Gene expression in response to ionizing radiation and family history of gastric cancer.
Genes and molecular pathways involved in familial clustering of gastric cancer have not yet been identified. The purpose of the present study was to investigate gene expression changes in response to a cellular stress, and its link with a positive family history for this neoplasia. To this aim leukocytes of healthy first-degree relatives of gastric cancer patients and controls were challenged in vitro with ionizing radiation and gene expression evaluated 4 h later on microarrays with 1,800 cancer-related genes. Eight genes, mainly involved in signal transduction and cell cycle regulation, were differentially expressed in healthy relatives of gastric cancer cases. Functional class scoring by Gene Ontology classification highlighted two G-protein related pathways, implicated in the proliferation of neoplastic tissue, which were differentially expressed in healthy subjects with positive family history of gastric cancer. The relative expression of 84 genes related to these pathways was examined using the SYBR green-based quantitative real-time PCR. The results confirmed the indication of an involvement of G-protein coupled receptor pathways in GC familiarity provided by microarray analysis. This study indicates a possible association between familiarity for gastric cancer and altered transcriptional response to ionizing radiation.
Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy. francesca.marcon@iss.it.
Francesca
F
Marcon
Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
Francesco
F
Silvestrini
Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
Ester
E
Siniscalchi
Molecular and Nutritional Epidemiology Unit, ISPO-Cancer Prevention and Research Institute, Via Cosimo il Vecchio 2, 50139, Florence, Italy.
Domenico
D
Palli
Molecular and Nutritional Epidemiology Unit, ISPO-Cancer Prevention and Research Institute, Via Cosimo il Vecchio 2, 50139, Florence, Italy.
Calogero
C
Saieva
Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
Riccardo
R
Crebelli
D000368:Aged; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005192:Family Health; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000528:radiation effects*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007962:Leukocytes / Q000502:physiology / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011839:Radiation, Ionizing; D013274:Stomach Neoplasms / Q000235:genetics*