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Take The Challenge For Colorectal Cancer

by Colon Cancer Challenge Foundation
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Take The Challenge For Colorectal Cancer
Take The Challenge For Colorectal Cancer
Take The Challenge For Colorectal Cancer
Take The Challenge For Colorectal Cancer
Take The Challenge For Colorectal Cancer
Take The Challenge For Colorectal Cancer
Take The Challenge For Colorectal Cancer
Take The Challenge For Colorectal Cancer
Take The Challenge For Colorectal Cancer
Take The Challenge For Colorectal Cancer
Take The Challenge For Colorectal Cancer
Take The Challenge For Colorectal Cancer
Take The Challenge For Colorectal Cancer
Take The Challenge For Colorectal Cancer
Take The Challenge For Colorectal Cancer
Genome and Exome Sequencing
Genome and Exome Sequencing

PROJECT UPDATE – December 10, 2015

YOU are funding the future – the definitive future of understanding the causes of cancer including colorectal cancer among young adults. Your support funds highly focused efforts to identify genes that contribute to causing colorectal cancer and other cancers that affect both women and men.  

There you have it. It sounds dramatic and it is! Your donations make possible the complex research that will identify those most at risk of these deadly diseases and direct lifesaving screening and surveillance to those individuals.  That’s a pretty hefty explanation for the complex research your donations are supporting! But, we thought you deserved to know just how important the research your support really is.

WHAT IS SO SPECIAL ABOUT THE RESEARCH WE ARE DOING?

Early age onset colorectal cancer is a growing health concern and an important topic in international medical research centers. The incidence of colorectal cancer diagnosed in young adults has risen dramtically in the past decade.

We and others have already tested many young adult colorectal patients for all of the KNOWN genetic factors associated with colorectal cancer - FAP CRC, LYNCH, MYH, etc. Only a fraction of these young adults have a known genetic syndrome or a signficiant family history of colorectal cacner. And, the genetic factors underlying their familial predisposition have yet to be discovered.

Furthermore, recent data demonstrates that up to 75% of early age onset colroectal cancer patients have no family history of the disease - suggesting new and complex genetic factors underlie these cancers. 

It is time to step up our efforts to identify new genetic causes for CRC.

WHAT’S SPECIAL ABOUT THE TECHNOLOGY YOU’RE FUNDING?

With your help we are performing whole exome and whole genome sequencing. This is a new technology that massively expands the amount of DNA that can be tested and investigated.  We now have the technological capacity to sequence the entire genome. The exomes are the portions of a gene or genome that code information for protein synthesis – otherwise known as CDA.

In addition we are able to also sequence so called non-coding regions that have not previously been explored for factors that have important functional effects and also contribute to CRC risk.  

BUT WHAT IS TAKING SO LONG?

First, identifying a group of persons sharing a particular statistical or demographic characteristic isn't easy.

And second, the technology is so new it’s breaking the technological barriers of all previous genetic research. The information is overwhelming – we’re talking 100s of 1000s of genetic variants. Our bioinformatics are racing to keep pace with the technology and to manage all of the information it is supplying.

Finally, although costs have decreased significantly, it is still very expensive.

WHAT’S THE POTENTIAL IMPACT?

These techniques are the best way of identifying variations in DNA sequences and the future of genetic research of diseases going forward. This is the future for identifying novel genetic elements that contribute to complex human diseases including colorectal cancer.

We have the potential for discovering novel therapeutic targets and genetic biomarkers that will be useful for drug discovery, patient selection and stratification in complex human diseases including colorectal cancer.

Simply put, with your support we have the ability to save lives.  

We can't thank you enough for your continued support of this lifesaving work. 

THE COLON CANCER CHALLENGE FOUNDATION 

YOU - Are Funding The Future!
YOU - Are Funding The Future!

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McNamaraKateMeet&Greet
McNamaraKateMeet&Greet

PROJECT UPDATE: 

June 4, 2015

‘The Answer is in DNA’

We recently caught up with CCCF Research Fellow Kate McNamara and asked her to tell us why her work is important, worth the effort and worth your very generous support.  This is what she had to say.

“What I think about is a billboard hanging outside of Princess Margaret Cancer Centre that reads … 'The answer is in DNA'. You see … even cancers related to environmental exposures develop in the context of genetic susceptibility and genetic events. The science of analyzing the human genome is rapidly evolving and is allowing us to better understand cancer development and how to effectively screen and treat so as to save lives. Toronto and other elite cancer centers are pioneering this science but this is possible only with funding support and the efforts of clinicians, scientists, support staff, investors, and all persons contributing to the cause in any way.”

We couldn’t agree more and with your help we can fund Kate’s work for another successful year. To learn more about Kate and the incredible team at the Zane Cohen Centre for Digestive Diseases (ZCC) take a look at their spring newsletter. http://bit.ly/1KOVai6 

Many of you were able to meet Kate personally at our Inaugural Early Age Onset –Colorectal Cancer (EAO-CRC) Summit held at Memorial Sloan Kettering Center this past March.  Kate gave the audience a glimpse into the world of Whole Genome Sequencing and her efforts to define novel genetic elements contributing to the incidence of EAO CRC.  For those of you who missed the Summit the video and slides are available on our website http://coloncancerchallenge.org/about-us/eao-crc-summit

Updates from Toronto:

Unfortunately, the initial attempt at exome sequencing in the early-onset cases was not successful. The sequencing data was very poor quality and so the process had to be repeated including library preparation, sequencing, and initial pipelines analysis. Such is research... The second attempt at germline DNA sequencing is complete and initial QC looks good. Preliminary data analysis should be complete by the end of next week.

In the interim, an interesting trio presented in clinic -- 13yo with CRC and consanguinous parents (first-degree cousins once removed). Separate exome sequencing was performed and we have done some preliminary analysis to search for rare variants that fit a recessive model of inheritance. There are a few candidate genes. We will evaluate these genes in the set of early-onset cases as soon as that data is available and will look in other Toronto CRC datasets. Much time is spent trying to research/learn bioinformatics tools available to interrogate sequencing data.

At the end of the month Kate will be traveling to the annual meeting of the American Society of Colon and Rectal Surgeons (ASCRS) in Boston, MA where she will give a poster presentation: 'Is there a role for prophylactic colectomy in Lynch syndrome patients with inflammatory bowel disease?'

In her presentation Kate presents a small case series of these unique patients, assess CRC incidence, and posit whether risk for CRC development is sufficiently increased in the setting of two important risk factors to warrant prophylactic colectomy. The case series is the largest reported to date. By traveling to the conference Kate has an exciting opportunity to present her findings and hear from leaders in this specialty area.  Kate has also written this into manuscript form and it is pending submission to Diseases of the Colon and Rectum (the journal of ASCRS).

Stay tuned for regular updates on Kate’s work, progress and of course any breakthroughs.  For more information on our work focused on early age onset of colorectal cancer visit our website http://coloncancerchallenge.org 

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Dnasecquencing
Dnasecquencing

Why would we use your money to send our research fellow Dr. Kate McNamara to Toronto to sit on a lab bench in a cubicle for hours/days on end you ask? 

Good question with a few very important answers!  

First and foremost the Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital in Toronto is home to Dr. Steven Gallinger and his lab is at the forefront in the field of GI cancer genetics, both in Canada and internationally. Working with Dr. Gallinger's team affords Kate the opportunity to utilize the facility's advanced sequencing capabilities and the team’s expertise to analyze the data.  She also has access to one of the most extensive and organized datasets of hereditary and early onset CRC cases in the world.  Very few institutions would offer the samples that Kate has been able to compile using the Familiial Gastrointestinal Cancer Registry (FGICR).

Secondly our theory is that germline and tumor DNA sequencing of early-onset colorectal cancer EOCRC cases will identify novel genes and/or gene pathways involved in the carcinogenesis or literally the 'creation' of EOCRC. Many early onset CRC cases are associated with hereditary cancer syndromes ie. Lynch syndrome that are under-diagnosed.  Being able to identify those families and young adults with the greatest risk of developing colon or rectal cancer is imperative to halt and reverse the numbers of those diagnosed with the disease.  It would also allow us to improve the management and care of young adults already diagnosed with the disease and increase the number of families receiving genetic testing and cancer screening as needed.  

Finally, family registries have been demonstrated to improve management of patients with hereditary cancer syndromes. Unfortunately, the US is lacking in well-organized registries. The FGICR is a valuable model for an effective registry. Familiarizing ourselves with how the registry operates and bringing this knowledge to US colleagues can hopefully encourage organization of databases/registries here at home.

You have an opportunity to learn more about this V.I.P. Very Important Project firsthand in just a few short weeks at the nation’s first Summit focused on Early Age Onset of Colorectal Cancer.  Thanks to you and your generous support we are organizing and co-hosting the groundbreaking event on March 21st.  We are bringing together the nation’s experts on EAO-CRC and young patients to address one of the nation’s emerging public health crises and set the national agenda to tackle the issue head on. Our research fellow Dr. Kate McNamara will give a report on her progress.  

To register please visit our website – http://events.coloncancerchallenge.org

We can't thank you enough for your support of our mission of World Without Colorectal Cancer. I hope to see you at the Summit. 

Thomas K. Weber

President & Founder

Colon Cancer Challenge Foundation 

 

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McNamaraandHaroldsdottirCGA2014
McNamaraandHaroldsdottirCGA2014

Not everyone feels the same way but, if we told you that one of the goals of our research is to identify those at risk of developing late stage colon or rectal cancer at a very early age we think you would agree.  We are dedicated to preventing colorectal cancer at any age but especially concerned about those diagnosed with late stage colorectal cancer (CRC) between the ages of 20-40. 

And, our research fellow Kate McNamara certainly agrees.  Kate has already spent long days and nights reviewing thousands of colorectal cancer cases in one of the world's most comprehensive familial gastrointestinal cancer registries.

Kate's first assignment was to select appropriate cases for further study.  Then she focused on preparing tumor and germ line DNA samples for genomic sequencing. New genomic technology offers researchers like Kate the opportunity to study the biology of colorectal cancer tumors and uncover variations that predispose individuals to greater risk.  The outcome of this research will also deliver the knowledge necessary to develop targeted treatments to more effectively treat patients and monitor them for recurrence.  The sequencing of these samples can take months.  In the meantime Kate keeps herself busy helping out on a few other worthwhile projects.  

For example, she is also working on a project focused on identifying patients at high risk for recurrence while undergoing curative resection for colorectal liver metastases.  The ability to identify patients might lead to better selection of patients for surgery and for neo- and adjuvant chemotherapy and better outcomes.  

And finally, in her spare time Kate is assisting a team investigating the molecular features of missed and detected cancers at colonoscopy. In brief, colonoscopy is the gold standard for detecting colorectal cancer and its precursors. However, 2-6% of colorectal cancer cases present within 3 years of a negative colonoscopy.  These are the so-called 'new or missed cancers'.   It is important to analyze the molecular features of these ‘new or missed cancers’ to determine whether there are differences in carcinogenesis of missed and detected CRC.

We will be bringing you regular updates on Kate’s work, progress and of course any breakthroughs.  For more information on our work focused on early age onset of colorectal cancer visit our website http://coloncancerchallenge.org

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Organization Information

Colon Cancer Challenge Foundation

Location: White Plains, NY - USA
Website:
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Twitter: @CCCFDN
Colon Cancer Challenge Foundation
Catherine Montaldo
Project Leader:
Catherine Montaldo
White Plains, NY United States

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