When you have blood drawn in a routine doctor’s visit, some of the markers that get tested could hold unexpected clues to how likely you are to develop colorectal cancer at a young age, new research suggests. Adults younger than 45 who had lower levels of two liver enzymes – aspartate transaminase, or AST, and alanine transaminase, or ALT – were more likely to be diagnosed with early-onset colorectal cancer compared with their peers in an analysis released Wednesday by Epic Research, which is owned by the health-care software company Epic. “The direction was a little counterintuitive. Clinically, we tend to watch for high liver enzymes, so seeing that low AST and ALT were associated with a higher likelihood of early-onset colorectal cancer stood out,” said Kersten Bartelt, a clinician and researcher at Epic Research who worked on the new analysis. But doctors say that younger adults with low AST or ALT shouldn’t panic and that there’s no change to colon cancer screening recommendations. The new research highlights an association but does not mean that low levels cause cancer or that people should rush to get an early colonoscopy due to low levels alone. Rather, the findings – which have not been published in a peer-reviewed journal – suggest an area to investigate to better understand the potential underlying factors in the rise in colorectal cancer among younger adults. “Our study shows the association but wasn’t built to uncover why,” Bartelt said. “Clinically, low AST and ALT can reflect things like lower muscle mass, frailty or nutritional factors. It’s one of the questions we hope this work prompts others to investigate.” The new findings are striking since higher levels of AST and ALT are sometimes a sign of an unhealthy liver, and certain conditions such as liver diseases or infections can cause elevated levels. These markers are often included in routine blood testing because elevated liver enzymes may serve as early warning signs of liver injury, inflammation or disease, even before symptoms appear. “AST and ALT aren’t values we’d advise anyone to try to raise,” Bartelt said. “And nothing in our study suggests that changing them would change a person’s cancer risk,” she said. “They likely reflect underlying physiology like muscle and nutritional status, so the focus should be on overall health in partnership with your clinician, not on moving a single lab number.” Along with examining AST and ALT levels, Bartelt and her colleagues examined triglyceride and cholesterol levels, as well as levels of potassium. They found that none of the other routine labs were associated with early-onset colorectal cancer. Cancer rising among younger ages The question of why colorectal cancer cases are increasing among younger adults has been an ongoing one within medicine. Colorectal cancer has surpassed other types to become the leading cause of cancer deaths among people under 50 in the United States. “Whenever there’s a focus on colon cancer, particularly early-onset colon cancer, we need to figure out why. There’s definitely been an increase in early-onset colon cancer, and if there are markers that point us towards the right patients to screen, that’s great,” said Dr. Marc Fenster, a gastroenterologist at Episcopal Health Services in New York who was not involved in the new research. “The broader conversation surrounding early-onset colorectal cancer has focused on family history and genetics, obesity and metabolic health, diet, physical inactivity, the microbiome, antibiotic exposures and delays in recognizing symptoms in younger patients. However, none of these factors fully explains the increase in cases,” Fenster said. “This study may broaden the discussion by suggesting that routinely collected metabolic and nutritional markers could contain useful clues.” Fenster added that although the research points to a “signal” and is “hypothesis-generating,” it does not establish low AST or ALT as risk factors for early-onset colorectal cancer. “The study should encourage research, but it should not change how an individual patient is screened,” he said. “I don’t want people to think they have a low AST or ALT, then all of a sudden, that means they’re going to have colon cancer or they even need to do anything differently,” he said. “If you don’t have a family history, if you’re having zero symptoms, if you’re healthy, you’re not losing weight, you’re not having rectal bleeding, then this study doesn’t change my approach to that.” In the United States, the clinical guidance is that everyone at average risk start screening for colorectal cancer at age 45. People at higher risk — because of things like their own health history, a family history or symptoms — may start screening earlier. And blood testing is already an option to screen for colorectal cancer. In May, for the first time, the American Cancer Society added blood-based screening tests to its list of recommended choices for adults 45 and older who are at average risk of colorectal cancer and who have not completed or who have declined visual exams and stool tests. The blood-based screening test the group recommends is the Shield test, which is not a part of routine blood work. Colonoscopies are still considered the gold standard for screening, and blood testing is not the first choice for patients. Also, a positive Shield blood test is not a final diagnosis; the patient must follow up with a timely colonoscopy. Blood-based tests “do not replace colonoscopy in any way,” Fenster said. Generating ‘worthwhile’ questions To uncover what routine lab results may be associated with early-onset colorectal cancer, Bartelt and her colleagues analyzed health data on more than 11,000 people between the ages of 18 and 44 across the United States. Each adult had their first colorectal cancer screening test between 2017 and 2025 and had at least one AST or ALT test in the three years prior to screening. But since regular screening for colorectal cancer is not recommended until age 45, it was unclear why patients included in the analysis had a colonoscopy or other screening test. It could have been due to a family history, symptoms or other factors putting them at high risk. “I would suspect that these patients are coming in with some sort of symptom, and they’re having a diagnostic colonoscopy other than a screening colonoscopy,” Bartelt said. The researchers analyzed the data from adults who were diagnosed with colorectal cancer within a year of the screening and compared it with data from the adults who were not diagnosed with the disease. The analysis showed that adults whose AST levels fell below 14 units per liter of blood had a 65 per cent higher likelihood of an early-onset colorectal cancer diagnosis compared with peers who had levels in the range of 14 to 29. Similarly, adults whose ALT levels were below 14 had a 68 per cent higher likelihood than their peers. In contrast, higher AST levels – 30 or above – were associated with a 22 per cent lower likelihood of being diagnosed with colorectal cancer, and ALT levels of 30 or above were associated with a 29 per cent lower likelihood. The researchers said they used the levels of 14 to 29 as comparison values because they fell within the midrange of the levels observed in the new analysis. “Clinically, these enzymes vary from person to person and can shift over time with things like activity level, muscle mass, illness or medications,” Bartelt said. The researchers also looked closely at AST and ALT levels that shifted over time, specifically those that rose in the three years before the adults were screened for cancer. The data showed that rising AST was associated with a 27 per cent lower likelihood of colorectal cancer and a rising ALT with a 26 per cent lower likelihood, compared with adults whose values held steady. Decreasing AST or ALT levels showed no significant association in either direction with colorectal cancer. Still, what are considered “normal” levels of AST or ALT can vary within medicine in general. While each diagnostic lab may have its own reference range for how “normal” levels of AST and ALT are measured, “the AST and ALT levels described as ‘low’ in this study would generally be regarded clinically as normal values,” Dr. Daniel Sussman, leader of the gastroenterology high-risk prevention clinic at the University of Miami Health System’s Sylvester Comprehensive Cancer Center, said in an email. “That makes me particularly cautious about suggesting that these laboratory results represent an abnormality or a meaningful colorectal cancer risk marker,” wrote Sussman, who was not involved in the new research. “Unexpected findings can certainly generate worthwhile research questions, but they also require particularly careful validation.” Could the liver hold clues? A separate study published in the International Journal of Cancer also found that higher levels of AST and ALT, still largely within the normal range, were associated with a lower risk of colorectal cancer. The research was based on more than 375,000 people in the United Kingdom who provided blood samples in 2006 to 2010. That study had a different focus than the new analysis: It assessed how liver enzyme levels may be associated with longer-term risks of colorectal cancer, while the new analysis examined whether routine blood tests could flag undiagnosed early-onset colorectal cancer. But despite their differences, both papers showed an inverse relationship between ALT and AST levels and colorectal cancer, or CRC. “The findings, plus our prior ones on overall CRC, highlight the need to further understand both the etiological and predictive role of liver functional changes in CRC,” Mingyang Song, an associate professor at Harvard T.H. Chan School of Public Health, who was an author of the previous study but not involved in the new analysis, said in an email. “In our study, participants were generally healthy and thus had AST/ALT levels largely within the normal range. Among these people, lower levels may reflect reduced functionality and metabolic capacity of the liver, which may indicate a greater susceptibility to toxins and carcinogens,” Song wrote. “Such susceptibility may translate to a greater risk for CRC.” But he added that clinical recommendations should not be made based on AST or ALT levels alone. Bartelt agreed that a low AST or ALT result on its own is not a cause for alarm. “Additional research is needed to determine how low AST or ALT values should factor into early screening recommendations,” Bartelt said. “My recommendation is to stay up to date on recommended screenings – routine screening at age 45 for average-risk adults and earlier with symptoms, family history or other risk factors – and to talk through your specific situation with your care team.” Sussman added that he would not recommend that anyone attempt to increase their AST or ALT levels and that the new research does not change clinical guidance around screening for colorectal cancer. Overall, he would not recommend screening for adults younger than 45 solely based on their AST or ALT values. Rather, “the analysis appears exploratory,” Sussman wrote. “At this point, I believe the appropriate response is further investigation rather than changing how clinicians interpret normal liver enzyme levels or how we determine who should undergo colorectal cancer screening.” One of the questions the new findings raise for follow-up research is: “How does this generalize to a broader population?” said Caleb Cox, head of research at Epic, who oversaw the team behind the new analysis. The increase of colorectal cancer cases at younger ages is “an emerging area where there aren’t a lot of answers,” Cox said. “We don’t think these low levels are the cause. They can help point towards maybe there is something that is causing the AST and ALT levels to be lower that is also the underlying driver of the rise in colorectal cancer among younger adults.”
