CCCF Research

At the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, several research studies were presented that shared a targeted approach to colorectal cancer (CRC) treatment that can ensure efficacy and reduction of side effects. The infographic below highlights those studies and their key findings.

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There is little known about the connection between various factors (such as environmental quality index, unmet needs, cancer survivorship, etc.) and the outcomes of patients affected by colorectal cancer (CRC). Studying the trends and associations around the onset and progression of CRC is integral to educating people on risk reduction. Additionally, using a disparity lens can aid decision-making processes and allow providers to target high-risk populations who may be in need of greater assistance and care. 

Several such studies were presented at the 2022 annual meeting of the American Society of Clinical Oncology. For example, Suleyman Yasin Goksu and team studied the association of young-onset CRC with the national level Environmental Quality Index (EQI). Their greatest finding? YOCRC can be linked to lower environmental quality. Additionally, Megan E. Delisle and team identified the association between unmet needs (in the physical, emotional, and practical sense) and survivors’ utilization of emergency services in the first three years following treatment. They found that a greater amount of unmet needs could be linked to higher utilization of emergency services–which is an issue that can be resolved through preventative measures. Both these studies reach important conclusions regarding how we draw patterns from disease. 

Here are some other studies from ASCO that dived into disparities and early-age onset CRC (EAO-CRC) outcomes:

  1. Disparity of treatment-related adverse events and outcome in patients with early-onset metastatic colorectal cancer (mCRC). With the marked rise of early-onset metastatic CRC (mCRC), there is a gap in diagnosis and adverse events related to treatment. Patient outcomes have not been conclusively studied, so Lingbin Meng and team reviewed the potential age-related disparity and its causes. Using individual patient data from three clinical trials in Project Data Sphere, patients were categorized into three age groups and sorted by adverse events. Patients younger than 50 had shorter median overall survival, higher incidence of toxicity (abdominal pain, severe anemia, and nausea/vomiting), but lower incidence of severe diarrhea, neutropenia, and fatigue. This group had the earliest onset of these adverse events and was associated with worse overall survival. Some of these disparities may be explained by distinct genetic profiles, but overall, patients with early-onset mCRC had worse outcomes and endured greater overall treatment-related adverse events. This study provides a basis for developing a personalized treatment plan when selecting patients for chemotherapy, providing counseling, and monitoring adverse events.
  2. Modifiable and non-modifiable risk factors associated with early-onset colorectal cancer: Analysis of the National Health Interview Survey. Risk factors for EAO-CRC are largely understudied, while on the other hand, there is a rapid increase in incidence. Hyeun Ah Kang and Yahan Zhang of The University of Texas at Austin studied modifiable and non-modifiable risk factors associated with the rise. Their cross sectional study analyzed data from the 2004-2018 National Health Interview Survey (NHIS). Individuals between the ages of 18 and 49 with a history of CRC diagnosis at the time of the interview were compared with their non-cancer counterparts. Additionally, the researchers also compared their nonage-related characteristics to those with late-onset CRC, meaning after 50. One hundred and fifty six patients with EAO-CRC were identified. Results from the comparisons showed that greater odds of EAO-CRC were associated with older age, living in the Midwest, and history of alcohol consumption. Lower odds were associated with Hispanic or Asian race and a lifestyle of vigorous physical activity. This study points to both modifiable and non-modifiable characteristics of EAO-CRC risk. Further studies can help identify the associated risk in-depth.
  3. Racial disparities in receipt of guideline-concordant care for early-onset colorectal cancer in the U.S. Black patients diagnosed with EAO-CRC have worse survival than their white counterparts, even in lieu of early-stage disease. Leticia M. Nogueira and team studied these racial disparities, with specific focus on guidance-concordant cancer care.The study included newly diagnosed non-Hispanic black and white individuals  between the ages of 20 and 49. Demographics, comorbidities, and insurance coverage were added to multivariable models to predict their contribution in the disparities with quality measures. Out of the 84,728 colon and 62,483 rectal cancer patients, 20.8% and 14.5%, respectively, were black. They were less likely to receive guideline-concordant care than white patients, which was primarily driven by insurance coverage rather than demographics or comorbidities. Overall, black patients received worse and less timely care than their white peers. Health insurance, a modifiable factor, was identified as the largest contributor to this gap. This study suggests that access to care can significantly influence EAO-CRC outcomes.
  4. Racial parity in rectal cancer treatment and outcomes within an integrated healthcare system. Hyunjee V. Kwak and team also looked at the survival outcomes of patients in the context of their race. They conducted a retrospective study of patients at the Kaiser Permanente Northern California health system, who were treated between 2010-2019. The study included over 3,500 patients diagnosed with rectal adenocarcinoma. Using self-reported race information, various analyses evaluated differences in race, age, stage of diagnosis, treatment, and overall survival. There was a greater proportion of Black patients with localized disease, who also had the longest overall survival. Hispanic patients were more likely to be male, younger, and have a shorter overall survival. These results show a gap in survival outcomes for patients treated at a large integrated healthcare system, where access to care is roughly equal. This calls for an improvement in outreach and screening, as well as awareness in these communities.
  5. Trends and disparities in the treatment of older adults with colon cancer. Half of the patients diagnosed with colon cancer are aged above 70, yet there is a huge gap in treatment for this population. Most are undertreated, perhaps due to age-related biases. Philip Q. Ding and team looked at age-related disparities in the realm of CRC care. Their retrospective, population-based study of adults diagnosed with CRC between 2010 and 2018 in Alberta, Canada included more than 10,000 patients, 48% of whom were over 70 years old. Upon further examination, it was found that older age correlated with more comorbidities and less advanced disease. Despite this, there was no statistically significant correlation between age and treatment status. As compared to the younger group, the odds of receiving surgery and systemic therapy were three and five times lower (respectively) among older patients. These two interventions continue to improve the outcomes of colon cancer in old and young patients alike, but the rates of treatment were lower in older patients and with minimal change over time. This study highlights a disparity in CRC care within the geriatric population.

Identifying these trends and disparities is just one step towards improved CRC care. It empowers patients to identify their personal risk and also gives their provider another factor to consider for treatment and prognosis. Understanding these correlations may be the next step in eliminating the gap in care for many populations.

 

Juhi Patel is a Colorectal Cancer Prevention Intern at the Colon Cancer Foundation.

Colonoscopy is the most effective test for colorectal cancer (CRC) screening and prevention. This procedure minimizes the incidence and mortality of colorectal cancer through early detection. During a colonoscopy, a physician inserts, and threads a flexible tube with a tiny camera called a colonoscope into the rectum and through the entire colon, or large intestine. This helps identify abnormal growths and excise any polyps which can then be sent for diagnosis.

However, research has shown that despite being the gold-standard for CRC screening, 23-30% of adenomas are overlooked and missed during a traditional colonoscopy, the success of which can vary depending on operator skills.

“Colorectal cancer is the second leading cause of cancer-related deaths in the United States and it is one of the few cancers that can be prevented if caught early,” said Aasma Shaukat, MD, MPH at NYU Grossman School of Medicine and the Robert M. and Mary H. Glickman Professor of Medicine and Gastroenterology and Director of Outcomes Research for the Division of Gastroenterology and Hepatology. “Our mission remains to improve and enhance the quality and efficacy of the colonoscopy across the board to provide the best care for patients.”  

In order to improve the efficiency and efficacy of colonoscopies, Dr. Shaukat and her team have developed an artificial intelligence (AI) platform to assist endoscopists. The findings of their  prospective, randomized, multicenter collaborative study to test the AI platform were recently published in the journal Gastroenterology. Between January and September 2021, twenty-two skilled, board-certified gastroenterologists performed colonoscopies on 1,440 patients. The patients were randomized to receive a traditional colonoscopy or a colonoscopy with computer-aided detection software —the software detects colorectal polyps during high-definition white-light colonoscopy procedures. This device can identify potential polyps and identify areas of concern, refining the results of the procedure in real-time. 

The researchers found that using AI during a screening colonoscopy increased the adenoma per colonoscopy rate by 22%: from 0.82 to 1.05. This evidence indicates that AI can be an effective and efficient tool for gastroenterologists and endoscopists to reduce the number of overlooked polyps left behind in the colon, many of which can be precancerous. 

Dr. Shaukat states, “Our findings add to the growing amount of literature that shows using computer-aided technology during an endoscopy procedure can improve the quality of exams performed and improve outcomes for our patients. Several software technologies are currently available for clinicians and incorporating the use of these resources will only enhance the care we provide our patients and improve the quality of exams we as physicians are able to perform.”

Sahar Alam is a Colorectal Cancer Prevention intern with the Colon Cancer Foundation.

With an observed increase of distant-stage colorectal cancer (CRC) among young patients in recent years, researchers have been searching for the reasons behind rising numbers and ways to counteract them. Carcinoids, a subtype of slow-growing cancer, have been found to contribute to the steadily rising incidence rate of early-onset colorectal cancer, which is diagnosed before the age of 50. This has created a need to assess the shifts toward distant-stage adenocarcinoma and its impact on public health.

Why Are We Seeing This Increase?

A study recently published in Cancer Epidemiology, Biomarkers & Prevention sought to understand how the proportions of distant-stage disease changed over time. Several studies have identified a significant increase (49%) in the average annual percent change for distant stage colorectal cancer in the 20-34 years age group. However, many of these studies do not report histological subtypes of CRC. 

With carcinoids increasing in younger patients, it is important to look at adenocarcinoma (most common cancer of the colon and rectum) staging independently from carcinoids (neuroendocrine tumors). Therefore, these researchers focused specifically on adenocarcinomas. Yearly adenocarcinoma incidence rates from the 2000-2016 Surveillance Epidemiology And End Results (SEER) data were stratified by stage, age, subsite, and race for 103,975 patients. Changes in the three-year annual incidence rate were calculated with the percent contribution of each cancer stage. Lastly, the subgroup with the highest proportion of distant-stage disease was determined.

The greatest percent increases were seen in distant-stage cancer when comparing data from 2000-2002 with 2014-2016. Here are a few significant findings of the study:

  • Colon-only distant adenocarcinoma increased most in 30-39-year-olds (49%)
  • Rectal-only distant-stage adenocarcinoma increased most in 20-29-year-olds (133%)
  • Based on race:
    • Distant stage proportions increased most for both colon- and rectal-only subsites in 20-29-year-old non-Hispanic Blacks (14% and 46%, respectively) 
    • The second most-impacted group was 20-29-year-old Hispanics with a 13% increase in the proportion of those affected by rectal-only, distant stage adenocarcinoma.

From these findings, we can conclude that the greatest burden of disease was on younger patients, highest in the non-Hispanic Black and Hispanic subgroups (despite relatively low absolute case counts). The researchers also uncovered that there is a decrease in early-stage disease in these early-onset groups. As we now know, younger patients are presented with higher risks, but the absolute incidence rates in the youngest subgroups remain relatively low.

These findings are important because they set a new precedent for patients under 50 who may not be aware that preventive screening for those at average risk of CRC starts at 45 years. Studies moving forward should also note that not all adenocarcinomas are categorized as early-onset CRC. Although this study is limited in its observational nature, it raises important questions in analyzing staging results, promoting screening opportunities, and keeping the general public aware of their risks. This study also presents potential solutions, including optimizing earlier screening and the risk-stratification of younger patients by family history and symptoms.

 

Juhi Patel is  Colon Cancer Prevention Intern.

Mom, wife, realtor, runner, cellist, and colon cancer survivor for five and a half years. Suzanne Miller was taken aback when she was diagnosed with Stage I colon cancer at the age of 40. Colorectal cancer screenings start at 45 years for average-risk adults. She was in good health, trained for marathons, and ate well. Luckily, she was able to undergo surgery on November 18, 2016, to remove the cancer. 

Suzanne realized she aspired to turn this event in her life into something good rather than dwelling on the fact that she had cancer. Since her surgery, on the 18th of each month, she spreads awareness by posting on Instagram and Facebook to remind individuals to “keep their rear in the clear.” Everyone who is over 45, under 45 with symptoms, or has a family history of colon or rectal cancer should get screened for colorectal cancer. Those with a family history of colorectal cancer should start screenings at 40 years or 10 years prior to the earliest diagnosis age in their family.

Survivor and Colon Cancer Awareness Advocate

Suzanne came across the Colon Cancer Foundation (CCF) while she was researching for a marathon to run in New York while raising money for a charity. She reached out to the Foundation and planned to run in the 2020 marathon, but it was canceled due to the COVID-19 pandemic. That didn’t dampen Suzanne’s spirit. She completed the marathon in her hometown and raised the money with support from her friends and family members who participated in the run. She looks forward to running again in the 2023 Colon Cancer Challenge.

This past February, as a CCF Champion, Suzanne and her husband were invited to attend the Cologuard Classic in Tucson, Arizona. She represented CCF and was able to meet 90 other like-minded individuals who shared her passion to make a difference and prevent early onset of colon cancer. Inspired to raise money and awareness in her hometown, Suzanne partnered with her husband’s golf club to hold a fundraising golf tournament on May 16, 2022. She was supported in her efforts by her friend, a 10-year colon cancer survivor who also works to spread colorectal cancer awareness. The event had 10 sponsors, 13 teams, and 20 hole sponsors that covered most of the costs. Half of the profits will go to their local nonprofit, CRC Life, and the other half will go to CCF.

Suzanne emphasizes that people need to be more comfortable discussing colon cancer, as they do other topics. Ever since she began raising awareness on social media, Suzanne has received messages from individuals when they received a colonoscopy, got a polyp removed, or discovered they have a family history of colon cancer. Through her experience as a young, healthy woman diagnosed with colon cancer, she brings attention to the fact that cancer does not discriminate. She always tells individuals to remind their friends and family to get a colonoscopy. “Even having one person find out that they do not have cancer is a win,” she says. Suzanne loves that we live in a world where we can speak our mind, while being kind and courteous, and have people that listen and don’t discount the matter at hand. 

 

Kenadi Kaewmanaprasert is an intern with the Colon Cancer Foundation.

In past years, the rate of colorectal cancer (CRC) has become a serious public health problem in Mississippi. A study conducted in 2020 showed that Mississippi had one of the highest mortality rates from CRC as well as one of the CRC lowest screening rates between 2015 and 2019. The state also leads the nation in cardiovascular disease mortality rates as well as diabetes mortality. These are both known comorbidities for many types of cancers, including CRC. 

One theory as to why the screening rates are so low in Mississippi is that about 55% of the state’s population resides in rural locations, which may make it hard for some individuals to access regular medical care. The rural population in Mississippi has a high rate of uninsured individuals making it hard for this population to afford regular screenings. In 2016, 14% of the population under 65 were uninsured. 

Another theory as to why CRC rates are so prevalent in Mississippi is that the diet of many of the residents is high in red meat and low in fiber. This is in part due to a culture that relies on red meat and processed foods. This diet is also more prevalent in areas that have a low socioeconomic background, as it can be difficult to obtain healthy food if one lives in a food desert. 

Colorectal cancer-related mortality in those over 50 (2014-2018).
Data source: https://statecancerprofiles.cancer.gov/map/map.noimage.php.

Fortunately, the Mississippi government recognized the issue and has developed a plan to help increase the screening rate of residents in Mississippi and decrease mortality rates 70X2020 was initiated in 2014. Since the start of the program, there has been an increase in individuals who got screened, specifically in minority communities. So far, screening rates have improved from 55% in 2014 to 69.9% in 2020. For white individuals there was a compliance rate of just under 70% and for black individuals there was a compliance rate of just above 70% in 2020. 

From this case study, we are able to theorize that screening and diet play a crucial role in the development of CRC. We are also able to see that there is a strong correlation between screening rates and CRC mortality rates. 

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.

In 2013, The Bourbon Mafia was formed when a group of bourbon enthusiasts and industry professionals came together in their search for rare bourbon. About a year in, they realized that they could utilize their platform to raise money for causes that are near and dear to their hearts. With 42 members spanning 11 U.S. states, and two members in Australia, the organization has raised approximately $150,000 since 2014  for various charities, including the Colon Cancer Foundation (CCF). The Bourbon Mafia raises money through events, including bourbon raffles, dinners, and bottle auctions.

Brian Gelfo, one of the founding members and the  treasurer and secretary of the Bourbon Mafia, spoke with the Colon Cancer Foundation about their organization’s motivation for donating to CCF. Omar Marshall was one of the first classes brought into The Bourbon Mafia. Following his diagnosis of colorectal cancer (CRC) in 2020, he and his wife, Pam Marshall, decided they wanted to raise awareness around this disease. The initial goal of The Bourbon Mafia was to donate in his honor while Omar was still with them. Unfortunately, Omar lost his battle with CRC on January 18, 2021.

Robert Diaz (second from left) receiving a donation from The Bourbon Mafia on behalf of the Colon Cancer Foundation.

Nevertheless, a $30,000 donation was made to CCF in April 2021. Before Omar passed, he participated in a selection of a Four Roses Bourbon barrel that would be used for the donation. Mr. Gelfo highlighted an impactful statement by Robert Diaz who represented CCF at the engagement event: “This $30,000 donation can fund 1,000 colon cancer screenings.” Members of The Bourbon Mafia were gratified that their efforts could impact the lives of a thousand people. “Even if one finds out early and gets treated, it’s well worth it,” Mr. Gelfo said. 

According to Mr. Gelfo, many members in the bourbon industry, including fans and supporters, are predominantly older men. Through these events, The Bourbon Mafia hopes to raise awareness in the community for them to get screened.

This year, their event was held on 25th February, 2022, in Louisville, Kentucky, where they expected to raise a minimum of $10,000. Barrels will be hand selected from Starlight Distillery and guests will receive a sample of bourbon, a beer, and a bottle of bourbon to take home. Silent auction items will be donated by Mrs. Marshall and the family as well as other distilleries.

Mr. Marshall was buried on the farm under an oak tree from where he can watch over the farm, as he always wanted to. Mrs. Marshall emphasized the importance of early detection and being proactive for any type of cancer. “The Bourbon Mafia and bourbon itself has brought me into contact with so many wonderful people who share the same passion for bourbon and helping others,” she said.

 

Kenadi Kaewmanaprasert is an 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.