Is late stage colon cancer on the rise in younger people?

• A recent study investigated changes in the incidence rates of colorectal cancer in individuals aged 20–55 years between 2000 and 2016.
• The study showed that individuals aged 20–39 years had the largest increase in advanced stage colorectal adenocarcinoma.
• The proportion of individuals with distant stage colorectal adenocarcinoma increased over the study period, whereas the proportion of those with early stage disease decreased.
• The increase rates of advanced stage colorectal cancer were greatest in young non-Hispanic Black and Hispanic individuals.
• This study highlights the importance of increasing awareness about the symptoms of colorectal cancer and early screening to facilitate early diagnosis.

A recent study published in the journalCancer Epidemiology, Biomarkers & Prevention suggests that the burden of distant or advanced stage colorectal cancer increased in younger individuals from 2000 to 2016.

The study involving individuals aged 20–55 years also found a negative link between age and the likelihood of presenting with distant stage early onset colorectal cancer (EOCRC). In other words, younger individuals were at the greatest risk of distant stage colorectal cancer.

The researchers reported an increase in the proportion of individuals with distant stage colorectal cancer among all racial and ethnic groups studied, but the trend was more pronounced in younger non-Hispanic Black and Hispanic individuals.

Dr. Neil Murphy, a scientist at the International Agency for Research on Cancer, part of the World Health Organization, said: “These and other recent data really highlight the urgent need for further research identifying risk factors for early onset colorectal cancer. Despite a growing number of studies in this area, risk factors for colorectal cancer in young adults remain largely unknown.”

“The study also reinforces the importance of those eligible for colorectal cancer screening from age 45 to get screened on time and for younger adults not to ignore any red flag symptoms — e.g., blood in the stool, abdominal pain, unintentional weight loss, plus others — and consult a physician. The earlier a cancer is diagnosed, the better the clinical outcome,” Dr. Murphy added.

Evaluating changes in colorectal cancer incidence

Previous studies have shown an increase in the average annual percent change for distant stage EOCRC, defined as colorectal cancer in individuals below the age of 50 years.

One of the objectives of the present study was to understand the changes in the contribution of distant stage disease to the overall number of EOCRC cases between 2000 and 2016. Evaluating this along with changes in the incidence rate can help estimate the burden of advanced stage colorectal cancer.

Another objective of the present study was to evaluate the changes in the incidence rates of colorectal adenocarcinomas, a specific subtype of colorectal cancer that accounts for the majority of colorectal cancers.

Significantly, in previous studies, researchers have pooled the rates of subtypes of colorectal cancers together, which the authors of this study claim can bias the estimated incidence of the different colorectal cancer stages.

Adenocarcinomas have been the focus of guidelines for screening and diagnosing colorectal cancers. Thus, it is important to independently assess the incidence rates of colorectal adenocarcinomas to better shape public health policies.

National Cancer Institute database

The present study analyzed data collected by the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program. The SEER program database provides demographically diverse data on cancer incidence and survival collected in 19 regions in the United States.

The researchers acquired data on annual colorectal adenocarcinoma incidence rates from 2000 to 2016 from the SEER database. Researchers analyzed data to compare age, cancer stage (in situ, localized, regional, and distant), and the tumor site.

• In situ carcinoma refers to abnormal cells that have not spread to nearby tissue.
• Localised describes cancer that is confined to the place where it started.
• Regional is where cancer has spread to nearby tissues, organs, or lymph nodes.
• Distant cancer has spread to different parts of the body.

Researchers classified the tumors according to location as colon-only, rectal-only, and combined colorectal cancers. Although EOCRC refers to people younger than 50 years, the researchers included individuals aged 50–55 years due to previous studies reporting an increase in incidence rates in this age group.

Increase in incidence rates

The researchers compared the 3-year average annual incidence rates of colorectal adenocarcinoma during 2000–2002 with those from 2014–2016. Among the different stages of colorectal adenocarcinomas, they observed the greatest increase in distant stage cancer during this period.

Comparing 2000–2002 with 2014–2016, the researchers found a 133% increase in distant stage, rectal-only adenocarcinomas in individuals aged between 20–29 years. However, this increase in the percentage of cancer incidence accompanied only a small increase in the absolute incidence rate. The incidence rate of rectal-only, distant stage adenocarcinomas in 20–29-year-olds increased from 0.06 to 0.14 cases for every 100,000 individuals.

Similarly, distant stage rectal-only and colon-only colorectal cancers rose by 97% and 49%, respectively, in individuals aged 30–39 years.

The researchers also found an increase in regional adenocarcinomas, especially at the rectal site. For instance, the incidence rate of regional rectal-only adenocarcinoma increased by 45% and 43% in individuals aged 30–39 years and 40–49 years, respectively.

Contribution of distant stage disease

The researchers found an increase in the proportion of distant stage colorectal adenocarcinomas in all age groups from 2000–2002 to 2014–2016. This was associated with a decrease in the proportion of in situ and localized adenocarcinomas in all age groups.

The study noted the largest increase of distant stage adenocarcinomas at the rectal subsite, which increased from 18% to 31% in individuals aged 20–29 years and from 20% to 29% in the 30–39 years age group from 2000–2002 to 2014–2016.

The researchers found a negative correlation between age and the likelihood of presenting with distant or regional stage colorectal cancer. Individuals aged 20–29 years had a 29% chance of presenting with distant stage disease, compared with 20% in individuals aged 50–55 years.

Distant stage colorectal cancer and race

During the study period, there was an increase in the proportion of distant stage cases for people of all racial and ethnic subgroups studied. However, the largest increase was in young non-Hispanic Black and Hispanic individuals.

Among non-Hispanic Black individuals aged between 20–29 years, there was a steep increase in the proportion of distant stage colon-only cancer, which rose from 20% to 34%, and rectal-only cancer, which rose from 0% to 46%.

Similarly, the proportion of distant stage, rectal-only cancers increased from 28% to 41% in Hispanic individuals aged 20–29 years. Although the proportion of distant stage colorectal adenocarcinomas increased in younger Hispanic and non-Hispanic Black individuals, the actual number of cases in these subgroups was lower than those observed in older individuals.

The study’s co-author Dr. Jordan Karliz, an associate professor at the University of Colorado School of Medicine and chief of the gastrointestinal (GI) division at Denver Health Medical Center, notes:

“We need to place additional focus on racial subgroups that have an increased tendency to present with distant stage disease, including the youngest non-Hispanic Black and Hispanic subgroups, to reverse these trends.”

Implications

Dr. Karlitz says: “These findings support the new guideline from the U.S. Preventive Services Task Force to begin average-risk screening at age 45 instead of 50. However, for those younger than 45, it is critical to act early on concerning symptoms to risk stratify for earlier testing.”

“Unfortunately, there are often long delays between symptom onset and diagnostic testing in young patients, which can increase the risk of ultimately being diagnosed with distant stage disease. Furthermore, it is essential that people know their cancer family history and that their healthcare providers routinely ask patients about their family histories because patients with a family history of colorectal cancer, and even other cancers, may need to begin screening well before the age of 45,” Dr. Karlitz adds.

Underlying causes

The study was observational in nature and not designed to identify the underlying causes for the increase in distant stage colorectal adenocarcinoma.

The study’s co-author, Dr. Eric Montminy, GI fellow at Tulane University School of Medicine, provided some potential reasons for the increase in early onset colorectal adenocarcinomas.

He said: “Although we are not exactly sure why rates of distant stage colorectal cancer are increasing over time, there are known risk factors for colorectal cancer, including early onset colorectal cancer, that we can help to address by pursuing healthy lifestyles. Obesity, sedentary lifestyle, increased consumption of sugary beverages, processed foods, alcohol and a number of other risk factors can be associated with colorectal cancer development.”

Similarly, Dr. Shuji Ogino, a professor of pathology at Brigham and Women’s Hospital, explained: “Early onset colorectal cancer diagnosed in patients under 50 years of age has been rising in the world without well-defined reasons. But scientific evidence gradually points to decades-long collective changes in “Westernizing” diet, lifestyle, and environment. Those changes actually affect nearly all of us, starting from the very earliest stage of our lives, even in our mother’s uterus.”

“Those dietary, lifestyle, and environmental changes in early life can influence the microbiota — such as bowel contents — and the development of the immune system. At the population level, younger generations may be more susceptible to many chronic adult diseases in their life course, and early onset cancer may be just the tip of the iceberg. We need to watch trends of chronic diseases across generations to find out,” added Dr. Ogino.

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