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Published in final edited form as: Gastroenterology. 2021 Oct 29;162(3):964–965.e3. doi: 10.1053/j.gastro.2021.10.039

Increasing Incidence Rates of Colorectal Cancer at Age 50–54 Years

Timothy A Zaki 1, Amit G Singal 1, Folasade P May 2, Caitlin C Murphy 3
PMCID: PMC8881296  NIHMSID: NIHMS1752847  PMID: 34757141

Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality in the U.S. Incidence and mortality rates have decreased in older adults since the early 1990s. In contrast, incidence rates have risen among younger adults (early-onset CRC, age <50 years), from 8.6 per 100,000 in 1992 to 12.9 per 100,000 in 2018.

Several recent studies demonstrate that incidence rates of early-onset CRC have increased successively across generations.1, 2 Persons born in and after the 1950s and 60s, now entering mid-adulthood, are increasingly at risk of CRC, with even higher incidence rates observed in younger generations, including Generation X (approximate birth years 1965–1980) and Millennials (approximate birth years 1981–1996). This so-called “birth cohort effect” has been discussed frequently in the literature and formed the basis of both revised screening guidelines3 and studies evaluating potential causes of early-onset CRC.

As generations mature, they will carry with them an elevated risk of CRC, raising the possibility that incidence rates will begin to increase at older ages, such as persons older than age 50 years. For example, higher rates of lung cancer incidence and mortality among persons born in the 1920s and 30s, first observed in the early 1980s, continued to increase through the late 1990s.4 To determine whether this same phenomenon exists for CRC, we examined trends in incidence rates for ages 45–49, 50–54, and 55–59 years in a population-based sample.

We used data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program to estimate age-specific (45–49, 50–54, and 55–59 years; individual ages between 50–55 years) incidence rates per 100,000 persons during the period 1992 – 2018, overall and in approximate 4-year intervals. To account for the possibility that incidence rates may increase due to increasing uptake of CRC screening over time, we estimated age-specific incidence rates by stage at diagnosis. See Supplementary Methods for details.

There were 101,609 incident diagnoses of CRC (age 45–59 years) during the period 1992 – 2018. Between 1992–95 and 2016–18, incidence rates increased from 23.4 to 34.0 per 100,000 persons for age 45–49 years and from 46.4 to 63.8 per 100,000 persons for age 50–54 years (Figure 1). Conversely, incidence rates decreased for the 55–59-year age group, from 81.7 to 63.7 per 100,000 persons. Because of this opposing trend – or decreasing rates for age 55–59 years and increasing rates for age 50–54 years – incidence rates for the two age groups were nearly identical in 2016–18 (Figure 1).

Figure 1.

Figure 1.

Age-specific incidence rates of colorectal cancer, by 4-year interval, SEER 13, 1992–2018

Supplementary Figure 1 shows age-specific incidence rates by stage at diagnosis. For ages 45–49 and 50–54 years, incidence rates of local, regional, and distant disease increased from 1992–95 to 2016–18. For example, rates of regional disease increased from 17.6 to 21.5 per 100,000 persons for 50–54-year-olds, and there was a similar, although smaller, increase in distant disease. Rates of local, regional, and distant disease decreased for the 55–59-year age group.

Supplementary Figure 2 shows incidence rates for ages 50, 51, 52, 53, 54, and 55 years. Increases in incidence rates for these ages differed by time period, consistent with a birth cohort effect. For example, for age 51 years, incidence rates began to increase in 2000–03, but the increase occurred later (2016–18) for age 54 years.

We observed a clear pattern of increasing incidence rates of CRC for adults in their early 50s, supporting our hypothesis that incidence rates will increase at older ages as higher-risk generations mature. A recent meta-analysis similarly found prevalence of advanced neoplasia in 45–49-year-olds (3.6%) approached that of 50–59-year-olds (4.2%);5 others have reported steep increases in incidence rates from age 49 to 50 years, which may reflect preclinical, undetected disease at younger ages.6 Increasing incidence rates are likely not driven by earlier detection via screening. Although increasing prevalence of endoscopy may, in part, account for increasing rates of local disease, our findings illustrate that rates of distant disease have also increased.

Increasing incidence rates of CRC in 50–54-year-olds parallel the well-documented increases in early-onset CRC,7 and the same, as-yet-unknown mechanisms contributing to increasing incidence rates at ages younger than 50 years may also contribute to increasing rates in this age group. These mechanisms remain puzzling because most young adults diagnosed with CRC have no known risk factors or predisposing conditions.7 The birth cohort effect1, 2 provides clues – risk factors in early life or accumulated across the life course likely play a role. These risk factors may affect early and late stages of the carcinogenic process, manifesting as both early-onset CRC and increasing rates of CRC at older ages.

Despite the availability of and recommendations during our study period to initiate average-risk screening at age 50 years, incidence rates of CRC – of all stages – increased at age 50–54 years. Screening has increased in this age group over time but lags behind older age groups, prompting calls for more intensive efforts to increase on-time screening.8 More recently, the U.S. Preventive Services Task Force9 joined the American Cancer Society3 to recommend average-risk screening begin at age 45 (vs. 50) years. It is not yet clear whether these recommendations will translate into a lesser burden of disease, but if the pattern that we observed at age 50–54 years is similar for age 45–49 years, new guidelines may not be sufficient in mitigating increasing incidence rates in 40-year-olds.

New guidelines to initiate screening at age 45 years, combined with the increasing incidence rates at age 50–54 years that we have reported here, illustrate the importance of considering age at diagnosis as a continuum (vs. early- or later-onset). For example, recent work shows a continuum of molecular and mutational changes across age, whereby CRC diagnosed in the “youngest young” is distinct from CRC in middle age, which is additionally distinct from older age.10

In summary, increasing incidence rates of CRC at age 50–54 years parallel increases in early-onset CRC, and the same mechanisms likely contribute. Trends in incidence over the next decade (i.e., whether incidence rates start to increase in adults aged 55–59 years) will provide empiric evidence to either support or contradict our observations.

Supplementary Material

1

Grant support:

This work was supported by the National Cancer Institute at the National Institutes of Health under award number R01CA242558. The sponsor had no role in: design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Footnotes

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Disclosures: AGS reports consulting for Exact Sciences and Bayer. CCM and FPM report consulting for Freenome.

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Supplementary Materials

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