Low liver enzyme levels linked to colorectal cancer in adults under 45, but screening advice unchanged

Adults under 45 whose routine blood tests showed low levels of two liver enzymes were more likely to be diagnosed with colorectal cancer within a year of their first screening test, according to an Epic Research analysis released on September 9. An AST level below 14 U/L was associated with a 65 per cent higher likelihood of diagnosis, while an ALT level below 14 U/L was associated with a 68 per cent higher likelihood, compared with levels between 14 and 29 U/L.
The finding is an association identified through electronic health records and has not been published in a peer-reviewed journal. It does not show that low enzyme levels cause cancer. Doctors interviewed about the analysis said it does not change who should be screened.
The finding attracted attention because it runs counter to what many people might expect. High AST and ALT levels can indicate liver injury or inflammation, making the apparent link between low values and cancer noteworthy. Kersten Bartelt, a nurse and researcher at Epic Research, told CNN that "the direction was a little counterintuitive."
Why researchers are looking for early clues
Colorectal cancer rates among adults aged 20 to 49 have risen by roughly 3 per cent a year over the past decade, and the disease is now the leading cause of cancer death among Americans under 50, the Epic Research team said. The US Preventive Services Task Force lowered the recommended age to begin routine screening from 50 to 45 in 2021.
The trend has prompted doctors to look for warning signs in younger patients, who may not consider cancer when symptoms develop. Routine laboratory testing is appealing because many adults already undergo it.
Epic Research is part of Epic, the healthcare software company. The analysis used Cosmos, a dataset built with Epic health systems that contains more than 310 million patient records from all 50 US states, Canada, Lebanon and Saudi Arabia.
Inside the health-record analysis
The team studied 11,469 US adults aged 18 to 44 who had a first colorectal cancer screening between January 2017 and March 2025, as well as at least one AST or ALT result from the preceding three years. People with a previous cancer diagnosis, inflammatory bowel disease, Lynch syndrome, a family history of colon polyps or pregnancy were excluded.
Each patient diagnosed with colorectal cancer within a year of screening was matched with up to four patients who were not diagnosed. The analysis accounted for body weight and weight change, smoking, alcohol use disorder, diabetes, high blood pressure, fatty liver disease, malnutrition, and insulin and statin use. The published summary did not state how many cancer cases were included.
The pattern ran in both directions. An AST level of 30 or above was associated with a 22 per cent lower likelihood of diagnosis, while an ALT level of 30 or above was associated with a 29 per cent lower likelihood. Rising AST and ALT levels over three years were associated with 27 per cent and 26 per cent lower likelihoods, respectively, while falling levels showed no association. Triglycerides, HDL cholesterol and potassium showed no link.
What the analysis cannot explain
This was a case-control analysis of health records, and its main limitation is that it cannot establish causation. Low AST and ALT levels can reflect lower muscle mass, frailty or poor nutrition. Those underlying conditions, rather than the enzymes themselves, may explain the association. The researchers said adjustments for weight and malnutrition could not fully rule this out.
The study population also matters. Because routine screening is not generally recommended before 45, many patients in the analysis may have undergone a colonoscopy or another test because of symptoms or other risk factors. Bartelt told CNN that she suspects many had diagnostic rather than screening colonoscopies.
Independent experts urged caution. Dr Daniel Sussman of the University of Miami's Sylvester Comprehensive Cancer Center said the enzyme levels described as low "would generally be regarded clinically as normal values." He said the appropriate response was further investigation, rather than changing how clinicians interpret liver enzymes or determine who should be screened.
A larger UK study of more than 375,000 people previously associated higher AST and ALT levels, largely within the normal range, with a lower risk of colorectal cancer, lending some consistency to the signal. Dr Marc Fenster, a gastroenterologist at Episcopal Health Services in New York who was not involved in the research, described the new work as hypothesis-generating and said "it should not change how an individual patient is screened."
Symptoms and screening steps that still matter most
Adults at average risk should begin colorectal cancer screening at 45. People with a family history, certain personal health conditions or symptoms may need to start earlier and should discuss the timing with a doctor.
Symptoms deserve attention at any age. Rectal bleeding, unexplained weight loss, a lasting change in bowel habits and persistent abdominal pain should prompt a medical consultation rather than waiting until 45.
No one should try to raise their liver enzyme levels. Bartelt said nothing in the analysis suggests that changing them would alter cancer risk, and that the focus should be on overall health rather than a single laboratory result.
Cost can affect access. Most private health insurance plans in the US must cover recommended screening for average-risk adults aged 45 and older without cost-sharing, but a colonoscopy ordered because of symptoms may be billed as a diagnostic procedure. Patients can ask the medical practice in advance how the procedure will be coded.
The next step is validation. Caleb Cox, head of research at Epic, said a key question was how the findings would apply to a broader population. Outside experts called for peer-reviewed research before any change in clinical practice. For now, a low AST or ALT level on a routine blood test is not, on its own, a warning sign of cancer.
Key questions answered
What did the Epic Research analysis find?
Adults aged 18 to 44 with AST or ALT levels below 14 U/L before a first colorectal screening had 65 per cent and 68 per cent higher likelihoods, respectively, of being diagnosed with early-onset colorectal cancer.
Do low liver enzymes cause colorectal cancer?
There is no evidence that they do. The analysis found an association, and low enzyme levels may reflect other factors, such as low muscle mass or poor nutrition.
Was the analysis peer-reviewed?
No. It was released by Epic Research and has not been published in a peer-reviewed journal.
Should I be screened early if my AST or ALT level is low?
Doctors quoted about the analysis said no. Screening decisions should be based on age, family history and symptoms, not these values alone.
When should adults at average risk begin screening?
At 45, according to the US Preventive Services Task Force. People at higher risk may need to start earlier.
What symptoms should prompt a visit to the doctor?
Rectal bleeding, unexplained weight loss, lasting changes in bowel habits and persistent abdominal pain warrant medical evaluation at any age.
Should I try to raise my AST or ALT level?
No. Epic researchers said nothing suggests that changing these values would alter cancer risk, and outside doctors advised against trying to raise them.
Originally published on Medical Daily









