To the Editor,
Serum CA72-4 is one of the most valuable markers for auxiliary diagnosis, monitoring and curative effect assessment of gastric cancer , , , , . However, its elevation was observed in some other tumors including gastrointestinal, pancreatic, ovarian and endometrium malignancies , , , . Therefore, CA72-4 has been widely used in clinical practice. However, it has been reported that some food or health-promotion products such as mushroom and ganoderma lucidum spore powder can cause abnormal elevation of serum CA72-4 in healthy individuals or patients with tumors , , . Till now, there has been no report about the effect of drugs on serum CA72-4 level. We present the case of a patient with abnormal elevation of serum CA72-4 level due to taking colchicine. Moreover, we also explore the general effect of colchicine on serum CA72-4 in another nine patients who received colchicine treatment.
On April 9th, 2013, a 51-year-old man came to our hospital for a routine physical examination. Abdominal ultrasonography showed a mild fatty liver without other abnormalities. Laboratory results showed slightly elevated serum triglycerides (2.28 mmol/L; upper normal limit 1.7 mmol/L) and significantly increased CA72-4 (159.4 U/mL; upper normal limit 6.9 U/mL). Other laboratory results including serum cholesterol, glucose, creatine kinase-MB (CK-MB), cardiac troponin, α1-fetoprotein (AFP), carcinoembryonic antigen (CEA), CA19-9, CYFRA21-1, neuron specific enolase (NSE), liver and renal function tests, etc., were within normal ranges. It needs to be explained that the determination for all the tumor markers mentioned above was required by the patient. Of note, all of the tumor markers were measured by electrochemiluminescence immunoassays using the Modular E601 automated analyzer (Roche, Basel, Switzerland). The analyzer was routinely maintained according to the manufacturer’s instructions. Dedicated reagents and standard methodologies were used. Internal quality controls (IQC) were performed by the Westgard alert rules during the entire period of the study. Accordingly, the results should be reliable. The patient who had no tumor history and no family history of tumor felt very nervous and consulted a doctor in Medical Examination Center. Therefore, the gastroscopy, enteroscopy and body computerized tomography scan were performed to exclude the possibility of gastrointestinal, liver, gallbladder and pancreas cancers, but all of the results were negative. Upon further communication with the patient, it was discovered that colchicine had been taken orally at a dose of 1 mg three times daily by him for treatment of gouty arthritis for 1 week. No other medications were used at the same time. As the patient had achieved remission, considering the effect of colchicine, he was advised to discontinue taking colchicine. One week later, he returned to our hospital to recheck his serum CA72-4. It had fallen significantly (10.45 U/mL), although it was still over the upper normal limit. However, his serum uric acid level was 540 mmol/L. On April 22, 2013, the gout arthritis flared up again. The patient continued taking colchicine at home. On May 30, 2013, he returned to our hospital. The results showed 575 mmol/L for serum UA and >300 U/mL for CA72-4. On further communication with the patient, colchicine was replaced by etoricoxib (120 mg qd, oral) for treatment of his gout. Four days later, CA72-4 was reduced to 73.59 U/mL, while UA was 573 mmol/L. Serum CA 72-4 and UA were, respectively, 17.19 U/mL and 583 mmol/L 2 weeks later, and 2.31 U/mL and 553 mmol/L 6 weeks later. Over the next 3 years his serum CA72-4 remained stable (~ 2.5 U/mL).
To determine if colchicine can interfere with the CA72-4 assay, we collected additional six serum samples. Each sample was divided into four parts. One was used as a control, and the other three were incubated with saturated colchicine for 1 h, 2 h and 3 h, respectively. The results showed no significant difference for serum CA72-4 level between various parts (see Table 1).
In addition, we included another nine gout patients who received only colchicine treatment. The study was approved by the research Ethics Committee of our institution, and signed informed consents were obtained from all the patients. The blood was drawn from these patients before treatment, 5 days after colchicine treatment and 3 weeks after discontinuing treatment. Serum CA72-4 was measured. The results showed that serum CA72-4 levels were within normal range in all the patients before treatment, but significantly increased 5 days after colchicine treatment and reduced within normal range again 3 weeks after discontinuing treatment (see Table 2).
As is known colchicine has anti-inflammatory and anti-proliferative effects via perturbing microtubule spindle formation, resulting in cell cycle arrest and eventual cell death, impairing neutrophil chemotaxis, inhibiting cytokine production . As an alkaloid agent, colchicine has been widely used for gout treatment for at least several hundred years . Besides being used for gout, colchicine has also been used in many other diseases including familial Mediterranean fever, pericarditis, coronary artery disease and other inflammatory and fibrotic conditions . It has been approved by the US Food and Drug Administration for treatment of acute gout and familial Mediterranean fever and for prophylaxis against gouty arthritis . Furthermore, it has been found to exhibit an anticancer effect . However, to date it has been remained unknown whether colchicine can influence serum tumor marker levels.
To the best of our knowledge, this is the first case report about abnormal elevation of serum CA72-4 level which could be caused by colchicine. In our case, the patient only took colchicine for treatment of gout without taking any other drugs. Moreover, this case report indicates that an abnormal CA72-4 level is not associated with high serum UA level as serum CA72-4 was reduced to normal levels yet with high serum UA in this patient after cessation of colchicine medication. Therefore, we can be sure to state that it is colchicine that causes abnormal elevation of serum CA72-4. Furthermore, abnormal elevation of serum CA72-4 caused by colchicine was also found in another nine patients, suggesting that this could be the general effect of colchicines. However, we also verified that colchicine may not directly interfere with the CA72-4 assay. Strangely, other tumor markers including AFP, CEA, CA19-9, PSA, CA72-4, CYFRA21-1 and NSE are not influenced by colchicine. The detailed mechanisms by which it causes the increase of CA72-4 in vivo remain to be clarified by further clinical and basic studies.
Up to date, as is known, mushroom and ganoderma lucidum spore powder can cause abnormal elevation of serum CA72-4. This case report alerts clinicians to an additional fact, that abnormal elevation of serum CA72-4 dose also occurs in patients receiving colchicine medication. This should be explained to the patient after excluding various related diseases.
Liang Y, Wang W, Fang C, Raj SS, Hu WM, Li QW, Zhou ZW. Clinical significance and diagnostic value of serum CEA, CA19-9 and CA72-4 in patients with gastric cancer. Oncotarget 2016;7:49565–73. Web of ScienceCrossrefPubMedGoogle Scholar
Shimada H, Noie T, Ohashi M, Oba K, Takahashi Y. Clinical significance of serum tumor markers for gastric cancer: a systematic review of literature by the Task Force of the Japanese Gastric Cancer Association. Gastric Cancer 2014;17:26–33. CrossrefWeb of ScienceGoogle Scholar
Ychou M, Duffour J, Kramar A, Gourgou S, Grenier J. Clinical significance and prognostic value of CA72-4 compared with CEA and CA19-9 in patients with gastric cancer. Dis Markers 2000;16:105–10. PubMedCrossrefGoogle Scholar
Byström P, Berglund A, Nygren P, Wernroth L, Johansson B, Larsson A, et al. An explorative study on the clinical utility of baseline and serial serum tumour marker measurements in advanced upper gastrointestinal cancer. Oncol Rep 2010;24:1645–52. PubMedWeb of ScienceGoogle Scholar
Terry KL, Schock H, Fortner RT, Hüsing A, Fichorova RN, Yamamoto HS, et al. A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC Cohort. Clin Cancer Res 2016;22:4664–75. Web of ScienceCrossrefPubMedGoogle Scholar
Anastasi E, Manganaro L, Granato T, Benedetti Panici P, Frati L, Porpora MG. Is CA72-4 a useful biomarker in differential diagnosis between ovarian endometrioma and epithelial ovarian cancer? Dis Markers 2013;35:331–5. PubMedCrossrefWeb of ScienceGoogle Scholar
Li ZY, Sun LH. Abnormal elevation of serum CA72-4 by mushroom: a case report. Chin J Lab Med 2011;34:180–1. Google Scholar
Yan B, Meng X, Shi J, Qin Z, Wei P, Lao L. Ganoderma lucidum spore induced CA72-4 elevation in gastrointestinal cancer: a five-case report. Integr Cancer Ther 2014;13:161–6. CrossrefPubMedWeb of ScienceGoogle Scholar
Kuo MC, Chang SJ, Hsieh MC. Colchicine significantly reduces incident cancer in gout male patients: a 12-year cohort study. Medicine (Baltimore) 2015;94:e1570. Web of SciencePubMedCrossrefGoogle Scholar
About the article
Published Online: 2017-07-05
Published in Print: 2017-11-27
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This study was supported by the grant from the National Natural Science Foundation Council (81671594).
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.