13 research outputs found
Determinación y validación de dianas implicadas en la carcinogénesis del osteosarcoma infantil mediante plataformas de genómica y Proteómica
Screening of the human tumor necrosis factor-alpha (TNF-α) gene promoter polymorphisms by PCR–DGGE analysis
Analysis of the p16INK4 and TP53 tumor suppressor genes in bone sarcoma pediatric patients
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Genome-wide Association Study Identifies Two Susceptibility Loci for Osteosarcoma
Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. In order to better understand the genetic etiology of osteosarcoma, we performed a multi-stage genome-wide association study (GWAS) consisting of 941 cases and 3,291 cancer-free adult controls of European ancestry. Two loci achieved genome-wide significance: rs1906953 at 6p21.3, in the glutamate receptor metabotropic 4 [GRM4] gene (P = 8.1 ×10-9), and rs7591996 and rs10208273 in a gene desert on 2p25.2 (P = 1.0 ×10-8 and 2.9 ×10-7). These two susceptibility loci warrant further exploration to uncover the biological mechanisms underlying susceptibility to osteosarcoma
Association between tumor necrosis factor-alpha promoter polymorphisms and type 2 diabetes and obesity in Chilean elderly women Asociación entre polimorfismos de la región promotora del gen del factor de necrosis tumoral alfa (TNF-alfa) con obesidad y dia
Background : Tumor necrosis factor-alpha (TNF-alpha) has an increased expression in the adipose tissue of obese subjects and is involved in insulin resistance. Aim: To screen for associations between -308G/A, -238G/A, -376G/A and -163G/A genetic variants of the TNF-alpha gene, diabetes and obesity-related variables. Material and methods: A group of 263 elderly women aged 60-90 years were recruited. Among them, an oral glucose tolerance test was performed and serum lipids measured in 100 women. TNF-alpha genotypes were determined by polymerase chain reaction (PCR) and analysis of restriction fragment lenght polymorphisms. Results: No significant differences were found when comparing allele frequencies in TNF-alpha polymorphisms of normal subjects with those having impaired glucose tolerance or type 2 diabetes. After excluding patients with previous diagnosis of diabetes, no significant differences by polymorphism carrier status were found for plasma levels of lipids, glucose and insuli
Detectable clonal mosaicism and its relationship to aging and cancer
10.1038/ng.2270Nature Genetics446651-658NGEN
Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types
BACKGROUND: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. METHODS: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. RESULTS: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. CONCLUSION: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation