CALLY index shows no independent link to colorectal polyp risk

A newly reported observational study finds that the C-reactive protein–albumin–lymphocyte, or CALLY, index was not independently associated with colorectal polyp risk in 452 hospitalized gastroenterology patients, even after researchers adjusted for conventional risk factors and Traditional Chinese Medicine constitution. The finding contradicts the idea that CALLY may serve as a practical risk marker for the potentially precancerous lesions, at least in the clinical population studied. The authors stress that the result does not establish equivalence across all settings, particularly because the participants were hospital patients undergoing colonoscopy rather than an asymptomatic community screening cohort.

The study was designed retrospectively and cross-sectionally at a single Grade III Class A traditional Chinese medicine hospital in China. Between October and December 2025, investigators enrolled adults who completed colonoscopy and had compatible clinical records, blood-test results and colonoscopy findings. Patients were excluded if they had conditions that could substantially distort inflammatory or physiological measurements, including severe organ dysfunction, recent active infection, chronic inflammatory or autoimmune disease, recent major trauma or surgery, pregnancy or lactation, and current or previous malignancy. The final sample included 289 people with colorectal polyps and 163 without them, giving a polyp prevalence of 63.27 percent. Because the design was cross-sectional and confined to one hospital, the findings describe associations in this cohort rather than causes or prospective prediction.

Colorectal polyps were classified from colonoscopy findings and subsequent histopathology, with inflammatory polyps, colonic adenomas and other benign epithelial polyps counted as outcomes. CALLY was calculated from three fasting blood measurements: albumin in grams per liter multiplied by the absolute lymphocyte count in units of 10 to the ninth per liter, then divided by C-reactive protein in milligrams per liter. The index was considered both continuously and in four equal groups, from the lowest quartile, Q1, to the highest, Q4. Researchers constructed three logistic regression models: an unadjusted model, a model adjusting for gender, age, body mass index, diabetes, Traditional Chinese Medicine constitution, tongue color, tongue morphology and gastric polyps, and a further model that also included triglycerides and high-density lipoprotein cholesterol.

No statistically significant association between CALLY and polyps appeared in the progressively adjusted models. In the fully adjusted model, the odds ratios for colorectal polyps in Q2, Q3 and Q4, compared with Q1, were 0.81, 1.03 and 0.81, respectively; their 95 percent confidence intervals were 0.39 to 1.67, 0.49 to 2.14 and 0.41 to 1.61, and all corresponding P values exceeded 0.05. Polyp prevalence did not differ significantly across the four CALLY groups, with P equal to 0.76. The model’s area under the receiver operating characteristic curve was 0.85, and Hosmer–Lemeshow tests indicated good calibration, but these measures describe the model as a whole and do not indicate that CALLY contributed independently.

Sensitivity analyses produced the same central result. When CALLY was entered as a continuous variable, backward selection removed it from the final model; its estimated odds ratio was 1.000, with a 95 percent confidence interval of 1.000 to 1.001 and P equal to 0.22, while its addition to explanatory power was negligible. Natural splines with three degrees of freedom provided no evidence of a nonlinear or threshold relationship, with a likelihood ratio P value of 0.881. Results also remained unchanged when tongue signs or gastric polyps were removed from the adjusted model and when observations at the extreme 5th and 95th percentiles of CALLY were excluded. Interaction tests found no evidence that the association varied by gender, age, diabetes status, Traditional Chinese Medicine constitution or gastric polyps.

Several other variables were associated with colorectal polyps in the adjusted analyses. Male gender had an odds ratio of 0.56 in Model 2 and 0.57 in Model 3, indicating lower odds in this cohort rather than greater odds; the authors nevertheless listed sex among the factors consistently associated with risk. Advanced age was associated with higher odds, with an odds ratio of 1.04 per year in both models, meaning a 4 percent increase in odds for each additional year within this dataset. Diabetes was associated with substantially higher odds, with an odds ratio of 3.82 and a 95 percent confidence interval of 1.45 to 10.06 in Model 2, while gastric polyps were associated with an odds ratio of 2.11 and a 95 percent confidence interval of 1.26 to 3.53.

Traditional Chinese Medicine constitution, particularly the phlegm-dampness category, showed a large but statistically imprecise association with polyps. In Model 2, its odds ratio was 14.33, with a very wide 95 percent confidence interval of 3.60 to 57.05; in Model 3, the odds ratio was 15.50, with a confidence interval of 3.82 to 62.98. Only a small number of participants were classified with this constitution, making the estimate unstable. The investigators therefore treated the result as preliminary rather than evidence of a stable risk factor, and they called for independent validation in larger prospective cohorts. The constitution and tongue assessments were performed by trained practitioners who were blinded to laboratory results and colonoscopy findings, with a third senior practitioner resolving disagreements.

The researchers also tested whether triglycerides or high-density lipoprotein cholesterol could explain any relationship between CALLY and polyps through mediation analysis. Neither candidate pathway met the study’s statistical criterion. CALLY was not significantly associated with triglycerides or with high-density lipoprotein cholesterol, and neither lipid measure was significantly associated with polyps in the mediation models. The direct and total effects of CALLY were also non-significant, with all relevant P values above 0.05. Although CALLY correlated with triglycerides at r equal to −0.12 and with high-density lipoprotein cholesterol at r equal to 0.18, those correlations did not translate into detectable mediation in this cohort. The analysis was exploratory, and the sample was too small to exclude small or moderate indirect effects confidently.

The interpretation depends heavily on the population and the study’s statistical limits. A post-hoc calculation assumed an odds ratio of 1.5 for the highest versus lowest CALLY quartile, a two-sided alpha of 0.05, a sample of 452 and polyp prevalence of 63 percent; the resulting power was only 41.6 percent. Thus, the null findings mean that this study did not detect an independent association, not that every possible association has been ruled out. The cohort was clinically enriched: abdominal pain was more common among patients without polyps, at 34.36 percent versus 14.53 percent, and gastric polyps were also strongly associated with colorectal polyps. Differences in baseline risk and comorbidity structure may help explain why this inpatient study reached a different conclusion from an earlier health-screening cohort that associated higher CALLY scores with lower polyp risk, particularly among women.

Other limitations further constrain generalization. CALLY and lipid values were measured only once, leaving the analysis vulnerable to biological variation and measurement error. The retrospective dataset did not include detailed dietary habits, physical activity, family history of colorectal cancer or polyps, or anti-inflammatory medication use, so residual confounding cannot be excluded. Subgroup analyses were limited by small numbers of participants, and the findings cannot establish whether CALLY predicts future incident polyps because exposure and outcome were assessed in a cross-sectional hospital sample. On the evidence presented, routine CALLY testing for colorectal polyp risk had limited clinical utility in hospitalized gastroenterology patients, while larger multicenter prospective studies would be needed to determine whether the index has value in screening populations or underwrites any clinically useful lipid pathway.

Subject of Research: Association of the CALLY index with colorectal polyp risk in hospitalized gastroenterology patients

Article Title: CALLY is not associated with colorectal polyps risk: a systematic evaluation and mechanism exploration controlling for traditional factors and Traditional Chinese Medicine constitution

Article References: Zhang, K., Wu, X., Lin, F., Chen, B., & Han, Y. (2026). CALLY is not associated with colorectal polyps risk: a systematic evaluation and mechanism exploration controlling for traditional factors and Traditional Chinese Medicine constitution. Frontiers in Public Health, 14, Article 1953202. https://doi.org/10.3389/fpubh.2026.1953202

Image Credits: AI Generated

DOI: 10.3389/fpubh.2026.1953202

Keywords: CALLY index, colorectal polyps, inflammation, risk assessment, gastric polyps, diabetes, Traditional Chinese Medicine, lipid metabolism, cross-sectional study, CALLY, associated, colorectal