First on CNN: Routine blood testing may hold hidden clues to colorectal cancer before age 45

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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.

Why young people are dying from colorectal cancer

“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.

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.

How to lower your risk of colorectal cancer

Get screened. Almost all colorectal cancers begin as precancerous polyps that can be identified and removed via colonoscopy.

Keep a healthy body weight.

Stay physically active.

Limit alcohol consumption.

Limit red meat and processed foods and eat plenty of fiber, such as whole grains, fruits and vegetables.

“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.”

Colorectal cancer now leading cause of cancer deaths in Americans under 50

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.

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.

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As more young people get screened, more colon cancer is being found early. Here’s how to lower your risk

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% 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% higher likelihood than their peers.

In contrast, higher AST levels – 30 or above – were associated with a 22% lower likelihood of being diagnosed with colorectal cancer, and ALT levels of 30 or above were associated with a 29% 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% lower likelihood of colorectal cancer and a rising ALT with a 26% 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.”

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.

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More young people are getting early-onset colorectal cancer. 5 things to know

“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.”

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First-of-its-kind study may help explain why colorectal cancers are rising sharply in young people

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.”

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最新研究表明，在例行体检抽血时，一些检测指标可能蕴含着意想不到的线索，可以预测你在年轻时患上结直肠癌的可能性。

医疗保健软件公司 Epic 旗下的 Epic Research 周三发布的一项分析显示，45 岁以下的成年人如果体内两种肝酶（天冬氨酸转氨酶 (AST) 和丙氨酸转氨酶 (ALT)）水平较低，则比同龄人更容易被诊断出患有早发性结直肠癌。

“这个结果有点违反直觉。临床上，我们倾向于关注肝酶水平，所以发现 AST 和 ALT 水平低与早发性结直肠癌的发生率较高相关，这一点就显得尤为突出，”参与这项新分析的 Epic Research 临床医生兼研究员 Kersten Bartelt 说。

但医生表示，AST 或 ALT 值较低的年轻成年人不必惊慌，结肠癌筛查建议也没有改变。

这项新研究强调了低水平胆固醇与癌症之间的关联，但这并不意味着低水平胆固醇会导致癌症，也不意味着人们应该仅仅因为胆固醇水平低就急于进行早期结肠镜检查。相反，这些尚未在同行评审期刊上发表的研究结果，提示我们应深入研究这一领域，以更好地了解年轻人结直肠癌发病率上升的潜在因素。

为什么年轻人会死于结直肠癌

“我们的研究揭示了这种关联，但并非旨在揭示其原因，”巴特尔特说。“临床上，AST 和 ALT 水平低可能反映出肌肉量减少、身体虚弱或营养不良等问题。我们希望这项研究能促使其他研究者对此进行深入探讨。”

这些新发现令人瞩目，因为AST和ALT水平升高有时是肝脏不健康的征兆，某些疾病，例如肝病或感染，都会导致这些指标升高。这些指标通常包含在常规血液检查中，因为肝酶升高可能是肝损伤、炎症或疾病的早期预警信号，甚至在症状出现之前就能发挥作用。

巴特尔特说：“我们不建议任何人尝试提高AST和ALT的数值。”

“我们的研究没有任何迹象表明改变这些指标会改变一个人的癌症风险，”她说。“这些指标可能反映的是肌肉和营养状况等潜在的生理因素，因此重点应该放在与临床医生合作的整体健康上，而不是仅仅关注某个实验室指标的变化。”

除了检测AST和ALT水平外，Bartelt及其同事还检测了甘油三酯、胆固醇和钾的水平。他们发现，其他常规实验室检查结果均与早发性结直肠癌无关。

结直肠癌在年轻人中发病率不断上升的原因一直是医学界关注的焦点。在美国，结直肠癌已经超过其他类型的癌症，成为50岁以下人群癌症死亡的首要原因。

“每当人们关注结肠癌，特别是早发性结肠癌时，我们都需要弄清楚原因。早发性结肠癌的发病率确实有所上升，如果能找到一些标志物，帮助我们找到合适的筛查对象，那就太好了，”纽约圣公会医疗服务中心的胃肠病学家马克·芬斯特博士说道，他并未参与这项新研究。

如何降低患结直肠癌的风险

接受筛查。几乎所有的结直肠癌都是从癌前息肉开始的，这些息肉可以通过结肠镜检查发现并切除。

保持健康的体重。

保持身体活跃。

限制饮酒量。

限制红肉和加工食品的摄入，多吃富含纤维的食物，例如全谷物、水果和蔬菜。

“关于早发性结直肠癌的讨论主要集中在家族史和遗传因素、肥胖和代谢健康、饮食、缺乏运动、肠道菌群、抗生素暴露以及年轻患者症状识别延迟等问题上。然而，这些因素都无法完全解释病例增加的原因，”芬斯特说。“这项研究或许能拓展讨论范围，因为它表明常规收集的代谢和营养指标可能包含有用的线索。”

芬斯特补充说，虽然这项研究指出了一个“信号”并且“提出了假设”，但它并没有确定低 AST 或 ALT 是早发性结直肠癌的风险因素。

“这项研究应该鼓励进一步研究，但不应该改变对单个患者的筛查方式，”他说。

“我不想让人们觉得，如果AST或ALT值低，就意味着他们要患结肠癌，或者需要改变什么生活方式，”他说。“如果你没有家族病史，没有任何症状，身体健康，没有体重下降，也没有直肠出血，那么这项研究并不会改变我的做法。”

结直肠癌现已成为美国50岁以下人群癌症死亡的首要原因。

在美国，临床指南建议所有平均风险人群从45岁开始接受结直肠癌筛查。风险较高的人群——例如由于自身健康史、家族史或症状等因素——可能需要更早开始筛查。血液检测目前也是一种结直肠癌筛查方法。

今年 5 月，美国癌症协会首次将血液筛查测试添加到其推荐的筛查选择列表中，适用于 45 岁及以上、患结直肠癌风险中等、尚未完成或拒绝视觉检查和粪便检查的成年人。

该组织推荐的血液筛查测试是 Shield 测试，该测试不属于常规血液检查项目。

结肠镜检查仍然被认为是筛查的金标准，血液检测并非患者的首选。此外，Shield血液检测结果呈阳性并非最终诊断；患者必须及时进行结肠镜检查。

芬斯特表示，血液检测“绝不能以任何方式取代结肠镜检查”。

为了揭示哪些常规实验室检查结果可能与早发性结直肠癌相关，巴特尔特及其同事分析了美国各地11000多名18至44岁人群的健康数据。每位成年人都在2017年至2025年间接受了首次结直肠癌筛查，并且在筛查前三年内至少接受过一次AST或ALT检测。

但由于结直肠癌常规筛查建议45岁以后才开始，因此尚不清楚纳入分析的患者为何接受了结肠镜检查或其他筛查。这可能是由于家族史、症状或其他高危因素所致。

巴特尔特说：“我怀疑这些患者是因为出现了某种症状才来就诊的，他们接受的是诊断性结肠镜检查，而不是筛查性结肠镜检查。”

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随着越来越多的年轻人接受筛查，结肠癌的早期发现率也越来越高。以下是如何降低患病风险的方法。

研究人员分析了在筛查后一年内被诊断出患有结直肠癌的成年人的数据，并将其与未被诊断出患有该疾病的成年人的数据进行了比较。

分析显示，AST 水平低于每升血液 14 单位的成年人，与 AST 水平在 14 至 29 单位之间的同龄人相比，患早发性结直肠癌的可能性高出 65%。同样，ALT 水平低于 14 的成年人，患早发性结直肠癌的可能性也比同龄人高出 68%。

相比之下，AST 水平较高（30 或以上）与患结直肠癌的可能性降低 22% 相关，ALT 水平较高（30 或以上）与患结直肠癌的可能性降低 29% 相关。

研究人员表示，他们使用 14 到 29 的水平作为比较值，因为这些水平处于新分析中观察到的水平范围的中间值。

巴特尔特说：“从临床角度来看，这些酶因人而异，并且会随着活动水平、肌肉量、疾病或药物等因素而随时间发生变化。”

研究人员还密切关注了 AST 和 ALT 水平随时间的变化，特别是成年人接受癌症筛查前三年内升高的水平。

数据显示，与AST水平稳定的成年人相比，AST升高与结直肠癌风险降低27%相关，ALT升高与结直肠癌风险降低26%相关。AST或ALT水平降低与结直肠癌均无显著相关性。

不过，在医学界，AST 或 ALT 的“正常”水平的定义可能有所不同。

迈阿密大学健康系统西尔维斯特综合癌症中心胃肠病高危预防诊所负责人丹尼尔·萨斯曼博士在一封电子邮件中表示，虽然每个诊断实验室可能都有自己测量“正常”AST 和 ALT 水平的参考范围，但“本研究中描述为‘低’的 AST 和 ALT 水平通常在临床上被认为是正常值”。

“这让我格外谨慎，不敢断言这些实验室结果代表异常或具有实际意义的结直肠癌风险标志物，”苏斯曼写道，他并未参与这项新研究。“意外发现固然可以引出有价值的研究问题，但也需要格外谨慎的验证。”

另一项发表在《国际癌症杂志》上的研究也发现，AST 和 ALT 水平较高（但仍在正常范围内）与结直肠癌风险降低相关。该研究基于 2006 年至 2010 年间英国超过 37.5 万人的血液样本。

那项研究与这项新分析的侧重点不同：它评估了肝酶水平与结直肠癌长期风险之间的关联，而这项新分析则考察了常规血液检查能否发现未确诊的早发性结直肠癌。但尽管两篇论文的研究方向不同，它们都显示ALT和AST水平与结直肠癌（CRC）之间存在负相关关系。

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越来越多的年轻人罹患早发性结直肠癌。以下5点你需要了解。

“这些发现，加上我们之前关于总体 CRC 的研究结果，凸显了进一步了解肝功能变化在 CRC 中的病因和预测作用的必要性，”哈佛大学陈曾熙公共卫生学院副教授宋明阳（音译）在一封电子邮件中表示。宋明阳是之前研究的作者之一，但没有参与这项新的分析。

“在我们的研究中，参与者总体健康状况良好，因此他们的AST/ALT水平大多在正常范围内。对于这些人来说，较低的AST/ALT水平可能反映出肝脏功能和代谢能力的下降，这可能表明他们更容易受到毒素和致癌物的侵害，”宋写道。“这种易感性可能转化为更高的结直肠癌风险。”

但他补充说，不应仅凭AST或ALT水平就提出临床建议。巴特尔特也认同，AST或ALT结果偏低本身并不值得担忧。

巴特尔特表示：“还需要进一步研究来确定低AST或ALT值应如何纳入早期筛查建议。我的建议是，及时了解推荐的筛查项目——对于一般风险的成年人，应在45岁时进行常规筛查；对于有症状、家族史或其他风险因素的人，则应更早进行筛查——并与您的医疗团队讨论您的具体情况。”

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这项开创性的研究或许有助于解释为什么年轻人中结直肠癌的发病率急剧上升

萨斯曼补充说，他不建议任何人尝试提高他们的 AST 或 ALT 水平，而且这项新研究并没有改变有关结直肠癌筛查的临床指南。

总的来说，他不建议仅根据 AST 或 ALT 值对 45 岁以下的成年人进行筛查。

萨斯曼写道：“这项分析似乎只是探索性的。我认为，目前更恰当的做法是进行进一步调查，而不是改变临床医生对正常肝酶水平的解读方式，或者改变我们决定哪些人应该接受结直肠癌筛查的方式。”

Epic 的研究主管 Caleb Cox 负责监督这项新分析背后的团队，他表示，新发现提出的后续研究问题之一是：“这如何推广到更广泛的人群？”

考克斯表示，年轻人群中结直肠癌病例的增加是“一个新兴领域，目前还没有太多答案”。“我们认为这些低水平的AST和ALT并非直接原因。它们或许可以提示，可能存在某种因素导致AST和ALT水平降低，而这或许也是年轻人群中结直肠癌发病率上升的根本驱动因素。”