BACKGROUND:The phenotypic variability in cystic fibrosis (CF) is widely recognized and modulated by environmental and genetic factors, including CFTR pathogenic variants and modifier genes genetic variants. In this context, determining the presence of variants in genes involved in immune response may allow a better understanding of CF variability, mainly in lung disease. Thus, ADIPOQ and STATH genes were selected and the analysis of exons and exon/intron junctions was performed for the determination of variations in its sequence, to determine the possible genetic modulation.METHODS:A total of 49 patients with CF, diagnosed for showing abnormal [chloride] levels in the sweat test, and identification of two pathogenic variants in CFTR categorized as class I and II were included. Genetic sequencing was performed for the identification of variants in the modifier genes.RESULTS:In our analysis, there was absence of rare genetic variants in STATH and ADIPOQ genes associated with the clinical variability. Thus, we are not able to establish an association between the disease severity and rare genetic variants in STATH and ADIPOQ genes, considering exons and exon/intron junctions.CONCLUSIONS:Considering the negative screening for rare genetic variants in ADIPOQ and STATH genes, it may be concluded that these genes are not associated with phenotypic modulation of CF in our population. To understand the modifier genes and its action at CF variability it is essential to promote a better overview of the disease. Also, negative reports can help to direct new studies without the use of unnecessary financial support.

Radiological tools are critical for monitoring cystic fibrosis (CF) patients’ thoracic, abdominal, rhinosinusal, and bone systems. Given the likelihood of increasing demand for ionizing techniques for research purposes, we sought to determine how clinicians use radiological tools in their centers. Methods: A 39-item questionnaire was sent to 49 pediatric and adult CF centers in July 2011. Questions were asked on frequency and indications for thoracic, abdominal, rhinosinusal, and bone imaging, as well as the radiological devices available. Results: Thirty-three of 49 (68%) centers answered the questionnaire. Among them, 36% were pediatric centers, 33% mixed, and 31% adult centers. An annual chest x-ray was done routinely in more than 95% of centers, starting at the initial stage of the disease (neonatal screening). While adult clinicians did not routinely perform chest CT, 72% of the pediatricians requested it routinely. Pediatricians declared doing the first chest CT at a mean of 4.9±1.2 years of age, and every 2 or 3 years thereafter. Respectively, 32% and 20% of pediatric and adult centers regularly indicated the cumulative doses received by patients on medical charts. MRI was used in seven out of 33 centers mainly for abdominal indications. Annual chest x-ray is part of routine follow-up for most centers; however, divergent attitudes have emerged regarding chest CT use between pediatric and adult centers. The reasons for the routine use of chest CT in pediatric patients will need further investigations. Furthermore, efforts should be made by clinicians to regularly monitored cumulative doses received by their patients, particularly in the pediatric population.

Background: The complete medical approach to colorectal cancer often includes not only the treatment of the individual who is sick, but also requires the study of his family, as cancer is eventually linked to some kind of inherited genetic mutation. It is, therefore, very important to completely understand the epidemiology and the genetic aspects of this type of cancer, in order to successfully assist the patient and his family. This study aims to investigate the incidence of colorectal cancer associated to inherited mutations, classifying them, based on the guidelines of the Brazilian Clinical Genetics Society (BCGS), into three categories: Hereditary (inherited mutations that can lead directly to cancer), Familial (inherited mutations that can predispose to secondary oncogenic mutations) and Sporadic (related to non-inherited mutations). Methods: This research was made based on data collected from 291 patients attended between the years of 2006 and 2011 at the State University of Campinas' oncology service. Data gathered include several of the patient's characteristics, such as age at the diagnosis and familial history related to cancer, as well as tumor related information, such as stage of the tumor and pathological findings. This data was analyzed accordingly to the BCGS guidelines and Amsterdam I and II criteria, aiming to determine the role of genetics in each of the 291 cases. Results: 14% of the patients could not be assigned to one of the three categories, because they alone met the Amsterdam criteria for hereditary cancer, but their family did not present, at the time, positive cancer history. 6,5% of the patients were qualified to hereditary colorectal cancer, while 2,5% of them met the criteria for familial colorectal cancer. The rest of the patients (77%) were assigned to the sporadic colorectal cancer group. Conclusion: The amount of individuals with colorectal cancer related to inherited mutations indicates that inheritance does not ensure colorectal cancer manifestation, but cannot be ignored. Further research is needed to point out what's precisely the inherited mutations role in colorectal cancer. This research also shows that it's important to provide proper genetic testing for individuals who are suspected to have a hereditary/familial colorectal cancer, but do not meet all the criteria for the diagnosis, after all, they represent an important share of the total analyzed (14%).

Objectives: Ecological relationships between bacteria in communities may contribute to disease progression. Our aim was to compare bacterial community structures in CF airways and the upper airways of healthy volunteers as a surrogate for a healthy lung microbiome. Methods: CF sputum samples (analysed by pyrosequencing) were compared with samples from 9 sites in the upper airways (Human Microbiome Project; suband supragingival-plaque, saliva, buccal mucosa, hard palete, keratinised gingiva, tongue dorsum, tonsils and throat). Normalised data for each cohort was analysed for occupancy and relative abundance of different taxa. Significance of bacterial cooccurrence was determined using Spearman’s Ranked Correlation Coefficient with a cut-off of >0.5 (p< 0.001). Results: Preliminary analysis demonstrates a “core” community with members of the genera Streptococcus, Actinomyces, Fusobacterium, Gemella, Granulicatella, Neisseria, Prevotella, Rothia and Veillonella the most frequently detected and abundant taxa, irrespective of host state. There was an increased prevalence of Pseudomonas and Burkholderia species in CF airways. Furthermore, a significant co-occurrence was detected between a number of the “core” taxa, which formed sub-networks within the overall community structure. Conclusion: A “core” microbial community is distributed throughout the airways. Due to a lack of resolution in short-read sequence data, it is difficult to assess if a shift within the “core” taxa at the species level contributes to disease progression. Further detailed analysis of interand intra community architecture is on-going to confirm these findings. WS8.6 Interaction of microorganisms modulating the cystic fibrosis clinical severity F.A. Marson1,2, C.S. Bertuzzo1, C.E. Levy2, A.F. Ribeiro2, J.D. Ribeiro2. 1Unicamp, Genetics, Campinas, Brazil; 2Unicamp, Pediatrics, Campinas, Brazil

Achromobacter xylosoxidans is a non-glicose-fermenting environmental Gramnegative rod with increasing recovering frequency from the respiratory tract of Cystic Fibrosis (CF) patients.The pathogenic role of this microorganism is still unclear including the knowledge of its virulence factors.We are searching for potencial virulence factors in A. xylosoxidans strains isolated from CF pediatric patients seen at the outpatient reference center at our State University Hospital.The strains were identified by conventional tests, by automated Vitek II ® and controlled with LMG ® reference strains and by PCR.The culture supernatants in BHI of 10 different clinical isolates of A. xylosoxidans and the LMG 1863 strain were assayed for cytotoxic activity.Cytotoxic activity was observed only in H-460 (human lung carcinoma), inducing blebbings and cellular death after 18 hours assays for all strains.Microscopic analysis revealed rounding and membrane alterations followed by detachment and cellular death.However no cytotoxic activity was verified on HeLa (human cervix carcinoma), 3T3 (mouse fibroblast) and Vero (green monkey kidney) cells.These results suggest that the cytotoxic activity of A. xylosoxidans to human lung cells (H-460) could be a potencial mechanism of pathogenicity that may participate in the process of lung parenchyma destruction in cystic fibrosis patients and should be better investigated.