The Colon Cancer Foundation (CCF) spoke with Dr. Rami James Aoun, 11th winner of the Dr. Thomas K. Weber Colorectal Cancer Research Scholar Award, for his work looking at biomarkers of radiation response in rectal cancer patients. He is a surgical resident at The Ohio State Wexner Medical Center. Instituted in 2011 by CCF and the Society of Surgical Oncology to recognize translational research focused on the molecular biology of colorectal cancer, the award was renamed in 2020 to honor CCF’s founder, the late Dr. Thomas K. Weber.

Born in West Palm Beach, Florida, Dr. Aoun was raised in Beirut, Lebanon, where he was a student at the American University of Beirut. After completing his undergraduate years and medical school, Dr. Aoun joined Columbia University in New York where he received a Master of Public Health degree in Healthcare Management and Policy. As part of his ongoing residency at The Ohio State Wexner Medical Center, he is completing a research fellowship with Dr. Matthew Kalady, a colorectal surgeon at The James Cancer Center.

Dr. Rami James Aoun

Q: What motivated you to work in the oncology research space, and colorectal cancer in particular?

Dr. Aoun: I am motivated to work in oncology research because I have seen some of my own family members suffer from cancer. However, what specifically interests me in colon cancer research are the patients that I encounter here at The James Cancer Center and my mentors. Their guidance when I was a junior resident was extremely important to set the direction for me as a future colorectal surgeon. That’s how I met Dr. Kalady, and now I am a part of his lab conducting research on colorectal cancer, with the goal of improving patient care outcomes.

Q: Can you summarize the significance of your findings for which you have received this award? Can you also share the prior work or observations that laid the foundation for this project?

Dr. Aoun: We observed a difference in how patients with rectal cancer reacted to neoadjuvant radiation therapy. Some of the patients who were exposed to neoadjuvant therapy had a complete response—the cancer disappeared. However, there were patients who had almost no response to the therapy. The response can be determined and graded by examining the tumor under a microscope. Patients who had a better response end up living longer without cancer.

We sought to identify the reason certain cancers responded to neoadjuvant radiation and certain cancers did not. To do that, we tried to understand these cancers at the genetic level by studying how a rectal cancer expressed particular genes, as measured by mRNA. By comparing the gene expression in both, patients who responded to radiation therapy and those who did not, we were able to obtain a gene signature that helps us identify patterns of gene expression that are different between responders and non-responders.

While this is just a starting point, it can help us develop a more predictive model to use clinically. Once we validate this model, we could be able to distinguish between a responder and non-responder to radiation based on the gene expression that we obtained from their biopsies even before any treatment is administered. This would allow us to provide individualized patient-specific therapy and avoid any unnecessary treatments and procedures.

We also think that certain genes in this signature can be further studied to see if they might be able to be blocked or changed to improve the response to treatment.

Q: What was the size of your current cohort and what is the ‘n’ that you are looking for to be able to validate your study results?

Dr. Aoun: Our ‘n’, or sample size, was 33 patients for this study. In genetic studies like this, it is difficult to design a statistical power needed to validate, but we hope to test this in about 100 different patients.

Q: Did you see any commonality in the gene signatures between rectal cancer and colon cancer?

Dr. Aoun: The gene signature we investigated was related to radiation resistance in rectal cancer, whereas colon cancer is not usually treated with radiation therapy. So, we did not study this for colon cancer. However, some of the pathways we identified are known to be relevant to colon cancer. In terms of the common pathways, what we know is the WNT pathway specifically is involved in the development and progression of colon cancer and rectal cancer. In the gene signature that we identified, six of the genes are involved in the WNT pathway. So, the question is whether the WNT pathway is also involved in radiation resistance in rectal cancer.

Q: Rectal cancer has been steadily increasing in the younger population. Do we know why that may be happening?

Dr. Aoun: An increasing number of younger patients are being afflicted with colorectal cancer and we don’t fully know why. There are lots of different theories about diet, lifestyle, and the microbiome (i.e. the bacterial content in the colon and rectum). This is a hot area of research and many groups are trying to figure out this question.

 

A study published in the Journal of Medical Economics simulating a cohort of one million Medicare patientsUS adults aged 65 years and olderwith average risk of colorectal cancer, investigated the cost-effectiveness of non-invasive fecal tests (fecal immunochemical test (FIT), fecal occult blood test (FOBT), and multi target stool DNA test (mt-sDNA)). The researchers used the Colorectal Cancer and Adenoma Incidence and Mortality Microsimulation Model (CRC-AIM) with test-specific adherence data to estimate the cost-effectiveness of the various options.

Assuming 100% adherence follow-up colonoscopies and using real-world screening adherence data, the researchers found that mt-sDNA was cost-effective when compared to FOBT but not FIT. Cost-effectiveness was defined at the $100,000/quality adjusted life-year (QALY) threshold. 

  •     $62, 814/QALY when compared to FIT
  •   $39,171/QALY when compared to FOBT

The assumption of100% adherence to follow-up colonoscopies is not a significant limitation to this study because this is just one scenario and also because follow-up colonoscopies are covered under Medicare. Since follow-up colonoscopies are covered under Medicare there is not a financial disincentive to get a colonoscopy and therefore most people under Medicare do get the colonoscopy.  Moreover, when the authors ran the model using real-world follow up-colonoscopy and screening adherence rates, they found that mt-sDNA was even more cost-effective:

  •   $31,725/QALY when compared to FIT
  •   $28,465/QALY when compared to FOBT

Generally an incremental cost-effectiveness ratio (ICER) of less than $100,000 is considered good value, and those under $61,000/QALY is considered cost-effective. Therefore, when real-world adherence rates were considered, mt-sDNA was the more cost-effective option compared to both FIT and FOBT and resulted in greater reductions in CRC incidence and mortality.

Cost-effectiveness analyses are important for determining which screening test performs better than the others, and where to relocate resources to achieve the best health outcomes for the lowest possible cost. These types of studies on Medicare populations are important because they help policy makers make informed decisions on resource allocation.

 

Gargi Patel is a Colon Cancer Prevention Intern with the Colon Cancer Foundation.

We learn time and again that prevention is the best medicine, and this holds true for colorectal cancer (CRC). It is estimated that 50% of CRC cases can be prevented with diet and lifestyle modifications. Previous studies that looked at the relationship between CRC development and nutrition concluded that there is a strong correlation between diet and the development of certain types of cancer, specifically CRC. 

A recent study published in Preventive Medicine Reports investigated the impact that an insufficient diet plays in the development and prevalence of certain cancers as well as the effect that race and ethnicity has on diet.  Wholegrains, dietary fiber, non-starchy fruits, and vegetables, dairy products, milk, cheese, dietary calcium, coffee, and calcium supplements were found to be associated with preventing cancer development. The study examined population attributable factors and the number of excessive cases diagnosed in Texas in 2015 that were attributed to an inadequate diet, defined as a diet that does not meet or conform to the national or global dietary recommendations. 

With a diverse study population, the researchers had the opportunity to explore how race and ethnicity play into diet and thus contribute to the prevalence of cancers, specifically colorectal cancer (CRC).  

The study found:

  • While men were more likely than women to not follow guidelines on red and processed meat consumption.
  • Women were more likely to miss dietary recommendations on fiber and calcium intake.
  • A significant correlation between processed meats consumption and the prevalence of CRC and a connection between red meat consumption and the prevalence of CRC. 

There has been additional research conducted to show that there is a link between dietary fiber intake, and dietary calcium intake and the prevention of CRC. Looking at the racial and ethnic difference the study found that Non-Hispanic Whites consumed higher than the recommended dietary intake of red and processed meats. While it was found that Non-Hispanic Blacks were the most likely to have insufficient fiber and calcium intake.

In the Texas population, the authors found:

  • 3.3% of all new cancers (>3,428) could be attributed to an inadequate diet 
  • 34% of new CRC cases can be attributed to dietary insufficiencies 

The authors describe a similar correlation identified in an Australian population, where:

  • 17.6% of CRCs were related to an insufficient fiber level in diet 
  • 17.7% of CRCs were attributed to red and processed meats 
  • Men had a higher proportion of cancers attributable to an insufficient diet than women 
  • Excess consumption of processed meat contributed to 1,002 new cancer cases and red meat consumption contributed to 379 additional cancer cases 

This study along with multiple other studies conducted in relation to dietary factors and their contribution to cancer highlight the importance of dietespecially insufficient fiber intake and excess red or processed meat intakeon overall cancer burden.

 

Abigail Parker is a Colon Cancer Prevention Intern with the Colon Cancer Foundation.

Immunotherapy aids your immune system to fight off cancer. There are five types of immunotherapy: treatment vaccines, immune checkpoint inhibitors, T-cell transfer therapy, monoclonal antibodies, and immune system modulators. While there have been no treatment vaccines approved for colorectal cancer (CRC) yet, BioNTech’s mRNA-based treatment vaccine has recently reached phase 2 clinical trials for CRC. The vaccine, individualized to each patient, is being developed as a treatment for CRC as well as to prevent relapse in those who have undergone CRC surgery. 

How Does Immunotherapy Work?

The immune system is built to detect and destroy abnormal/mutated cells. Tumor-infiltrating lymphocytes are often found around tumors and they are an indication that the immune system is working to eliminate the tumor. Cancer cells typically undergo genetic changes that allow them to escape the immune system—they often have proteins on their surface that inactivate immune cells, and they can even change cells surrounding them to interfere with the immune system. Therefore, a therapy that can train the immune system to identify and destroy cancer cells capable of defying the immune system is important.

Cancer Treatment Vaccines

Cancer treatment vaccines are designed for people who already have cancer, and trains their body’s immune system to find well-hidden cancer cells. These vaccines can be made in three different ways. 

  1. From the patient’s own cancer cells to cause an immune response against features that are unique to their cancer.
  2. From tumor-associated antigens that are found on cancer cells. These are made for cancer subtypes.
  3. From dendritic cells, which are a type of immune cell that respond to an antigen on tumor cells. This type of a vaccine is already being used for treating prostate cancer.

Matias Riihimäki et al. in their 2016 epidemiologic study published in Scientific Reports found that up to 18% of all CRC patients have recurrence and up to 25% have metastasis. A treatment vaccine would be able to help prevent recurrence and help patients with metastasis suppress small tumors that are often difficult to remove surgically.

BioNTech Chief Medical Officer and Co-founder Özlem Türeci, M.D., noted in a press release, “This trial is an important milestone in our efforts to bringing individualized immunotherapies to patients. Many cancers progress in such a way that the patient initially appears tumor-free after surgery, but after some time tumor foci that were initially invisible grow and form metastases. In this clinical trial in patients with colorectal cancer, we aim to identify high-risk patients with a blood test and investigate whether an individualized mRNA vaccine can prevent such relapses.”

Gargi Patel is a Colon Cancer Prevention Intern at the Colon Cancer Foundation.

Slow-transit constipation (STC) is reported to occur in 15-30% of people in the U.S. The most widely accepted definition of STC is two or fewer bowel movements per week or straining at stool more than 25% of the time. Research continues to point to STC as a risk factor for colorectal cancer (CRC).

A study published in 2020 that looked at 2,165 patients (median age 54 years), found that the cumulative probability of CRC was 0.2% 5 years after STC diagnosis and 0.4% 10 years after STC diagnosis. This was not significantly different (p=0.575) than among those without STC diagnosis. However, this may be due to the small number of patients (5) who were diagnosed with CRC.

Although the authors of the 2020 study did not find a significant difference among those with and without STC diagnosis, it is well established that STC increases CRC risk. Gurérin et al. in their 2014 study of over 100,000 patients identified a statistically significant risk of CRC among those with STC:

  • 56% higher for CRC
  • 260% higher for benign neoplasm
  • 256% higher for benign neoplasm in colon
  • 262% higher for anal and rectal polyps

Current management options for STC range from dietary counseling, pharmacological therapy, and surgery. 

While the etiology of STC remains unclear, there is increasing evidence that it is caused by an imbalance in the gut microbiome. Zhang et al. in their 2021 review published in Gastroenterology Report found that gut microbiota may play a major role in modulating colonic motility, secretion, and absorption. However, there is still much research needed to understand how the gut microbiome modulates movement of fecal matter through the small intestine and colon.

Conversations about the role of the gut microbiome in CRC development were a part of the Early-Age Onset Colorectal Cancer Summit held by the Colon Cancer Foundation in May 2022.

 

Gargi Patel is a Colon Cancer Prevention Intern with the Colon Cancer Foundation.

 

Much of the illness trajectory in cancer patients is strongly associated with symptom management during—and maybe even years after—chemotherapy treatment. Though chemotherapy drugs are the more common  mode of cancer treatment, along with surgery and radiation, patients may experience side effects associated with their quality of life.

According to a study published by the Paediatrics and Child Health Journal, supportive care during intensive chemotherapy is credited with improvements in overall morbidity and mortality rates in adults and children. Symptom and pain management may be classified as supportive care for patients in active treatment. While chemotherapy-related side effects can be anticipated, it is rather challenging to predict if the effects will be mild, moderate, or severe. Of the 236 cancer patients studied in the article, the effects ranged sporadically and were individually unique.

Supportive care methods and recommendations were addressed during a recent CURE Educated Patient Metastatic Colorectal Cancer Webinar hosted by speakers Nina N. Grenon, DNP, AOCN; Amber S. Norton, RN, BSN, OCN; and Kelley A. Rone, APRN, BSN. Speaking from their clinical and patient experiences, the care providers agreed that chemotherapy treatment may look different on a day-to-day basis, but the key, according to Ms. Grenon is “to make adequate adjustments” and to “dose adjust, rather than hold out from continuing treatment.” The expert panelists encouraged patients to communicate as much as they can with their providers, so that dose adjustments, paint management, or overall symptom management can happen early, rather than letting it get to the point where their cancer treatment needs to be paused.

Appetite suppression and fatigue are the most common side effects of a chemotherapy regimen, and the research article emphasizes that this can coincide with other symptoms such as nausea or vomiting, which is typically experienced by almost half the patients receiving chemotherapy.

The panelists noted that appetite suppression and fatigue directly correlate with each other; if a patient does not eat, then they will be fatigued or if a patient is fatigued then they will not want to eat. In order to break this cycle, they recommend:

  • Smaller meals
  • Flavoring water
  • Foods that will not increase nausea
  • Keeping the mouth moist
  • Setting an alarm to eat

Most importantly, patience is a crucial element to any treatment regimen. Encouraging the patient to eat whatever they can throughout the day is a great place to start. “You don’t have to eat three meals a day…eat what you can throughout the day, even if you just eat small bites all day long, at least you’re getting something opposed to nothing,” Norton reassures. With that, following up with a nutritionist and maintaining communication with your provider can make all the difference. Having a holistic approach to care rather than isolating focus on specific symptoms tends to provide a less challenging segway into survivorship and healing.

Assessment and identification of sources of distress in cancer patients provide an opportunity to improve quality of life during care and restoration of dignity. Adequate communication amongst the patient’s care team will allow the patient to make good progress and respond well to the primary treatment, while also ensuring that their quality of life is maintained.

Slow-transit constipation (STC) is reported to occur in 15-30% of people in the U.S. The most widely accepted definition of STC is two or fewer bowel movements per week or straining at stool more than 25% of the time. Research continues to point to STC as a risk factor for colorectal cancer (CRC).

A study published in 2020 that looked at 2,165 patients (median age 54 years), found that the cumulative probability of CRC was 0.2% 5 years after STC diagnosis and 0.4% 10 years after STC diagnosis. This was not significantly different (p=0.575) than among those without STC diagnosis. However, this may be due to the small number of patients (5) who were diagnosed with CRC.

Although the authors of the 2020 study did not find a significant difference among those with and without STC diagnosis, it is well established that STC increases CRC risk. Gurérin et al. in their 2014 study of over 100,000 patients identified a statistically significant risk of CRC among those with STC:

  • 56% higher for CRC
  • 260% higher for benign neoplasm
  • 256% higher for benign neoplasm in colon
  • 262% higher for anal and rectal polyps

Current management options for STC range from dietary counseling, pharmacological therapy, and surgery. 

While the etiology of STC remains unclear, there is increasing evidence that it is caused by an imbalance in the gut microbiome. Zhang et al. in their 2021 review published in Gastroenterology Report found that gut microbiota may play a major role in modulating colonic motility, secretion, and absorption. However, there is still much research needed to understand how the gut microbiome modulates movement of fecal matter through the small intestine and colon.

Conversations about the role of the gut microbiome in CRC development were a part of the Early-Age Onset Colorectal Cancer Summit held by the Colon Cancer Foundation in May 2022.

 

Gargi Patel is a Colon Cancer Prevention Intern with the Colon Cancer Foundation.

 

The Colon Cancer Foundation’s Lakshmi Yeturu sat down (virtually!) with Dr. Brian Dooreck to find out more about his initiative to arm newly diagnosed colorectal cancer patients and caregivers with substantial resources as they bravely face their diagnosis and treatment. Part I of this interview can be found here.

 

Can you tell us more about the mission of the Colorectal Cancer Provider Outreach Program (CRC POP) ?

The premise is quite simple. Provide our patients with guidance and direction to the support that is available to them at the time of diagnosis at the bedside.

 

If a newly diagnosed patient approached you for support, how would you describe CRC POP to them?

The Colorectal Cancer Provider Outreach Program is designed to provide you access to nationally available support organizations, their websites and phone numbers, to call them, connect with them, engage with them, lean into them, pull from them, share with them, and get whatever support you and your family need. There’s no monetization, there’s no hope, there’s no sale, and there’s no email being collected—there’s nothing more than just providing direction to you at the time of diagnosis to reinforce that you’re not alone and to provide you with the support you need here and now.

 

What kind of resources do you look to arm them with?

  • For their mobile phone, texting the word ‘COLON’ to 484848
  • All our providers have the ability to put a PDF on their website
  • All our providers have the ability to put an order in their electronic medical records

And that’s all that’s needed…there’s not much more to it. The providers are being given the simplest of tools to lead patients to a centralized web page, centralized PDF, and a centralized text number to give patients direction.

 

Does CRC POP seek to provide resources for caregivers and loved ones as well?

As I mentioned earlier, of the 150,000 people diagnosed with colon cancer every year, every diagnosis has a family member or a support system around them. So, if you take that number and extrapolate it out, every person that is affected may affect, on average, three or five or six other people. Do the math and that number becomes a lot more than 150,000. We expect that  very soon, the support that we are providing at the time of diagnosis can not only help the patient and their family but also promote screening and prevention for those organizations that have preventive screening programs

 

How has CRC POP progressed since it was founded? In your opinion do you think patients will seek POP as a resource for comfort or information following their diagnosis?

his idea was conceived in May or June of 2020; we had initial calls in July, drafted it and we launched on October 1st. We are now in a position where CRC POP is set up, it is up and running and we are in the process of sharing it with GI providers through social media.

Our goals are to connect with the three GI Associations, to find tools through them, through the National Colorectal Cancer Roundtable and the American Cancer Society. In addition, we want to connect with endoscopy centers. I am all about finding the outcomes and results we need to get to the providers quicker, faster, and easier.

I’m not going to be cold calling. Instead, we have started by getting about 10 of the largest groups aware of this and signed onto it in principle, including Gastro Health and GI Alliance. About 1200 GI doctors represented by those 10 groups now know what we’re doing and it’s now about ‘How do you utilize what is there?’

 

Personally, do you associate the terms ‘comfort’ or ‘information’ with the aims of CRC POP? Or is there another term you think better resonates the mission of CRC POP?

The missions are for me clearly ‘reassurance and support’. I would say reassurance and support at the time of diagnosis, provided by the doctor to the patient.

 

Do you feel like this program will make a real-world impact on the scale of patient information access?

 My goal is to measure it every month and to know how many clicks, how many calls each of these organizations are getting because you’re suddenly taking the active, potential user of a resource and providing them with the information in their hands. If it helps one person feel more reassured, more secure and they get the information they need then it is serving its purpose. That’s my goal, to have increased utilization month to month to month by the 14,000 gastroenterologists in the country.

 

In short, your goal is to measure how this is impacting the patients that you, your partners, or the gastroenterologists that have signed on to this program are diagnosing, and to eventually put this out there so every single board-certified gastroenterologist who can diagnose colorectal cancer introduces their newly diagnosed patient to CRC POP?

Ideally, that would be wonderful because we’re diagnosing the cancer and we’re sending the patient home. And this is how it goes: we diagnose someone and 10 minutes later I’m doing a procedure on another patient and that person is home in a cold panic, not understanding, clouded, diagnosed, Googling ‘Am I going to die from colon cancer?’ What I’m doing is providing reassurance at the time of diagnosis that gives them the guidance they want and need through whatever resources they choose to tap into. What the organizations do, what happens from that point of contact is between the organizations and the patient or the person reaching out. What I’m doing is providing people the direction.

 

So, what you are saying is that you are being there for the patient even when you’re physically not there for them after they’ve been diagnosed?

Yes, correct, I’ll see them in two weeks but in that two-week window, a lot of things need to be done. They need to get labs, they need to see a surgeon, they need to see an oncologist, they need to get a CAT scan. But besides that, I’m not there for them. They will call my office maybe but imagine having a 24/7, 1-800 number to call to speak to someone, to have a group to join, a community to have. Have their questions answered on things like ‘Am I going to die?’

In these cases, people’s world is thrown upside down, their blueprints in life are ripped up, and that’s kind of what we are trying to provide support for in the simplest of terms. Leveraging free technology and helping people.

 

Lastly, I just wanted to conclude on an open-ended note. For those within the non-scientific/medical community, do you think that this program will pave the avenue to improve the scale of information made available to patients after they are diagnosed?

I mean the level of information available from these organizations is huge and the level of information they provide is not just clinical, emotional, financial, academic, research, or trial-based. The level of advocacy, lobbying, or opportunity they can provide people is probably so individualized that it’s not measurable. So, I think that the potential of what happens from the contact made by a person—be it a patient, their family member, or their caregiver—with any of these organizations is truly dependent on what they want or need from it and what they express their needs to be. I can almost guarantee you that any organization that is not able to provide that assistance or that direction will say, ‘Listen, we’re really good at this we are excellent at that, but we don’t know anything about that. You know who does? This organization. Ask for this person, here’s the phone number.’ That’s what will happen.

 

If so, could you describe why it is imperative to support the large-scale sharing of medical information that ensures that all patients are adequately informed about their diagnoses?

Well, I wouldn’t say it’s imperative in the sense that the medical care is not going to get affected in theory. But in terms of imperative to providing the highest quality of care, no doubt. Imperative to providing the most empathetic role as a provider and position, no doubt. Imperative in improving people’s quality of life and sharing something to help someone else at a level that’s not technical, cold, calculated, or that can be measured in a medical chart. That’s imperative. The role of this is imperative because it’s not us who’s being told we have colon cancer and I always say it could be one in a million but you’re that one it’s a 100%.

That’s where I see the role of this program and the reality is it just takes a little courage and a little change in a little shift in mindset of the gastroenterologist to get a new part of their working algorithm or new part of their process into play. You get into their knee jerk response: I diagnose colon cancer, I tell the patient to text 484848, type in the words ‘COLON’, remind them resources are available right now.

 

 

 

A study conducted by researchers in Japan found that cigarette smoking may increase the risk of colorectal cancer (CRC) incidence in a Japanese population While smoking has been associated with an increased risk of CRC among Western populations, it has not been investigated as a risk factor in Asian populations prior to this study, according to the authors.

 

Statistics show that 60% of CRC cases occur in developed countries and CRC incidence continues to increase rapidly in Asia. Specifically, Japan experienced an increase in cases from 1978 to 1993 and has remained stable since then but is still among the top 10 countries with the highest incidence of CRC. A separate Japanese study found a gender-based difference in CRC incidence, with men being more susceptible to rectal cancer and women being more susceptible to colon cancer:

 

Colon cancer:

  • Men: 65.7%
  • Women: 75.4%

Rectal cancer:

  • Men: 34.3%
  • Women: 27.0%

 

It is hypothesized that environmental and lifestyle factors, such as smoking, can increase the risk of CRC. In Japan, for instance, 80% of men and 20% of women were smokers in the 1950s. However, a significant reduction was observed in smoking rates by 2017: only 32% of men and 9% of women were smokers. The age-standardized CRC incidence rate was 22.2 in 1978 and 38.9 in 2018.

 

Tobacco use can cause many different cancers, including mouth, larynx, lung, kidney, liver, and many more . In 2014, the U.S. Surgeon General’s report added CRC to the list of tobacco-related cancers. However, there are some issues with this:

  • Evidence supporting the claim that the use of tobacco is associated with the development of colon cancer has been derived mainly from Western populations while data from Asian populations are conflicting. More research is needed on this association in Asian populations.
  • Meta-analysis by geographic region did not find a significant association between smoking and CRC in Asian studies

The Japanese study aimed to investigate the correlation of smoking and CRC incidence in Asian populations.

 

Researchers used original data from major cohort studies performed by the Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan. The following criteria  were used when examining these studies for this analysis:

 

  • Population-based cohort studies conducted in Japan
  • Studies initiated between the mid-1980s and mid-1990s
  • Studies with more than 30,000 participants
  • Studies that acquired information on health-related lifestyles
  • Studies that followed the incidence of CRC

 

A self-administered questionnaire at the baseline survey determined if each participant was a smoker and classified them into one of three groups: never smoker, former smoker, or current smoker. Participants were followed-up for CRC incidence from the baseline study until the date of CRC diagnosis, migration out of the study area, death or the end of follow-up, whichever was first. The end of the follow-up period was between December 31, 1992 and December 31, 2014.

 

The study found that men who were ever, current or former smokers had a statistically significant higher risk of CRC than never smokers. Ever and current smoking increased the risk of both colon and rectal cancer, while former smokers had an increased risk of colon cancer.

Women who were ever, current or former smokers did not have an increased risk of CRC, but a significantly greater risk of distal colon cancer. Women who were heavily exposed to smoking had an increased risk of CRC.

 

Colon cancer is one of the most preventable diseases through screening methods and avoiding risk factors such as smoking , obesity, and poor diet. The American Cancer Society recommends getting screened at age 45 or younger if you have a family history of CRC.

A large cohort study that evaluated Swedish family inpatient and outpatient cancer registries found that those who had diabetes had an increased risk of colorectal cancer (CRC)—the magnitude of risk was similar to having a family history of CRC.

The study had a long timeline and follow-up was conducted between 1964-2015. The 12,614,256 individuals included in the study were born after 1931; 559,375 of them had diabetes and 162,226 had CRC. The authors queried the risk of developing CRC among those who had diabetes and found that:

  • 9-fold greater risk of CRC before 50 years among those diagnosed with diabetes before 50 years (range, 1.6-2.3)
  • 9-fold higher risk of CRC before age 50 years among those diagnosed with diabetes before 50 years who also had a family history of CRC (range, 4.1-12)
  • Lifetime risk of CRC before age 50 years among diabetic patients (0.4%) was similar to those with just a family history of CRC (0.5%). It was double that of the average population (0.2%).

This study confirms the positive association between early-onset diabetes and early-onset CRC and makes a case for earlier CRC screening among young adults with diabetes.

Results from the South Australian Young Onset (SAYO) CRC study identified a similar correlation between personal and family history of diabetes and CRC risk. The study cohort included 50 unrelated young adults up to age 55 years diagnosed with CRC (23-54 years), and 253 controls without CRC (18-54 years). Personal and family history of diabetes was documented in this entire population. The study found:

  • 24% of CRC patients also suffered from type II diabetes compared with 5% of the control group
  • 51% of young adults with CRC had at least one first-degree relative with type II diabetes
  • All patients with a personal history of type II diabetes also had first-degree relatives with type II diabetes
  • 44% of CRC patients under 45 years and 60% of CRC patients 45-54 years had a first-degree relative with type II diabetes

These findings create a very strong case for raising awareness among young adults with diabetes of their increased risk of early-onset CRC, especially if there is a family history of diabetes, so they can initiate CRC screening earlier than the USPSTF recommendation of 50 years.