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Genome-wide single nucleotide polymorphysm analysis of lung cancer risk detects the KLF6 gen
No full textCancer Lett. 2007 Jun 28;251(2):311-6. Epub 2007 Jan 16.
Genome-wide single nucleotide polymorphism analysis of lung cancer risk detects the KLF6 gene.
Spinola M, Leoni VP, Galvan A, Korsching E, Conti B, Pastorino U, Ravagnani F, Columbano A, Skaug V, Haugen A, Dragani TA.
SourceDepartment of Experimental Oncology and Laboratories, Istituto Nazionale Tumori, Via G. Venezian 1, 20133 Milan, Italy.
Abstract
A genome-wide association analysis using the Affymetrix 100K SNP array was carried out in a case-control study of lung cancer. Allele frequencies were estimated initially in DNA pools. Significant differences in allele frequency detected in the SNP array analysis were first tested in the same DNA pools by pyrosequencing and then by individual genotyping. DNA pooling analysis identified rs10508266 SNP, located approximately 12.5kb from the 5'-end of the KLF6 gene, as a marker showing significant association with lung cancer risk. Since the SNP was in significant linkage disequilibrium with the KLF6 gene region, we analyzed an Italian population of 338 lung adenocarcinoma cases and 335 controls for the possible role of the reported functional rs3750861 SNP, located 15.6kb from the rs10508266 SNP. The rs3750861 affects expression of KLF6 splicing variants in prostate cancer and we found that its rare allele is associated with reduced lung cancer risk (odds ratio, 0.5; 95% CI, 0.3-0.8). A Norwegian replication series of 265 non small cell lung cancer cases, and 356 controls, however, did not confirm the association. In light of the reported functional involvement of the KLF6 gene in lung cancer and in other cancer types and to the functional nature of the rs3750861 SNP, our results suggest a potential involvement of KLF6 polymorphisms in lung cancer risk, although additional studies in large series are needed to confirm our findings and to elucidate the mechanism by which the KLF6 SNPs influence lung cancer risk.
PMID:17223258[PubMed - indexed for MEDLINE
Construction of a phylogenetic tree for inbred strains of rat by arbitrarily primed polymerase chain reaction (AP-PCR).
No full textNegative results of short-term genotoxicity tests with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene
No full textThe phenobarbital-like enzyme inducer and tumor promoter of murine hepatocarcinogenesis, 1,4-bis[2-(3,5-dichloropyridoxy)]benzene has been assayed in short-term genotoxicity tests, i.e, the Salmonella mutagenicity test, micronucleus and chromosomal aberrations analysis in mouse bone marrow cells in vivo, DNA alkaline elution and DNA unwinding assays in mouse liver in vivo. All the assays performed proved negative
Gene expression of pyrogenic cytokines in Hodgkin's disease lymph nodes.
No full textBACKGROUND:
Inflammatory cytokines released by either the neoplastic or reactive cells in Hodgkin's disease (HD) might mediate its peculiar clinical and histopathological features. We investigated by Northern blotting the gene expressions of the pyrogenic and inflammation-associated cytokines IL-1 alpha, IL-1 beta, TNF-alpha, TNF-beta (lymphotoxin) and IL-6 in 14 HD lymph nodes and studied their relation to systemic symptoms (B symptoms).
METHODS:
Two ug of poly(A)+RNA from 14 HD lymph nodes (8 from symptomatic and 6 from asymptomatic patients, of different histological type and disease stage) were subjected to agarose electrophoresis, Northern blotted and hybridized to the various cytokine cDNA probes.
RESULTS:
The inflammatory cytokines were expressed very heterogenously in HD, even in lymph nodes with the same histological type and with similar stromal inflammatory reactions. IL-1 beta was increased about 2 to 10 times in 5 of 8 lymph nodes from patients with B symptoms, whereas the other cytokines were heterogenously expressed in both symptomatic and asymptomatic patients. Statistical analysis on densitometric values demonstrated that the difference in IL-1 beta expression between symptomatic and asymptomatic patients was significant (p less than 0.02).
CONCLUSIONS:
These results support the hypothesis of increased IL-1 levels in tumoral lymph nodes from symptomatic HD patients
THE BN RAT STRAIN CARRIES DOMINANT HEPATOCARCINOGEN RESISTANCE LOCI
No full textThe phylogenetically distant F344 and BN rat strains and their (BN x F344) F1 hybrids were compared for susceptibility to hepatocarcinogenesis using the 'resistant hepatocyte' model. Quantitative stereological analysis of frequency (number/liver) and size (mean volume and volume fraction) of placental form glutathione S-transferase (GST-P)-positive lesions was carried out at 8, 15 and 32 weeks after diethylnitrosamine initiation. The number/liver of GST-P-positive lesions at any time point was slightly higher in BN and (BN x F344) F1 rats than in F344 rats, but not statistically different. However, mean volume and volume fraction of GST-P positive lesions were much higher in F344 than in both BN and (BN x F344) F1 rats at any time point, with a difference of up to > 10-fold. GST-P-positive lesions exhibited a significantly higher labeling index and much lower remodeling in male F344 than in BN and (BN x F344) F1 rats. HCCs were present at 54-57 weeks after initiation in 77% of male F344 and in no (BN x F344) F1 rats and at 70 weeks HCCs were observed in 100% of male F344 and in 23% of (BN x F344) F1 rats. These results suggest that the BN rat strain is resistant to hepatocarcinogenesis and that its resistance is genetically transmitted as a dominant character to F1 hybrids of the BN strain with the F344 susceptible strain
Stearoyl-CoA desaturase 1 (Scd1) gene overexpression is associated with genetic predisposition to hepatocarcinogenesis in mice and rats
No full textThe stearoyl-CoA desaturase 1 (Scd1) gene is involved in
the synthesis and regulation of unsaturated fatty acids. Its
expression is increased by several treatments/conditions
that are associated with hepatocarcinogenesis (peroxisome
proliferators, iron overload, dichloroacetic acid). We found
that the Scd1 gene is differentially expressed, showing
10-fold higher mRNA levels in the normal liver tissue of
C3H/He mice, which are genetically susceptible to hepatocarcinogenesis,
than of BALB/c mice, which are resistant.
Similarly, Scd1 mRNA expression was ~4-fold higher in
the normal liver of F344 rats, which are susceptible to
hepatocarcinogenesis, than in Brown Norway (BN) rats,
which are resistant. The chromosomal location of the Scd1
locus, both in mice and rats, excludes Scd1 candidacy as a
hepatocellular tumor-modifier gene, as the Scd1 locus
did not show allele-specific effects in a BALB/cC3H/He
intercross or in a BNF344 backcross and intercross. No
Scd1 coding polymorphisms were detected in the mouse
and the rat strains showing elevated Scd1 expression. These
results suggest that the Scd1 gene represents a downstream
target of hepatocellular tumor-modifier loci in two rodent
species
GENETIC-MAPPING AND EXPRESSION ANALYSIS OF THE MURINE DNA-LIGASE-I GENE
No full textWe mapped the murine DNA ligase I gene (Lig1) in the mouse genome by using a mapping panel from an interspecific cross. Lig1 mapped to a centromeric part of chromosome 7, a region homologous to human chromosome 19q, where the human homologue LIG1 was localized. In addition, Lig1 expression was analyzed during the course of mouse liver-cell regeneration induced by partial hepatectomy, necrogenic doses of carbon tetrachloride, or the mitogen 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene. The results demonstrate that Lig1 is expressed in the liver during active cell proliferation. (C) 1995 Wiley-Liss, Inc
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