Palomba G.,CNR Institute of Biomolecular Chemistry |
Colombino M.,CNR Institute of Biomolecular Chemistry |
Contu A.,Servizio Oncologia |
Massidda B.,University of Cagliari |
And 11 more authors.
Journal of Translational Medicine | Year: 2012
Background: Role of KRAS, BRAF and PIK3CA mutations in pathogenesis of colorectal cancer (CRC) has been recently investigated worldwide. In this population-based study, we evaluated the incidence rates and distribution of such somatic mutations in genetically isolated population from Sardinia.Methods: From April 2009 to July 2011, formalin-fixed paraffin-embedded tissues (N = 478) were prospectively collected from Sardinian CRC patients at clinics across the entire island. Genomic DNA was isolated from tissue sections and screened for mutations in KRAS, BRAF, and PIK3CA genes by automated DNA sequencing.Results: Overall, KRAS tumour mutation rate was 30% (145/478 positive cases). Distribution of mutation carriers was surprisingly different within the island: 87/204 (43%) in North Sardinia vs. 58/274 (21%) in Middle-South Sardinia (p<0.001). Among 384 CRC cases whose DNA was available, only one (0.3%) patient carried a mutation in BRAF gene; PIK3CA was found mutated in 67 (17%) patients. A significant inverse distribution of PIK3CA mutation rates was observed within Sardinian population: 19/183 (10%) cases from northern vs. 48/201 (24%) cases from central-southern island (p<0.001). This heterogeneity in frequencies of KRAS/PIK3CA somatic mutations is consistent with already-reported discrepancies in distribution of germline mutations for other malignancies within Sardinian population. Preliminary clinical evaluation of 118 KRAS wild-type patients undergoing anti-EGFR-based treatment indicated lack of role for PIK3CA in predicting response to therapy.Conclusions: Our findings support the hypothesis that differences in patients' origins and related genetic backgrounds may contribute to even determine the incidence rate of somatic mutations in candidate cancer genes. © 2012 Palomba et al.; licensee BioMed Central Ltd.
Marcon A.,Azienda USL di Ravenna e in Friuli Venezia Giulia |
Accorsi A.,Servizio Epidemiologia |
Di Tommaso F.,Servizio Epidemiologia |
Falasca P.,Servizio Epidemiologia |
And 2 more authors.
Giornale di Gerontologia | Year: 2010
Objective. The aim of our study is to identify how the concept of frailty has been described in medical and psycho-social literature, analyzing also analogies and/or differences. Methods. In order to investigate the words associated to frailty, abstracts published in PsycInfo and PubMed from 1983 to 2009 were examined using T-Lab Multilingual software. 1539 abstracts, that contain (frail* old*) OR (frail* elder*) in the title, were analyzed. Results. In medical abstracts (PubMed), frailty is frequently associated with words regarding clinical decline and disability. In psycho-social abstracts (PsycInfo), frailty is also defined as a natural phase of life with specific skills and resources.