A collaborative group of investigators has joined together to identify five genetic variations associated with Crohn’s disease (CD) and Jewish individuals of Eastern and Central European descent, who are also known as Ashkenazi Jews.
CD causes inflammation of the lining of the digestive tract and can be both painful and debilitating, and sometimes may lead to life-threatening complications. CD is two-to-four times more prevalent among individuals of Ashkenazi Jewish descent compared to non-Jewish Europeans. The study conducted at multiple institutions across the world, including the Feinstein Institute for Medical Research, was an important step toward understanding the genetic reasons for this higher prevalence.
‘This large collaborative study made it possible to define more precisely the genetic contributions to Crohn’s disease that are enriched in the Ashkenazi Jewish population, which has carried a higher risk for this disorder.’ said Peter K. Gregersen, head of the Robert S. Boas Center for Genomics and Human Genetics at the Feinstein Institute. ‘The study identified genetic regions that hadn’t been discovered before, and if additional studies of these regions are conducted there is a chance that biological pathways affecting susceptibility to Crohn’s disease could be found and novel treatments could be developed.’
Seventy-one genetic variants had already been identified in patients who had Crohn’s disease (CD) and were of European descent. A collaborative group of investigators, including some from the Feinstein Institute for Medical Research, led by Inga Peter at Mt Sinai School of Medicine took a step further and conducted a genome-wide association study (GWAS) aimed at exploring genetic variation associated with CD in Jewish individuals of Eastern and Central European decent (Ashkenazi Jews). The study was conducted by combining raw genotype data across 10 Ashkenazi Jew cohorts consisting of 907 cases and 2,345 controls in the discovery stage followed up by a replication study in 971 cases and 2,124 controls. The study confirmed 12 of the known variants and identified five novel genetic varation regions not previously found. These five novel genetic regions were mapped to chromosomes 5q21.1, 2p15, 8q21.1, 10q26.3, and 11q12.1. The Feinstein Institute

Lung cancer is the number one cancer killer, and it’s often discovered too late to cure. But researchers at National Jewish Health in Denver may have found a new way to spot it earlier than ever.
A new study at National Jewish Health uses breath to detect the disease.
Years ago Tess detected breast cancer. Her big furry Newfoundland sniffed her owner’s chest enough to make her get a mammogram and she was diagnosed.
‘We know that they can smell more than what you or I can smell,’ Dr. James Jett with National Jewish Health said.
Now man is experimenting with a machine. Call it a mechanical dog.
‘There’s no pins and needles associated with it; no blood draw, it’s painless,’ Jett said.
Researchers at the hospital demonstrated the device to 4 On Your Side Health Specialist Kathy Walsh. It looks like a computer with a hose attached. A person breathes in and out of the hose for about five minutes. The breath is pulled across 128 sensors that can detect different chemicals.
‘The goal is to see if we can come up with a certain pattern of chemicals in your breath that says you’re at a high likelihood of having cancer or that says you do have cancer,’ Jett said.
About 80 percent of lung cancer patients are now diagnosed in advanced stages.
‘If we can detect more people with earlier stage cancer we’re going to have a better chance of curing more individuals,’ Jett said.
The breath test is easy and will be inexpensive, but the study will take a number of years.
Researchers say, like a dog, the new sensor still needs to be trained to make sure it’s got a nose for accurate diagnosis. CBS

Personalised prognostic tools and gene-based therapies may improve the survival and quality of life of patients suffering from glioblastoma, an aggressive and deadly form of brain cancer, reports a new University of Illinois study funded by the NIH National Cancer Institute.
‘We confirmed known biomarkers of glioblastoma survival and discovered new general and clinical-dependent gene profiles,’ said Nicola Serao, a U of I Ph.D. candidate in animal sciences with a focus in statistical genomics. ‘We were able to compare biomarkers across three glioblastoma phases that helped us gain insight into the roles of genes associated with cancer survival.’
Glioblastoma is a complex, multifactorial disease that has swift and devastating consequences, Serao said. Although some genes have been associated with the presence of glioblastoma, few have been identified as prognostic biomarkers of glioblastoma survival and fewer have been confirmed in independent reports.
‘You can’t just find one gene that is related to this cancer and fix it,’ he said. ‘This is one of the aspects of our research that makes it unique. We were able to look at several genes at the same time and relate our findings to this cancer.’
Using genomic information from more than 22,000 genes, Serao took this huge piece of information and began slicing away at it, one gene at a time, until he ended up with a group of genes related to brain cancer.
He studied different survival variables, including length of survival from birth to death, from diagnosis to death, and from diagnosis to progression of the cancer.
‘We studied different variables, but they were complementary, and allowed us to learn more about those genes,’ he said. ‘We understand that some genes have much more impact in cancer than others. And we also discovered that some genes only appeared in one variable, so they were specific for a given phase of cancer.’
This study not only evaluated genes influencing survival, but also took into consideration clinical factors such as age, race and gender.
‘Our research suggests you can’t treat all patients the same,’ Serao said. ‘For example, we found gene expression patterns that have different, and sometimes opposite, relationships with survival in males and females and concluded that treatments affecting these genes will not be equally effective. Personalised therapy dependent on gender, race and age is something that is possible today with our advanced genomic tools.’
Recognising that genes seldom act alone, this team of researchers took several genes into consideration at the same time and uncovered networks of genes related to glioblastoma survival.
Sandra Rodriguez Zas, co-researcher and U of I professor of animal science and bioinformatics, said they looked at commonalities between the genes linked to glioblastoma survival and progression, too.
‘If a large number of genes linked to survival belong to a particular pathway, this pathway is considered enriched,’ Rodriguez Zas said. ‘Depending on whether the pathway and genes have tumour suppressor or oncogenic characteristics, we should be able to use that information to support or attack that pathway with targeted therapies.’
Gaining a deeper understanding of the biological meaning, or roles, for these genes will provide researchers with even more ammunition to fight this deadly form of brain cancer.
‘Because of the innovative approach we used, we believe we can more confidently predict whether a patient will have a shorter or longer survival rate and select the most adequate therapies,’ she said.
Illinois. University of Illinois College of Agricultural, Consumer and Environmental Sciences

Certain proteins, such as 14-3-3, conserve their basic functions of cell cycle control in diverse organisms, from worms to humans. In a study led by Julián Cerón and Simó Schwartz Jr, researchers from the Bellvitge Biomedical Research Institute (IDIBELL) and the Research Institute of Vall d’Hebron (VHIR) respectively, have described germ line functions of par-5, which is one of the two 14-3-3 proteins existing in Caenorhabditis elegans, worms used as experimental model in genetic studies. The overexpression of the 14-3-3 proteins is related to the resistance of tumours to chemotherapy, which could have implications for clinical practice.
Researchers found that par-5 gene, as its human homologues, is required for DNA damage response in C. Elegans validating the model to investigate chemotherapies and genetic modifications since 14-3-3 proteins are therapeutic targets in cancer
The powerful genetic tools of C. elegans have allowed a precise functional dissection of the single 14-3-3 protein present in their germline. The researchers have discovered that par-5 is not only necessary for proper cell cycle regulation, but also to prevent the accumulation of endogenous DNA damage and genomic instability.
Moreover, this study reveals that par-5 is required for DNA repair response when it is damaged by chemicals or ionizing radiation. In such response, the researchers propose a model where PAR-5 regulates CDK-1 phosphorylation to stop the cell cycle and repair the damage induced by chemotherapeutic agents.
The overexpression of the 14-3-3 protein has been related to chemotherapy resistance in cancer cell lines while its downregulation sensitises cells to therapy-induced cell death. Therefore, this study in C. elegans provides the basis for a model to study chemotherapy response in the context of a whole living organism.
Regulators proteins 14-3-3, evolutionarily conserved, bind to signalling proteins and affect their stability, activity or cellular localisation. So, they are involved in the regulation of various cellular processes, including apoptosis, the cell cycle and stress response.
In addition, the researchers found that par-5 is required for cell cycle arrest in response to replicative stress and ionizing radiation. IDIBELL-Bellvitge Biomedical Research Institute

Retinoic acid (vitamin A) and steroids are hormones found in our body that protect against oxidative stress, reduce inflammation and are involved in cellular differentiation processes. One of the characteristics of tumours is that their cells have lost the ability to differentiate; therefore these hormones have useful properties to prevent cancer. Currently, retinoic acid and steroids are being used to treat some types of leukemia.
A study led by the research group on Genes and Cancer of the Bellvitge Biomedical Research Institute (IDIBELL) has shown that loss of BRG1 gene implies a lack of response of cells to these hormones, and therefore the tumour may continue growing.
The IDIBELL research group on Genes and Cancer led by Montse Sanchez-Cespedes discovered some years ago that the BRG1 gene, a tumour suppressor, is inactivated in non-small cell lung cancer by genetic mutations. ‘The BRG1 protein is part of a chromatin remodelling complex that regulates the expression of several genes,’ said the researcher, ‘and is related to the differentiation of lung cells, allowing cells response to certain hormones and environment vitamins like vitamin A or steroids.’
When BRG1 is mutated and therefore inactive, tumour cells do not respond to the presence of these hormones and they continue growing and spreading. For this reason, these types of tumours are refractory to treatment with these substances.
‘At the moment,’ says Montse Sanchez-Cespedes, ‘we are not able to restore the functionality of a tumour suppressor gene as BRG1 in patients. Therefore, we are still far from a therapeutic application but the discovery enables us to better understand the biology of tumours. What we will try to do in the immediate future is to look for agents that specifically destroy the cells with mutated BRG1, following the strategy of lethal synthetics’.
In any case, this finding it can be useful in advancing personalised medicine, because ‘it explains why lung cancer patients are resistant to these treatments and may serve to rule out therapies with lipid-derived hormones in patients with BRG1 mutations, not just in lung cancer but also in breast and prostate, among others. ‘ IDIBELL