Kristah Halton

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Posts by Kristah Halton

Never Too Young- Laura’s Story –

Never Too Young- Laura’s Story –

Thinking back to her week-long stay in the hospital, one memory stands out to Laura Jambrovic amidst the endless tests, beeping of machines, sleepless nights and morphine-dulled pain—her toenails, painted pink.

She had had them done for her graduation from McMaster University just two weeks prior. Now, they were peeking out from the too-short blanket on her gurney as the hospital orderly wheeled her through the halls for yet another test, singing gently to her in Italian.
Before being admitted to the hospital early in the morning on Friday, June 24, 2016, after spending the night vomiting and in severe abdominal distress, Laura had spent most of the previous year dealing with debilitating cramping, bloating, irregular bowel movements and numerous fruitless visits to doctors.
A weekend of tests revealed the source of Laura’s pain—a tumour in the lower colon so large that her doctors called it a “complete obstruction.” Surgeons removed a thirty-centimetre portion of her colon and performed an emergency colostomy—a procedure that brings one end of the colon through an opening in the abdominal wall, where a bag is attached to collect stool. The tumour and a cluster of the surrounding lymph nodes were sent for testing.

Ten days later the results came back.
Colon cancer.
Stage III.

As her older brother, it’s the initial phone call from our dad that I remember most.
“I’m at the hospital with your sister.”

I had to attend a wedding that weekend and the doctors didn’t know what was wrong with Laura yet so Dad told me not to worry.
“Try and have fun,” he said. “I’ll keep you posted.”

I knew she had been dealing with a lot of discomfort for the past year and part of me was happy that at least now she might finally get some answers.

Laura and I have always been close despite our age difference. She is three years younger than I am, but we’ve always looked and acted so similarly people have often assumed us to be twins.
As the older sibling, I was always giving Laura guidance and advice, but for the first time in my life I couldn’t tell her I knew what she was feeling, I couldn’t say: “Don’t worry, I’ve been there and it will get better.”

All I could think was: “Why couldn’t it be me?”

During her treatment and recovery, Laura and I spoke at length about her illness.

“In hindsight, there were signs I had problems stretching back before high school,” she told me. For years, she took Metamucil to combat irregular bowel movements, and she struggled with constipation and cramping throughout the years, but she always attributed it to diet.
By June, 2015, her symptoms worsened - cramping became severe and she had blood in her stool. At times, the pain grew so bad, she didn’t want to get out of bed. Multiple blood and stool sample tests revealed nothing conclusive, but doctors suspected irritable bowel syndrome (IBS).
A health and fitness buff, Laura became even more conscious of her diet, keeping a food diary to try and find a pattern between what she ate and her symptoms, but no pattern emerged and she began to despair.

At one point, feeling “trapped and hopeless,” after leaving another unsuccessful doctor’s appointment, Laura broke down. While waiting for the bus she needed to take her home, she spied a nearby dumpster and hid behind it so no one would see her cry.

Cancer was never even mentioned until her trip to the emergency room.

The technical name for Laura’s diagnosis is low grade colonic adenocarcinoma in the sigmoid colon. The colon, also known as the large intestine or bowel, is a muscular tube measuring about 1.5 metres long that dehydrates the leftover remains passed along by the stomach and small intestine, turning it into stool.
Sometimes the cells lining the colon or rectum become abnormal, forming non-cancerous tumours or growths called polyps. Not all polyps turn into colorectal cancer, but colorectal cancer almost always develops from a polyp. When a cancerous polyp gets large enough, cancer cells can then grow into the organ wall, gaining access to blood and lymph vessels, enabling it to spread.
The days following Laura’s trip to the emergency room in June 2016 were an emotional whirlwind. My drive home was a blur of barely-contained panic, but the twin, haunted looks my parents gave me when I walked in the front door will be with me until the day I die.

As the days passed, crushing fear, sadness and pain gave way only to frustration, anger, guilt and self-pity. We agonized over the events of the previous years—could we have done more? How could this have happened? How does a seemingly healthy 22-year-old get a disease like this? And perhaps most important: Why wasn’t it caught earlier?

Cases like Laura’s are so unusual that her surgeon told her she is the youngest colorectal cancer patient he had ever operated on.
However; a recent Canadian study, Trends in colorectal cancer incidence and related lifestyle risk factors in 15–49-year-olds in Canada, 1969–2010, shows that while overall colorectal cancer incidence rates in Canada have declined slightly since the mid-90s, incidence rates in those aged 15–49 have actually increased, especially in the 15–29 age group, “in whom the incidence rate increased 6.7% per year between 1997 and 2010.”

Dr. Prithwish De, co-author of the study and the Director of Surveillance and Cancer Registry at Cancer Care Ontario, said the increased rates of young-onset colorectal cancer were “surprising” because it is typically thought of as being an older person’s disease. He calls the study’s results “alarming.”

Ultimately, testing revealed that Laura does not have any known genetic markers associated with young-onset colorectal cancer, but about 30% of young-onset cases develop in those with a family history of the disease or genetic disposition, and both the U.S. Preventative Services Task Force and the Canadian Task Force on Preventive Health Care recommend regular screening beginning at the age of 40 for these high-risk individuals.

For Canadians at an average risk, screening is recommended for people aged 50 to 74. Despite rising young-onset incidence rates, screening is not recommended for average-risk individuals under 50.

Diagnosis is tricky in young people like Laura, because of the similarity of colorectal cancer symptoms to other, less serious, gastrointestinal problems like IBS, or an iflammatory bowel diseaese (IBD), such as Crohn’s or ulcerative colitis. Further complicating diagnosis, Canada also has one of the highest rates of IBS, with five million-predominately female-Canadians currently suffering.

Dr. De believes that a team effort is required to combat delayed diagnosis.

“The healthcare community definitely needs to be more aware of the rise in colorectal cancers in young people,” Dr. De said. And “symptoms need to be communicated more clearly,” but there also needs to be greater vigilance among young people.

In the weeks immediately following her June 2016 surgery, Laura did her best to keep her spirits up. Her physical and mental wounds were still raw, however, and the reading she did on treatment side-effects and long-term survival rates were depressing. The week-long stay in the hospital was hard on her body, causing her to drop from a muscular 142lbs to a too-lean 130lbs. The incisions in her abdomen were tender and she had no energy, often growing light-headed and occasionally fainting.

The colostomy bag was inconvenient and made her feel unattractive, but what really weighed on her, especially at first, was the idea that she might never be able to push herself in the gym like she used to. For her, the gym is a sanctuary where she can clear her head, and especially in the initial few weeks of post-op shock, thoughts that that had been taken from her were especially crushing.

“I hid my gym stuff. It [was] just so hard to look at,” she told me when we sat down that summer to formally discuss her illness. “The hardest part to come to terms with was not being able to do things I love.”

The year following Laura’s diagnosis has been a roller coaster. After the initial panicked days and weeks, I buried myself in research, hoping that an understanding of why and how this had happened would be cathartic.

Meanwhile, Laura began her treatments. Prior to chemotherapy, she underwent oocyte cryopreservation—the process of freezing and storing her eggs—to guard against any potential fertility issues caused by treatment.

Fears that treatment would be unsuccessful-or that it would be successful, but with terrible side-effects-kept her awake at night. More than once she caught herself staring at her long, blonde-streaked hair, anxious that she might lose it.

The worst part for me was knowing that she was going to have to deal with these side effects without knowing until treatment was finished whether it worked or not.
But Laura was determined to regain a degree of control. Within a few months of beginning her twice-monthly chemotherapy treatments, she returned to the gym despite frequent bone-deep weariness. When her hair started falling out she cut it short and was able to donate it to other cancer patients. She even joined a dog-fostering group.

Slowly, a feeling of normalcy began to return.

Before I knew it, it was February 2017, and Laura had her final dose of chemotherapy. We waited, breath held, for the results of her follow-up colonoscopy. And then we got the results.
No sign of disease. Her colon, at least, was clear.

The vice grip on my heart I had forgotten was there, released, and I felt like I could finally begin to relax again. A few weeks later, she adopted a puppy, fulfilling a lifelong dream, and towards the end of April she had surgery to reverse her colostomy. When I visited her at the hospital, she had a big grin on her face. The mood could not have been more different from her initial visit. Laura kept feeling at her side, not quite believing that she was whole once again.

“I can’t believe it’s finally gone,” she said. “It feels so weird.”

It wasn’t all good news - a follow-up CT scan done around the same time as the colonoscopy revealed a couple of small spots on her liver and a lung that doctors wanted to keep an eye on. We were nervous, of course, but after all the worry and frustration of the previous year, this felt minor. Laura returned to her part-time job and began planning a trip with a friend, pending the results of her next follow-up appointment.

On July 20, 2017, she was given the all-clear from her surgeon. The spot on her liver is nothing to worry about, and though they are going to keep an eye on her lung, there was no reason she should not go on her trip. Just three weeks later, she was on a plane to Amsterdam.

When I woke up one morning to a series of frantic Facebook messages from Laura detailing her misadventures with the German train system, I couldn’t help it - I laughed. A similar awakening prior to her diagnosis would have given me fits, but now it feels so good to be able to give her advice from my own experiences again.

“Don’t worry, Laura. I’ve been there and it will get better.”

David J, Laura’s brother

“I promised myself that if I survived I would live—really live. I regretted letting fear hold me back, and vowed to give life everything I had if I made it out of this journey alive. I have since applied to nursing programs and am anxiously/ eagerly awaiting a reply. It is my hope to one day work as a paediatric ostomy care nurse. I have also gone backpacking across Europe, and plan to visit Southeast Asia next year. I never would have done these things had I not had cancer – for that I am incredibly thankful. Cancer did not teach me to be fearless, but to go on despite fear. ”

Laura J.

This March Give Back!

Men and women have been adorning themselves with jewelry for ages.

There are many reasons why people love their bling:

#1 As accessories used to spruce up any outfit
#2 As emotional pieces tied to heirlooms or sentimental gifts of love and affection
#3 Or as symbols of social status

Whatever your reason, ANZIE jewelry has stunning pieces that will not only turn heads but also help save butts!

During March, Anzie Jewelry will be donating 10% of their proceeds (20% if the item is in the “Lifesaver” collection) to Colorectal Cancer Canada!

For more information: https://www.anzie.com/product_life.php

Our Story: the Halladays

Wouldn’t it be nice if “our story” was just one about our marriage, our children, our life together and our family .. but “our story” also involves cancer. Colorectal cancer that my husband has been fighting for 3 years.

Ryan was diagnosed with stage 3 colorectal cancer in March 2015. He was 39 years old, and otherwise in great health. In September 2015, he had treatment to shrink and surgically remove the tumor. He also received chemotherapy to ensure the cancer was gone. In January 2017, through a routine scan, it was discovered that the cancer had moved to his liver. In February 2017, he had 1/3 of his liver removed. In June 2017, he had a clean CT scan, but in November through a visit to the ER department, a CT scan showed a recurrent mass (cancer) on the outside of this rectum. This is called a “local re-occurrence”.

Our family, our amazing supportive family, has done this a few times: receive the news, process it, and then get ready for the “fight of our lives”. This one was the hardest: we know that when cancer comes back, it’s never good. We waited 10 days, 10 really long and sad days to meet with the surgeon, who sat across from us and said there was “nothing” that they could do, and a referral would be put in to someone who might be able to help.

This was devastating and horrible! I wouldn’t wish this moment on anyone. The next day my husband and I woke up, looked at each other and decided “this can not be it”. We are not done fighting, there has to be an option, there must be someone out there who can help us.

I have worked in not-for-profit my whole career, yet I never thought to find the association that deals with colorectal cancer, not until that day. I wish that I had found them 3 years ago because that moment, that day when I reached out to Colorectal Cancer Canada, our life changed, our fight changed, and our outcome changed.

A representative from Colorectal Cancer Canada reached out to me on a Saturday night, immediately I emailed her and talked to me for 40 minutes about options. She gave me hope for the future, and within seconds I knew I had an advocate. We were referred to the Odette Cancer Centre at Sunnybrook, a centre of excellence. We were also told about the “Young Adult Colorectal Cancer Clinic” headed up by Dr. Shady Ashamalla. This is a clinic which specializes in treatment for those people diagnosed with the disease before the age of 50. We had an appointment with a highly skilled and expert surgeon in a week’s time. He believes he can remove the tumor and bring my husband back to health, a life without cancer. A week later, we had met the rest of the team: the radiation oncologist and medical oncologist. Each appointment, moved us further in our plan and each interaction with the staff at Sunnybrook and Colorectal Cancer Canada has been positive, uplifting and safe.

As I mentioned before, that first call I made to Colorectal Cancer Canada changed our life because we took the power back, we have a plan and an excellent care team. It changed our fight; now we are fighting with more knowledge; our team of supporters has grown; we have an entire organization and cancer clinic supporting us in this journey and it has changed our outcome. Before I called Colorectal Cancer Canada, we had to sit down and tell our young daughters for the 3rd time that their dad has cancer and unsure if anything could be done. After the call and the support we received from Colorectal Cancer Canada though, we were able to tell our daughters differently! Yes, their dad has recurrent cancer, but his medical team has a curative treatment plan in place and is working very hard to achieve a goal of no evidence of disease (NED) for him. We know nothing is absolute, and anything can happen, but we have hope, knowledge and advocates as we navigate through this part of the journey with Colorectal Cancer Canada, and that is a huge difference!

Our story if one of hope. Cancer will not define us! Instead, our determination and willingness to do everything we possibly can to help my husband Ryan will define us as a united family. Thank you Colorectal Cancer Canada!

With much gratitude,
Christina Halladay

Starlette promotes bralette for a good cause – Order yours by March 13, 2018

Starlette promotes bralette for a good cause – Order yours by March 13, 2018

Montreal actress Juliette Gosselin partners up with Sokoloff Lingerie to help increase awareness of colorectal cancer among women. She named her bralette Jacqueline in honor of her grandmother, who fought this disease. All the sales profits will be donated to Colorectal Cancer Canada.

The Colorectal Cancer Canada is dedicated to increasing awareness of colorectal cancer, supporting patients, and advocating for population-based screening and timely access to effective treatments. Worldwide, colorectal cancer is the third most common cancer afflicting humans.

This collab falls under a bigger initiative called B-Cause where other Montreal artists, joined Sokoloff Lingerie to create bralettes for different charities.

BRALETTES FEATURES
Loungewear satin bralette
Very deep cleavage
Large frilled elastic at underbust
Delicate bow at center front
Non-adjustable straps
Hook & Eye back closure
Perfect for indoor cooconing
Made in our very own Montreal workshop

MATERIAL
100% polyester.

SIZES
We recommend a SMALL for cups:
32A / 34A / 36A / 32B / 34B / 32C
We recommenda MEDIUM for cups:
36B / 34C / 36C / 32D
We recommend a LARGE for cups:
34D / 36D
If needed, refer to our fitting room tips to find your size !

**PRE-ORDER ONLY UNTIL MARCH 13TH. BRALETTES WILL BE SHIPPED ON THE LAST WEEK OF MARCH*

To learn more about Juliette Gosselin click here!
To learn more about Colorectal Cancer Canada, click here!

Dress in Blue Day

Dress in Blue Day

Today is DRESS IN BLUE DAY! Together, let’s show our support to those affected by colorectal cancer. Share your photos using #DressinBlueDay #ColorectalCancerAwarenessMonth

On Dress in Blue Day, and throughout Colorectal Cancer Awareness Month, you can help raise awareness about the second most common cancer in Canada. Today, and all throughout the month, we encourage families, businesses and organizations to dress in blue to show support for those touched by colorectal cancer, and to also share important information on how a healthy lifestyle and effective screening can save lives.

Why Go Blue?

Dress in Blue Day is a good opportunity to engage in an activity that raises awareness about colorectal cancer prevention, while celebrating survivors and remembering loved ones lost too soon. In addition, organizing a fundraiser in your community forges stronger bonds between friends and neighbors while supporting the Colorectal Cancer Canada mission. We are the country’s leading colorectal cancer not for profit patient organization dedicated to colorectal cancer awareness and education, supporting patients and their families and advocating on their behalf.

How to Go Blue?

• Ask friends and families to show their support by wearing blue
• Hold a contest for the most creative blue outfits
• Distribute colorectal cancer awareness materials
• Decorate your home or workplace with blue lights and blue accents
• Share on social media why this cause matters to you

5 steps to raise money for the cause
1. Visit dressinblueday.ca
2. Create a team
3. Set a goal
4. Start fundraising
5. Wear blue

For more information, visit dressinblueday.ca or contact Frank Pitman at frankp@colorectalcancercanada.com (514) 875-7745 ext. 2529

The Christodoulou Story

The Christodoulou Story

My name is Franca Christodoulou and this is my story. At age 49 my husband Chris was diagnosed with Stage 4 Colon Cancer that had metastasized to his liver. As you can image, this came as a complete shock and changed our world forever. Our focus was to do anything possible to provide my husband the best treatment options so that he would be around for our precious family, as we have 3 young children; but we felt lost, confused and helpless as we did not know where to turn to for guidance.

I was made aware of Colorectal Cancer Canada from a doctor I was accidently referred to and it changed our lives. I decided to call the number and spoke with Frank, a wonderful gentleman from Montreal, who told me “you’ve called the right place” and that he would have someone from the Toronto office call me. I received a call right away from Filomena and as soon as I spoke with her I indeed knew that I had called “the right place”. She was passionate, caring and a wealth of knowledge. She encouraged us to attend monthly colorectal cancer information and support group meetings. We started to attend these meetings and they have provided us with a wealth of information, support and friendship. Filomena reviewed my husband’s case and made us aware of new options available to us. She was influential in connecting us to the right doctors and my husband underwent surgery at Sunnybrook in August 2017 to insert a Hepatic Arterial Infusion pump for the treatment of his disease. Colorectal Cancer Canada was instrumental in helping to make this treatment available in Canada through a clinical study at Sunnybrook Health Sciences Centre. We feel truly blessed to have Filomena and Colorectal Cancer Canada take on the fight to provide patients with the best treatment options available and their tireless efforts to bring new treatment options to patients who might not otherwise have access. Colorectal Cancer Canada provides guidance to all members who attend these monthly meetings and go above and beyond to help support all of us regardless of disease stage or where they are in their journey. I strongly recommend any patient who is diagnosed with colorectal cancer contact Colorectal Cancer Canada. It could change your life.

With all our love and appreciation.
The Christodoulou Family

CCC TESTIMONIAL – Gemma Madamba

CCC TESTIMONIAL – Gemma Madamba

“My name is Gemma (Filipino-Canadian). I have colorectal cancer, stage 3b with no symptoms before I got diagnosed. I am 55-year-old, single mom with three sons and one grandson and I am the first cancer patient in my family. Every cancer patient differs in terms of struggles because each of us have a different system where our body responds differently from the chemo drug and other drugs to make us well. I had suffered side effects that my oncologist calls rare, but I battle my disease with faith in God, faith in my doctors, medical team and faith in myself that I have lived to this day to share my story.

I firmly believe that fighting cancer with positivity is the most powerful weapon to battle it. I was inspired and dedicated to volunteer as a fundraiser for Colon Cancer Canada now Colorectal Cancer Canada and I support the Wendy Bear Assistance Program which assist colorectal cancer patients with their financial needs. A legacy that I wish to be a part of Wendy Sittler’s goal to help those afflicted with this disease. I call my campaign “Gemma Loves Blue”.

https://ccc.akaraisin.com/personalpages/07bd5aec6a4d49aebe3f7ae79940da97

To date I was blessed to raise $3,445.00 and it will continue to rise, as I find more people to support our cause. I believe in the importance of this program and I wanted to do more to help my fellow colorectal cancer patients. It has been a year that I am now a volunteer in spreading awareness and motivating a lot of people to support the Wendy Bears. The most uplifting part is I had the opportunity to reach out to colorectal cancer patients and we bonded in friendships in terms of comforting each other’s pains and suffering because of this disease. I believe that I am a living legacy to inspire others with the disease.

I am determined in what I do, and I am encouraging my fellow colorectal cancer patients to be strong and if you can join me supporting the cause of Colorectal Cancer Canada then we can make a difference not only to ourselves but for others as well. What is wrong with our BUTT can make wonders for others if we try to be a part of every BUTT around us.”

Canadian’s New Food Guide Moving Away From Meat Consumption – Give it a try with us during Meat Free Week!

Canadian’s New Food Guide Moving Away From Meat Consumption – Give it a try with us during Meat Free Week!

In the past two decades, Canadians have shifted towards a diet which includes more fruits and vegetables, cereal products, and nuts and beans.

With more and more Canadians making the switch, it is no wonder that Health Canada just released its preliminary draft of Canada’s new Food Guide, the first such overhaul of the country’s nutrition policy in ten years. The changes are long overdue, say health care experts, many of whom see the proposal as a step in the right direction.

The preliminary draft highlights include:

• The importance of adding whole foods to your diet, specifically plant-based foods (such as legumes) as a preferred source of protein
• Regular intake of vegetables, fruit, whole grains and protein-rich foods, especially plant-based sources of protein
• A shift away from animal foods by advising that people eat foods with unsaturated fat instead of saturated fat

Even though statistics in the last 3 decades show a steady decline in Canadian meat consumption, there are still many meat lovers that remain skeptical about making the switch despite the World Health Organization’s classification of red meat – including, beef, veal, pork, lamb, mutton, horse, and goat – as “probably carcinogenic to humans”.
WHO found an even stronger link between processed meat – such as salami and hotdogs, and bowel cancer.

Studies conducted by the World Cancer Research Fund show bowel cancer risk increases by 17% per 100g of red meat consumed per day and that bowel cancer risk increases by 18% per 50g of processed meat consumed per day.

• ¼ cooked hamburger = 80g
• 8 oz steak = 170g
• Spaghetti Bolognese sauce = 100g
• 1 large sausage = 40g processed meat
• 3 slices of ham = 70g processed meat

Read more about how you can reduce your bowel cancer risk.

Try Going Meatless For a Week With Us!

People around the world will be going meatless next week including all of us at Colorectal Cancer Canada for Meat Free Week (18th-24th September 2017). This new campaign challenges participants to give up meat for seven days and raise funds for a great cause.

Going meat free for one week creates a great opportunity to start thinking about how much meat you eat and the impact eating too much meat can have.

Everyone is invited to take the Meat Free Week challenge and discover how easy it is to make little changes that can create a big difference. Challenge yourself, your family, your friends and colleagues to give up meat for seven days.

Sign up for Meat Free Week and raise funds for a great cause!

Not able to participate, but still want to help make real change happen? Make a donation today.

If you’re already living meat free, there are still plenty of ways you can get involved in Meat Free Week.

+ Meat Free Week: Live well. Eat well. Be well.

• Adopt a physically active lifestyle.
• Consume a healthy diet with an emphasis on plant-based foods.
• Maintain a healthy body weight.

Are you following our healthy our foods that fight cancer program?
Once you’ve made it through Meat Free Week, this is a great on-going support program that can help you eat better and live healthier.

Check us out today via our website or facebook page!

About Foods That Fight Cancer

Who Are We?

We are believers of FOOD.

We want to empower Canadians to take charge & take over their health!

So Welcome fellow food enthusiast! Learn about foods here, find your favorites recipes, invite your friends & family, and TAKE OVER your kitchen & your health!

References:

http://www.statcan.gc.ca/pub/21-020-x/2009001/part-partie1-eng.htm
https://www.cantechletter.com/2017/07/look-meat-eaters-canadas-new-food-guide-will-turn-vegetarian/

Using Epigenetics as Biomarkers for Colorectal Cancer

Using Epigenetics as Biomarkers for Colorectal Cancer

By Marc Aurèle Chay

http://www.genengnews.com/gen-news-highlights/pan-cancer-epigenetic-signature-readable-in-circulating-tumor-dna/81252334

http://www.genengnews.com/gen-news-highlights/pan-cancer-epigenetic-signature-readable-in-circulating-tumor-dna/81252334

In Canada, screening for colorectal cancer can be done using the FOBT or FIT tests. These currently have suboptimal diagnostic accuracy, which is why researchers are investigating other avenues for non-invasive detection of early CRC. Scientists have found that in many early-stage cancers, including CRC, epigenetic alterations are present in much higher frequency than genetic mutations. As such, DNA methylation, ncRNAs, histone modifications are being investigated for potential diagnostic and prognostic markers of CRC.

DNA Methylation Biomarkers

Blood, stool, saliva and urine are being examined by the research community for these markers. DNA methylation in particular is being studied extensively, and some groups have reported sensitivities of 90-95% with specificity ranges of 85-94% for certain biomarkers in CRC. Some genes have risen to be the most promising markers, including the tumor specific M2 isoform of pyruvate kinase (PKM2), tissue inhibitor of matrix metalloproteinase 1 (TIMP1), vimentin (VIM) and septin 9 (SEPT9). DNA methylation is also being investigated for prognostic biomarkers and predictive markers for response to treatment. In particular, CpG island methylator phenotype (CIMP) positive cancers are found to correlate strongly with overall unfavorable prognosis, but seem to benefit from 5-FU based adjuvant chemotherapy. Hypermethylated Transcription Factor AP-2 Epsilon (TFAP2E) seems to also predict response to 5-FU based chemotherapy.

Histone Modification Biomarkers

Diagnostic and prognostic biomarkers using histone modifications have been much less studied, partly due to technical limitations of assays that are used to characterize the chromatin landscape. Some studies show acetylation of H3 lysine 56 and di- or tri-methylation of H3 lysine 9 and 27 have potential to be prognostic markers in CRC. These results are still currently preliminary and are expected to be further explored with the new bioinformatic tools and next-generation sequencing technologies that are being optimized.

Non-Coding RNA Biomarkers

On the other hand, non-coding RNAs, and in particular miRNAs, have triggered a substantial interest from the scientific community. Blood and stool based biomarkers have been investigated, and multiple candidates such as miR-21, miR-92a, miR17-3p or miR-106a have come up as potential diagnostic markers. MiR-21 has also been associated with poor patient survival, and several other miRNAs have been proposed as prognostic markers. As research evolves, scientists hope to engineer a panel of biomarkers that will be able to accurately identify and predict prognosis for early stage CRCs.

Epigenetics has offered us new tools to understand the complex etiology of colorectal cancer. As the scientific community further elucidates the mechanisms at play, epigenetic biomarkers to diagnose, classify and predict prognosis of CRC are also uncovered. Further research on these biomarkers may provide us with high performance assays that can be used to prevent and better manage patients with CRC.

References

Mitchell, S.M., Ho, T., Brown, G.S., Baker, R.T., Thomas, M.L., McEvoy, A., Xu, Z.-Z., Ross, J.P., Lockett, T.J., Young, G.P., LaPointe, L.C., Pedersen, S.K., Molloy, P.L., 2016. Evaluation of Methylation Biomarkers for Detection of Circulating Tumor DNA and Application to Colorectal Cancer. Genes (Basel) 7. doi:10.3390/genes7120125

Okugawa, Y., Grady, W.M., Goel, A., 2015. Epigenetic Alterations in Colorectal Cancer: Emerging Biomarkers. Gastroenterology 149, 1204–1225.e12. doi:10.1053/j.gastro.2015.07.011

Rozalski, R., Gackowski, D., Siomek-Gorecka, A., Banaszkiewicz, Z., Olinski, R., 2016. Urinary Measurement of Epigenetic DNA Modifications: A Non-Invasive Assessment of the Whole-Body Epigenetic Status in Healthy Subjects and Colorectal Cancer Patients. ChemistryOpen 5, 550–553. doi:10.1002/open.201600103

Sameer, A.S., Nissar, S., 2016. Epigenetics in diagnosis of colorectal cancer. Mol Biol Res Commun 5, 49–57.

Sazanov, A.A., Kiselyova, E.V., Zakharenko, A.A., Romanov, M.N., Zaraysky, M.I., 2016. Plasma and saliva miR-21 expression in colorectal cancer patients. J. Appl. Genet. doi:10.1007/s13353-016-0379-9

Understanding What Epigenetic Means in Colorectal Cancer

Understanding What Epigenetic Means in Colorectal Cancer

By Marc Aurèle Chay

Vaiopoulos, A.G., Athanasoula, K.C., Papavassiliou, A.G., 2014. Epigenetic modifications in colorectal cancer: Molecular insights and therapeutic challenges. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1842, 971–980. doi:10.1016/j.bbadis.2014.02.006

Vaiopoulos, A.G., Athanasoula, K.C., Papavassiliou, A.G., 2014. Epigenetic modifications in colorectal cancer: Molecular insights and therapeutic challenges. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease 1842, 971–980. doi:10.1016/j.bbadis.2014.02.006

Consider the genome as words in a book, and epigenetics as the punctuation and accents that dictate the way each sentence is read. Epigenetic regulation refers to the heritable and reversible mechanisms that alter gene expression without affecting the underlying DNA sequence. Epigenetic mechanisms, among others, include DNA methylation, non-coding RNAs, chromatin remodelers and histone post-translational modifications. They play a crucial role in the proper functioning of a cell. In cancer, genetic and epigenetic alterations are linked together and can both contribute to the activation of oncogenes and/or the silencing of tumor suppressors. In colorectal cancer (CRC), understanding the epigenetic mechanisms driving pathogenesis have been a focus of the scientific community since the early 2000s. Many potential driver aberrations have been found, but as with genetic mutations, there isn’t a single mechanism that can explain CRC development.

DNA Methylation in CRC

DNA methylation refers to the addition of a methyl group to a nucleotide, usually a cytosine in a CG context. When present at CpG islands, it correlates strongly with repression of the nearest gene. Researchers have found global genomic hypomethylation, especially in CIN CRCs, as well as hypermethylation in promoter regions of specific genes such as APC, Cadherin-1 (CDH1), runt-related transcription factor 3 (RUNX3), mutL homolog 1 (MLH1), O-6-methylguanine-DNA methyltransferase (MGMT), cyclin-dependent kinase inhibitor 2A (CDKN2A), and RASSF1A.

Histone Modifications in CRC

Other than DNA methylation are histone post-translational modifications. These are the addition of methyl/acetyl/ubiquityl/phosphate groups to the proteins that make up nucleosomes. The modifications regulate the way DNA is compacted in the nucleus, and recruit various proteins involved in activation or repression of gene expression. In CRC, many genes encoding of proteins responsible for these histone modifications are dysregulated, thus changing the epigenomic landscape of the cell. For example, histone deacetylase 2(HDAC2) is upregulated in the early steps of CRC. HDAC1-3, 5 and 7 have also been reported to be upregulated in CRC. Dysregulation of Lysine specific demethylase 1 (LSD1), which interacts with tumor suppressor p53, seems also to increase the proliferation, invasion and metastatic potential of CRC cells.

Non-Coding RNAs in CRC

Another type of epigenetic mechanism which can modulate gene expression in CRC is the non-coding RNAs which include the micro-RNAs (miRNA), and long-non-coding RNAs (lncRNA). For example, the miR-200 family are known to be implicated in cancer invasion and migration; the hox transcript antisense intergenic RNA (HOTAIR) is correlated to advanced CRC and enhanced metastatic potential of cancer cells.

Epigenetics is still a relatively new field of research. As scientists strive to elucidate the etiology of colorectal cancer, they discover new potential mechanisms at play. Understanding the epigenetic basis of CRC may open the door for new drugs and biomarkers, so be on the lookout!







References:

Bardhan, K., Liu, K., 2013. Epigenetics and Colorectal Cancer Pathogenesis. Cancers (Basel) 5, 676–713. doi:10.3390/cancers5020676

Sameer, A.S., Nissar, S., 2016. Epigenetics in diagnosis of colorectal cancer. Mol Biol Res Commun 5, 49–57.

Sazanov, A.A., Kiselyova, E.V., Zakharenko, A.A., Romanov, M.N., Zaraysky, M.I., 2016. Plasma and saliva miR-21 expression in colorectal cancer patients. J. Appl. Genet. doi:10.1007/s13353-016-0379-9

Vaiopoulos, A.G., Athanasoula, K.C., Papavassiliou, A.G., 2014. Epigenetic modifications in colorectal cancer: Molecular insights and therapeutic challenges. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease 1842, 971–980. doi:10.1016/j.bbadis.2014.02.006