Abstract
A report from the American Cancer Society reveals that colorectal cancer in people younger than 50 continues to increase, a trend that has spread to the 50-to-64 age group for the first time. Multiple lines of evidence indicate that obesity, often pinpointed as the cause, is not the only contributor.
According to a report from the American Cancer Society (ACS), colorectal cancer incidence is rising among younger adults even as the incidence of the disease has decreased in people age 65 and older.
Due in part to screening, the median age at diagnosis has dropped from 72 in 2001–2002 to 66 in 2015–2016. At the same time, incidence has been increasing in adults younger than 50 since the mid-1990s and, since 2011, in people ages 50 to 64.
“We don't know why rates are increasing in younger adults,” says Rebecca Siegel, MPH, of the ACS, lead author of the study. Even the best-known risk factors may not fully explain the trend.
The increased incidence among people ages 50 to 64 implies a birth cohort effect, meaning that individuals born during a span of time exhibit specific characteristics, such as increased risk for cancer, due to shared risk factors. “We're seeing a continuation of that birth cohort effect, because people who are younger and have a higher risk of disease don't just leave that risk behind them as they age. They carry it with them,” Siegel explains.
Obesity receives most of the blame. With obesity's prevalence growing in recent decades, it could be a culprit—and it's biologically plausible. Obesity is accompanied by physiologic effects that are linked to cancer development. For example, obesity can induce a chronic inflammatory state, and adipose tissue secretes inflammatory cytokines that can contribute to carcinogenesis, says Marc Gunter, PhD, of the International Agency for Research on Cancer (IARC). Altered glucose metabolism may also link obesity to colorectal cancer, with high levels of proproliferative insulin and related growth factors promoting tumorigenesis.
However, obesity does not completely account for the higher incidence of colorectal cancer, says Siegel, because increases in obesity have coincided with disease incidence rather than preceding it; the latter would be expected if obesity were the only cause. Further, the increased colorectal cancer incidence in younger adults isn't seen in black or Hispanic populations, despite upward trends in obesity in those groups.
Lower physical activity and more sedentariness are also risk factors for colorectal cancer that are increasing in younger adults. The biological mechanisms linking these factors to colorectal cancer are not fully understood, but in addition to their contribution to weight gain, people who are more physically active tend to have lower levels of insulin and insulin-like growth factor, improved immune function, and less inflammation.
Elevated levels of certain gut microbes and low microbial diversity are also associated with greater colorectal cancer risk and may contribute to the connections between diet, obesity, physical activity, and colorectal cancer. Furthermore, certain bacteria-derived compounds can leak into the colorectal mucosa. “[These chemicals] can promote inflammation that can lead to a microenvironment conducive to the development of colorectal cancer,” Gunter says. How changes in the gut microbiome specifically play a role in colorectal cancer remains unclear.
More data are needed to determine why the disease is increasing in younger adults. Gunter, IARC colleague Neil Murphy, PhD, and Peter Campbell, PhD, of the ACS are leading an effort on early-onset colorectal cancer using data and specimens from large-scale cohorts in the NCI Cohort Consortium to identify risk factors and biomarkers associated with colorectal cancer among more than 2,000 patients diagnosed before the age of 40.
“I think in the next 5 or 10 years,” Gunter says, “there will hopefully be more robust evidence that can help explain the rising trend in early-onset colorectal cancer.” –Nicole Haloupek
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