Association of Genetic Polymorphisms of GREM1 Gene with Susceptibility to Non-Syndromic Cleft Lip with or without Cleft Palate in an Iranian Population.

Background: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is common congenital birth anomaly with multifactorial etiology. The GREM1 gene has been proposed to play a role in oral clefts development.Objective: The aim of the present study was to evaluate the correlation between GREM1 polymorphisms and the risk of NSCL/P in an Iranian population.Methods: Genotyping of rs7162202, rs12915554, rs3743105, rs1129456, and rs10318 polymorphisms of GREM1 gene in 150 NSCL/P and 152 healthy subjects was determined by the PCR-RFLP or T-ARMS-PCR.Results: The findings showed that the rs12915554 variant significantly increased the risk of NSCL/P in heterozygous (OR = 4.20, 95%CI = 2.46-7.11, p < 0.0001, AC vs AA), and allele (OR = 3.17, 95%CI = 2.00-5.08, p < 0.0001, C vs A) genetic models. The rs3743105 polymorphism was correlated with reduced risk of NSCL/P in heterozygous (OR = 0.49, 95%CI = 0.29-0.83, p = 0.008, AG vs GG) and dominant (OR = 0.54, 95%CI = 0.33-0.89, p = 0.018, GA + AA vs GG) genetic models. The rs1129456 variant was positively associated with the risk of NSCL/P in heterozygous (OR = 2.91, 95%CI = 1.12-7.38, p = 0.028, AT vs AA) and allele (OR = 2.80, 95%CI = 2.80-6.95, p = 0.031, T vs C). The rs10318 polymorphism significantly reduced NSCL/P risk in homozygous (OR = 0.20, 95%CI = 0.06-0.67, p = 0.013, TT vs CC), dominant (OR = 0.57, 95%CI = 0.36-0.91, p = 0.019, CT + CC vs CC), recessive (OR = 0.24, 95%CI = 0.07-0.76, p = 0.031, TT vs CT + CC), and allele (OR = 0.57, 95%CI = 0.38-0.84, p = 0.005, T vs C). No correlation was observed between rs7162202 polymorphism and NSCL/P.Conclusion: The findings support that GREM1 polymorphisms are involved in NSCL/P susceptibility in an Iranian population.

Cell free circulating tumor nucleic acids, a revolution in personalized cancer medicine.

Innovative diagnostics are becoming an essential component in personalized cancer medicine. These diagnostics are increasingly based on cell-free nucleic acids and membrane vesicles. Isolating and sequencing cell free circulating DNA (cfDNA) in plasma may progressively substitute tumor biopsies. A small albeit now detectable fraction of cfDNA correspond to circulating tumor DNA (ctDNA). In this review, we describe the pre-analytical procedures for collecting ctDNA from plasma, since these procedures should be optimized within laboratories depending on the available infrastructures. We also provide an overview of the technological breakthrough in ctDNA Isolation for instance digital PCR methods and next generation sequencing techniques and discuss their key challenges. The clinical implementations of liquid biopsy and more specifically ctDNA in cancer management are reviewed. We predict in the near future, ctDNA will be used more routinely to guide cancer treatment and provide a new approach to personalize treatment in precision medicine.