A new analysis provides much-needed empirical evidence to support recent recommendations from the American Cancer Society and the US Preventive Services Task Force to start colorectal cancer (CRC) screening at age 45.

Initiating lower gastrointestinal endoscopy in younger women was associated with a significantly reduced risk for CRC. For instance, researchers found that starting endoscopy before age 45 lowered the risk for incident CRC by 63%, and starting between ages 45-49 lowered the risk by 57% compared with those who did not receive an endoscopy.

“Our findings support guidelines from the past 4 years that recommend screening for CRC at 45 years of age,” lead author Wenjie Ma, MD, ScD, Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues, write.

The study was published online today in JAMA Oncology.

Although cases of CRC have decreased in recent decades, experts have observed a steady increase in CRC diagnoses among people under age 50 — a group for whom routine screening was not recommended until recently.

In 2018, the American Cancer Society recommended CRC screening begin at age 45 rather than 50 for average risk individuals, and the US Preventive Services Task Force followed suit in 2021 with the same recommendation.

The recommendation was based on the benefit vs burden estimated using microsimulation models of CRC screening in a hypothetical cohort of 40-year-olds. But until now, “scant” empirical evidence existed on the potential benefits of screening in younger populations, the study authors said.

In the current analysis, the researchers explored the association between endoscopy initiation at younger ages and CRC risk among US women.

The study included 111,801 women from the Nurses’ Health Study II who were age 26-46 years at enrollment (median age, 36 years). Over 26 years, 519 incident cases of CRC were documented.

In the multivariable analysis, lower GI endoscopy was associated with a significantly lower risk of incident CRC when screening started before age 45 (hazard ratio [HR], 0.37), between 45 and 49 years of age (HR, 0.43), 50 to 54 years (HR, 0.47) and 55 years or older (HR, 0.46) compared with no endoscopy.

The absolute reduction in the estimated cumulative incidence of CRC through age 60 was 72 per 100,000 when endoscopy started at 45-49 years of age vs age 50-54.

The researchers also analyzed initiation of endoscopy in 299 younger-onset CRC cases that were identified. Compared with no endoscopy, starting endoscopy before age 45 was associated with a 55% lower risk of CRC diagnosed before age 55 (HR, 0.45). Starting endoscopy between ages 45-49 and between ages 50-54 was also associated with a significantly reduced risk of CRC diagnosed before age 55 (HR, 0.43 and HR, 0.50, respectively).

Notably, endoscopy initiated before age 50 was not associated with risk of dying from CRC, but the small number of deaths from CRC in this younger cohort limited the power for the mortality analysis.

Although the investigators conclude that their analysis supports current guidelines to start CRC screening at age 45, they acknowledge that the analysis only included women and mostly White healthcare professionals, which limits the generalizability of the findings.

Moving forward, it’s “critical to conduct future studies in more representative and inclusive populations so that the results are generalizable to the experience of all individuals at risk for developing colorectal cancer,” according to the authors of an accompanying editorial.

The editorialists also note that all age groups could benefit from improved CRC prevention efforts and access to screening.

“With the existing CRC screening recommendations now in place for individuals aged 45 years or older at average risk of CRC, other critical questions as to the real-world comparative effectiveness, uptake, and adherence to different forms of CRC screening in younger individuals deserve attention and further research,” they write.

Funding for the study was provided by the National Institutes of Health (NIH). Ma has received support from the Massachusetts General Hospital (MGH) Executive Committee on Research Tosteson and Fund for Medical Discovery Postdoctoral Fellowship Award, and an American Gastroenterological Association Research Scholar Award outside the submitted work. A complete list of authors’ disclosures is available with the original article. Editorialist Gregory S. Calip, PharmD, MPH, PhD, owns stock in Roche and has received grants from Pfizer.

JAMA Oncology. Published online May 5, 2022. Abstract, Editorial

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