlying the development of EA are poorly understood. Knockout studies in mice indicate that genes like Sonic hedgehog, Gli2, and Gli3 play a role in the etiology of EA. These facts led us to hypothesize that Sonic hedgehog-GLI gene rearrangements are associated with EA in humans. To test this hypothesis, we screened patients with isolated and syndromic EA for GLI2 and/or GLI3 microrearrangements using methods to estimate the copy number (Multiplex Ligation-dependent Probe Amplification, real-time polymerase chain reaction). To our best knowledge this is the first study assessing copy number of GLI2 and GLI3 genes in patients with EA.
