Race and Medicine

Race and Medicine

Issue: January, 2021
Disclosures: Anyane-Yeboa, Cercek, Eng,Raoof and Salem report no relevant financial disclosures.
January 25, 2021
14 min read
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Steady rise in early-onset colorectal cancer among Blacks calls for renewed outreach

Issue: January, 2021
Disclosures: Anyane-Yeboa, Cercek, Eng,Raoof and Salem report no relevant financial disclosures.
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Black individuals have the highest incidence and mortality rates of colorectal cancer of any racial or ethnic group in the United States.

Colorectal cancer is the third most diagnosed cancer in the U.S., with a 20% higher incidence among Black individuals compared with their white counterparts.

Normalizing conversations about family history of colorectal cancer is essential, according to Adjoa Anyane-Yeboa, MD, MPH.
Normalizing conversations about family history of colorectal cancer is essential, according to Adjoa Anyane-Yeboa, MD, MPH. “The two factors that are most predictive of an individual undergoing screening are receiving a recommendation from a medical provider and having a usual source of care,” she said.
Source: Massachusetts General Hospital.

Moreover, Black patients tend to present at a younger age and with more advanced tumors, and with a higher incidence of proximal colorectal cancer, which is known to respond poorly to standard treatment and has poorer outcomes.

As researchers have flagged an alarming increase of early-onset colorectal cancer generally, the disproportionate burden of this trend in the Black community is especially concerning, they said.

The death of “Black Panther” actor Chadwick Boseman, at age 43 years, brought about renewed awareness of these disparities in the U.S. and globally.

Although some of these differences can be explained by a lack of access to health care and screening and other socioeconomic issues, disparities persist after adjusting for these factors, experts said.

“We have known there to be a higher incidence of colorectal cancer in Black men and women and that it is also associated with increased mortality. Now thinking about young-onset disease, as well, makes things even trickier,” Adjoa Anyane-Yeboa, MD, MPH, gastroenterologist at Massachusetts General Hospital, said during an interview with HemOnc Today.

“It is unfortunate that the passing of Chadwick Boseman is what had to happen to bring increased awareness around colorectal cancer, but so many people have told me that after his passing they spoke with their family about it and learned that a relative had colorectal cancer, so they underwent screening,” Anyane-Yeboa added. “We need to ensure that Black men and women, who are at high risk for colon cancer, are being screened at age 45 years and that it is not only the people who have always been low risk that are continuing to get screened.”

HemOnc Today spoke with gastroenterologists and oncologists about the disproportionate incidence of colorectal cancer among young Black individuals, ongoing research into potential cancer risk factors in this group, recent updates to screening recommendations, and outreach efforts that are needed to address this worrisome trend.

Risk factors

Results of a SEER analysis published in 2019 in Gastroenterology showed the incidence of colorectal cancer among Black individuals between ages of 20 and 54 years increased from 11.7 per 100,000 people between 1992 and 1996 to 12.7 per 100,000 people between 2010 and 2014, compared with a corresponding increase of 7.5 per 100,000 people to 11 per 100,000 people among whites.

The absolute incidence of colorectal cancer appeared consistently higher across all stages among Blacks, mainly driven by a higher incidence of proximal colon cancer, according to the researchers.

Within the past decade, there has been growing recognition that early-onset colorectal cancer is on the rise, with a disproportionate increase in incidence among the Black population, Mustafa Raoof, MD, researcher in the department of surgery at City of Hope National Medical Center, said during an interview with HemOnc Today.

Mustafa Raoof, MD
Mustafa Raoof

“When looking at the incidence of colorectal cancer among Blacks vs. whites, there are approximately 40 cases per 100,000 white individuals, of whom 16 will die of colorectal cancer. For Blacks, the incidence is 49 per 100,000, and about 29 of these individuals will die,” Raoof said. “There is higher incidence among Blacks and a higher chance for death, which can be explained by the fact that colorectal cancer is diagnosed late and at a more advanced stage where treatments are not curative for many.”

There are a multitude of risk factors to explain this disparity, the most dominant of which is Black race, Raoof added.

“In many studies, being Black is a dominant risk factor for colorectal cancer, and this raises questions about race as a social construct with a lot of variables tied in,” Raoof said. “Black race could be a surrogate for socioeconomic status or social mobility, which are linked to well-being. It is not that there is something genetically problematic about being Black that leads to higher rates of colorectal cancer, it is that there are other environmental variables that play into the higher risk.”

Poor diet and obesity are other known risk factors.

Family history is yet another.

Data from a retrospective analysis published in Cancer showed colorectal cancer could have been diagnosed earlier or possibly prevented among adults aged 40 to 49 years had they undergone screening in accordance with family history-based guidelines.

One-quarter of those with colorectal cancer in this age group met criteria for family history-based early screening, of whom 98.4% could have been recommended to start screening at a younger age than the age at which they were diagnosed.

“There could also be genetic factors at play,” Anyane-Yeboa said. “One thing that I always think about with my patients is family history — patients knowing their family history and speaking openly about their family history. If a family member had colorectal cancer that was not talked about, then many individuals do not know that they are at increased risk and are not screened for it. Further, they may not know that they may have to be screened at age 40 year or younger.

“Providers should ask about family history and encourage patients to ask about it, as well,” she added.

Still, between 75% and 80% of colorectal cancers are sporadic and not genetic, according to Cathy Eng, MD, FACP, FASCO, David H. Johnson chair in surgical and medical oncology, director of the Young Adults Cancer Initiative and co-leader of the Gastrointestinal Cancer Research Program at Vanderbilt University Medical Center.

“The median time frame from when an individual experiences symptoms to when they are diagnosed is about 6 months, and many do not have a family history of colon cancer,” Eng told HemOnc Today. “Not only do these individuals not have a family history, but they also appear healthy and are not necessarily aware of the symptoms of colorectal cancer, which is why they are present later and with more advanced-stage disease.”

Cathy Eng, MD, FACP, FASCO
Cathy Eng

Although inherited cases of colorectal cancer are historically known to involve right-sided tumors, Eng said there may be an increase in left-sided tumors and rectal carcinomas that will be led by cases in young adults.

“This is exactly what I am seeing in my clinic today,” Eng said. “However, it is still important to know that we may have patients with a right-sided tumor who may be younger, and we know that right-sided tumors, if stage IV or metastatic, have significantly lower survival.”

The microbiome also is presumed to have a role in the increased incidence of colorectal cancer among young Black patients.

“In some ways, the microbiome as an emerging factor at play in early-onset colorectal cancer is underappreciated,” Raoof said. “The bacteria that normally reside in the colon have a huge impact on colorectal cancer incidence. A lot of research groups are interested in and looking at early-onset colorectal cancer and how the microbiome differs in early-onset vs. late-onset disease, and how it specifically differs among Black vs. white patients.”

Researchers have only just begun to scratch the surface of the determinants of colorectal cancer in Black individuals, Raoof added.

“We will see a lot of new data coming out on this within the next 10 years,” he said. “Having a better understanding of what leads to early-onset colorectal cancer among Blacks could pave the way for better treatment strategies. There is something fundamentally different about the microbiome, the host or the tumor itself among Black and white patients. If we can identify what those differences are, then we may be able to design better strategies for screening and treatment.”

Screening recommendations

Based on the observed incidence of colorectal cancer in younger adults, the U.S. Preventive Services Task Force released a draft recommendation in October that reduced its recommendation to start colorectal cancer screening from age 50 to age 45 years — regardless of race.

The task force acknowledged that Black adults are more likely than other populations to be diagnosed with colorectal cancer and to die of the disease and encouraged clinicians to recommended colorectal cancer screening to their Black patients beginning at age 45 years.

“Although the task force is not a part of the U.S. government, their guidelines are the most stringent and most followed by primary care physicians,” Raoof said. “Insurance companies also are more likely to reimburse for screening procedures based upon USPSTF recommendations. Moving the recommended screening age to 45 years is associated with a lot of costs, so the benefit needs to be certain.

“The new recommendation is grade B, which is still a good recommendation, but is not as strong as a grade A recommendation,” he added. “Screening earlier is a step in the right direction, but it is not certain that it is cost-effective on a national level.”

Even with the lower age recommendation, screening could remain underutilized among young Black individuals.

“Screening earlier makes sense — it is probably the most important intervention that we have right now, but the uptake of guidelines takes a while,” Raoof said. “It may be several years before we start to notice that the earlier age recommendation has been adopted. It is important to note that the guideline may be disproportionately adopted due to implicit bias among physicians treating these patients. There is growing evidence to show this.”

In 2018, American Cancer Society also released guidance supporting 45 years as the age to initiate screening, although the American Gastroenterology Association still recommends age 50 years.

Adjoa Anyane-Yeboa, MD, MPH
Adjoa Anyane-Yeboa

“It is important for all people to be screened, but changing the screening age will not necessarily increase access to screening and it does not ensure those who need to be screened earlier will be,” Anyane-Yeboa said. “It could potentially mean that low-risk individuals will be screened more, which may increase the gap even more. Studies looking into racial and ethnic differences in screening uptake for those aged 45 to 50 years, particularly since the American Cancer Society changed their guideline, could be beneficial because it has been a couple of years since those guidelines were released.”

Black individuals historically have been recommended to start colorectal cancer screening at age 45 years based upon the known higher incidence and worse outcomes, Andrea Cercek, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, said during an interview with HemOnc Today.

Andrea Cercek, MD
Andrea Cercek

“Due to the rising incidence of early-onset colorectal cancer, the screening recommendation has officially been lowered to age 45 years, which is great and is a good place to start because most patients are diagnosed between the age of 40 and 50 years,” Cercek said. “However, many minorities are diagnosed in their 20s and 30s — the steepest rise is among the 20- to 30-year age group, and this includes men, women and nonminorities, as well.”

However, reducing the recommended age to 20 years would create a vast population of people who would require screening, she added.

“This is a very big area of research right now, to identify what factors are contributing to this rise and beyond that, to identify the individuals at highest risk,” she said. “What is it about their genetic makeup that may predispose them to develop cancer, and is there an unidentified environmental risk factor?” Eng agreed.

“While it is a step in the right direction to have the colorectal cancer screening age reduced to 45 years, it is important to keep in mind that there has been a steep rise in incidence among those aged 20 to 34 years. Even though the screening age has been dropped, we will miss out on patients because some are still too young to be screened,” Eng said.

“There is a very fine line in trying to decide whether to make the recommended screening age even younger than 45 years,” she added. “We should make it younger because it takes 5 to 10 years for a polyp to become cancerous and if a patient comes to the clinic at age 45 years, theoretically, that polyp that was originally not cancerous would have been there starting at the age of 30 or 40 years.”

Given that screening is not recommended for younger groups, advocacy and awareness will be key.

“Lowering the recommended initial screening age from 50 to 45 years is a definite step in the right direction and will likely lead to early detection and diagnosis of colorectal cancer among individuals aged 45 to 49 years; however, this policy change will have no impact on patients aged younger than 45 years of age at diagnosis for whom the increase in incidence rates are the among the highest,” Mohamed E. Salem, MD, associate professor of medicine and gastrointestinal medical oncologist in the department of solid tumor oncology at Levine Cancer Institute at Atrium Health, told HemOnc Today. “Hence, raising awareness of colorectal cancer symptoms through education and implementation of programs to improve access to care and early diagnostic strategies among younger adults, especially those with low socioeconomic status, is critical to early-stage diagnosis.”

Genetic testing

Not only is early-onset colorectal cancer on the rise, but it also tends to be diagnosed at advances stages, complicating treatment and outcomes.

“Patients with early-onset colorectal cancer often present with advanced-stage disease at diagnosis compared to older patients, perhaps because colorectal cancer is least expected in younger individuals,” Salem said. “Initial symptoms are often attributed to other etiologies, lack of awareness and recognition of symptoms; inherent shame at presenting with symptoms such as diarrhea and apparent anal bleeding; limited access to health care, particularly among patients with low socioeconomic status; and inability to afford necessary treatment, all of which can lead to later stage presentation and delayed diagnosis.”

Researchers are looking into genetic characteristics of tumors that present in younger Black adults to identify whether a difference in disease biology may account for the more aggressive disease and higher mortality rates observed in this group.

In a study published in Clinical and Translational Gastroenterology, Staudacher and colleagues examined the potential differences in somatic mutations between Black vs. white patients with sporadic colorectal cancer.

Researchers found KRAS mutations occurred less frequently among white vs. Black patients (OR = 0.64; 95% CI, 0.53-0.76), whereas mutational differences in BRAF and PI3CA did not reach statistical significance. KRAS mutations in particular are associated with poorer prognosis in sporadic colorectal cancer, which may contribute to the higher mortality observed among Black patients, according to the researchers.

“This is an area ripe for improvement and research is ongoing,” Cercek said. “We are participating in research on genetic sequencing along with some of our local institutions in the New York area and across the country that serve a more diverse population. It will be important to see if we can identify a difference in the actual tumor genetics or whether there is increased exposure to an environmental factor that is universally causing these tumors to form at a much younger age than they used to.”

Genetic testing is important to guide treatment, but patients from historically underrepresented groups tend to have lower testing rates, compounding their disparities.

For instance, data presented last year at American Association for Cancer Research Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved showed lower rates of testing for microsatellite instability (MSI) and mismatch repair deficiency (MMR) among vulnerable groups.

Researchers used the National Cancer Database to pool data on 45,326 patients newly diagnosed with advanced colorectal cancer between 2010 and 2016 and found 26.5% of patients (n = 11,998) underwent MSI and MMR testing.

Results showed testing appeared less common among Blacks compared with whites (adjusted OR [aOR] = 0.87; 95% CI, 0.82-0.94); patients who were uninsured (aOR = 0.78; 95% CI, 0.7-0.86), Medicaid-insured (aOR = 0.87; 95% CI, 0.8-0.94) and Medicare-insured (aOR = 0.87; 95% CI, 0.81-0.93) compared with privately insured; and among those diagnosed at a community (aOR = 0.6; 95% CI, 0.56-0.66) or comprehensive community cancer program (aOR = 0.76; 95% CI, 0.72-0.8) compared with those diagnosed at an academic or NCI comprehensive cancer program.

“Genetic testing is used to look at the genetic makeup of the tumor to see if there is a distinction between the tumors that are early-onset, and then we are able to take a deeper dive into racial and ethnic differences to see if there may be differences within the young adult early-onset group and whether the tumors of Blacks look different than those of other races,” Cercek said. “This information is limited, which is probably due to limited access to academic centers that perform genetic testing and potentially limited access to health care in general. What we can tell is that studies to date have not shown a significant difference between early-onset tumors among minorities vs. whites, but the numbers are very limited, unfortunately. We do not have the adequate power to answer this question right now.”

Lower rates of genetic sequencing may also be attributed to insurance coverage.

“Insurance does cover the basic screening for Lynch syndrome, which is the most common cause for colorectal cancer in young people. However, most insurance [companies] have not factored age alone into approving genetic testing based upon age, so it is still tricky to perform genetic testing in the younger population,” Cercek said. “We also do not know for certain that minorities have decreased rates of genetic screening, even thought my thought is that they do. There most likely is a disparity here, largely based upon health care access.”

Raising awareness

Experts with whom HemOnc Today spoke agreed that raising awareness is key in reducing the colorectal cancer disparities seen among young Black individuals.

“The biggest and most important thing right now is to raise awareness — outreach is hugely important,” Cercek said. “At our institution, we have a specific center for patients with early-onset colorectal cancer. A mission and goal of ours is to do more community-based outreach to spread the word among minorities that if they are in their 20s and 30s and have symptoms, to please seek medical care immediately.”

It also is imperative that primary care providers are aware of and do not dismiss colorectal cancer symptoms, Cercek added.

“We have seen from surveys, such as the Colorectal Cancer Alliance survey, that patients have reported symptoms to an average of three medical providers before undergoing colonoscopy, which eventually diagnosed their colon cancer,” Cercek said. “Raising awareness among the young adult population and physicians is the most important thing to do at this point.”

Anyane-Yeboa agreed and said an awareness campaign around discussing family history also is important.

“In some families it can be taboo to ask and talk about family history, but normalizing these conversations is so important,” Anyane-Yeboa said. “Also, the the two factors that are most predictive of an individual undergoing screening are receiving a recommendation from a medical provider and having a usual source of care. So, we also need to encourage providers to recommend screening to ensure that patients have access to health care and that providers are recommended screening to all of their patients.”

Providers should also offer different types of screening currently available, Anyane-Yeboa added.

“Everyone always thinks about colonoscopy, but we have many different options now, including stool-based testing, like fecal immunohistochemical tests or stool DNA tests, and CT colonography. Granted, colonoscopy is the gold standard, but at the end of the day, the best test is the test that gets done,” Anyane-Yeboa said. “If a patient does not want to undergo colonoscopy — some studies have shown concern in the Black community about colonoscopy, particularly among men — it is important that providers are offering other options.”

Eng said continued awareness and outreach about screening is critical.

“Individuals should listen to their bodies, including when they are young,” Eng said. “We know when something is not normal with our body, and it is so important to speak to a medical provider about it. Also, know your family history and always remember that colorectal cancer for the most part is preventable as long as we catch it early.”

Ensuring that the Black community has proper access to health care is also key.

“We still have a lot of Black individuals in this country who are uninsured and cannot undergo screening procedures or see a primary care physician to recommend a screening procedure. This is truly a bottleneck, but is somewhat of an easy fix at the policy level,” Raoof said.

Still, a lot of unknowns remain about early-onset colorectal cancer, he added.

“Even among the physician community, most recognize that there is a rise in early-onset colorectal cancer, but physicians work in silos,” he said. “Some do not have access to underprivileged groups and may not appreciate how disproportionality colorectal cancer affects minorities. By highlighting the issue more and presenting this information to the right audience, it will hopefully set into motion a movement to overcome this unfortunate disparity.”

References:

Augustus GJ, et al. Am J Pathol. 2018;doi:10.1016/j.ajpath.2017.07.023.

Gupta S, et al. Cancer. 2020;doi:10.1002/cncr.32851.

Iorgulescu JB, et al. Abstract PO-091. Presented at: American Association for Cancer Research Virtual Meeting: The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Oct. 2-4, 2020.

Murphy CC, et al. Gastroenterology. 2019;doi:10.1053/j.gastro.2018.11.060.

Staudacher JJ, et al. Clin Transl Gastroenterol. 2017;doi:10.1038/ctg.2017.48.

USPSTF. Draft recommendation statement. Colorectal cancer: Screening. Available at: www.uspreventiveservicestaskforce.org/uspstf/draft-recommendation/colorectal-cancer-screening3. Accessed Dec. 31, 2020.

For more information:

Adjoa Anyane-Yeboa, MD, MPH, can be reached at Massachusetts General Hospital, 55 Fruit St., Boston, MA 02115; email: aanyane-yeboa@mgh.harvard.edu.

Andrea Cercek, MD, can be reached at Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065; email: cerceka@mskcc.org.

Cathy Eng, MD, FACP, FASCO, can be reached at Vanderbilt University Medical Center, 777 Preston Research Building, 2220 Pierce Ave., Nashville, TN 37232; email: cathy.eng@vumc.org.

Mustafa Raoof, MD, can be reached at City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA 91010; email: mraoof@coh.org.

Mohamed E. Salem, MD, can be reached at Levine Cancer Institute, 1021 Morehead Medical Drive, Charlotte, North Carolina, 28204; email: mohamed.salem@atriumhealth.org.