Association between geriatric nutritional risk index and colorectal adenoma risk in an asymptomatic screening population

Abstract

BACKGROUND

Gastrointestinal cancers pose a major global health burden. Nutritional status has also been associated with cancer risk. The geriatric nutritional risk index (GNRI) is a validated tool for assessing nutritional risk. This study investigated the utility of the GNRI in predicting gastrointestinal tumor risk in an asymptomatic population.

AIM

To investigate the association between GNRI and incident gastrointestinal neoplasia in an asymptomatic population undergoing annual health examinations.

METHODS

We retrospectively enrolled 175 consecutive subjects who visited our hospital in January 2020 to December 2023, voluntarily completed a colonoscopy, and had complete baseline data. Demographics, anthropometrics, routine biochemistry, tumor markers, and endoscopic histopathology were collected. GNRI was calculated, and participants were classified as well-nourished, at-risk, or malnourished. Univariable and multivariable logistic regression were used to analyze the relationship between GNRI and colorectal neoplasia. Receiver operating characteristic analysis was performed to assess GNRI’s discriminative ability for colorectal adenoma.

RESULTS

According to the GNRI, 86 (49.1%) participants were well-nourished, 62 (35.4%) were at risk, and 27 (15.4%) were malnourished. Polyp detection rates were 38.4%, 56.5%, and 70.4%, and adenoma detection rates were 22.1%, 45.2%, and 58.3% (P < 0.05). Malnourished individuals had the highest proportion of advanced adenomas (P < 0.05). Multivariable analysis identified age [odds ratio (OR) = 1.037; 95% confidence interval (CI): 1.003-1.072], triglycerides (OR = 1.468; 95%CI: 1.036-2.080) and carcinoembryonic antigen (OR = 1.254; 95%CI: 1.053-1.493) as independent risk factors, whereas GNRI (OR = 0.692; 95%CI: 0.589-0.813), albumin (OR = 0.815; 95%CI: 0.722-0.920) and body mass index (OR = 0.889; 95%CI: 0.803-0.984) were independent protective factors (all P < 0.05). The area under the curve (AUC) of GNRI for predicting adenoma was 0.874 (95%CI: 0.77-0.92), outperforming albumin alone (AUC = 0.743) and body mass index alone (AUC = 0.656). At the optimal cutoff of 95.6, GNRI yielded sensitivity and specificity of 84.5% and 81.2%, respectively.

CONCLUSION

GNRI is a powerful and reliable predictor of colorectal premalignant lesions in health-screening settings and effectively stratifies adenoma risk across nutritional states. GNRI has potential as an adjunctive risk-stratification tool.

Key Words: Geriatric nutritional risk index; Colorectal adenoma; Nutritional assessment; Risk of occurrence; Predictive performance

Core Tip: This health screening-based cohort study demonstrates that the geriatric nutritional risk index (GNRI) effectively stratifies the risk of colorectal premalignant lesions in asymptomatic adults. With an optimal cutoff of 95.6, the GNRI predicted adenoma occurrence with high accuracy (area under the curve = 0.874), outperforming individual measurements of serum albumin or body mass index. Lower GNRI values were independently associated with increased adenoma detection rates and advanced histology, supporting the use of the GNRI as a simple, noninvasive tool for prioritizing high-risk individuals for gastrointestinal tumor surveillance.

INTRODUCTION

Gastrointestinal malignancies remain a major global public health burden, ranking among the leading causes of morbidity and mortality, and imposing substantial economic and caregiving costs on society and families[1,2]. Although colonoscopy is considered the gold standard for detecting colorectal neoplasia, its invasive nature, high cost, and limited capacity render it less suitable for mass screening[3,4]. Consequently, identifying a simple, non-invasive, and cost-effective predictor is of considerable clinical and population health importance.

Over the past decade, accumulating evidence has linked nutritional status to the initiation and progression of various chronic diseases, including cancer[5,6]. Nutritional imbalance may promote a tumor-permissive microenvironment by compromising immune surveillance, amplifying chronic low-grade inflammation, inducing mitochondrial dysfunction, increasing oxidative stress, and altering gut microbial ecology[7,8].

The geriatric nutritional risk index (GNRI) - an objective, quantitative, and readily reproducible metric that integrates serum protein levels and body weight changes - was originally developed to predict clinical outcomes in older adults. More recently, its utility has been extended to risk stratification for chronic heart failure, renal insufficiency, and selected malignancies[9,10].

Building on these observations, we conducted a retrospective cohort study to elucidate the relationship between GNRI and incident gastrointestinal neoplasia to provide novel evidence for the early detection and prevention of digestive tract tumors.

MATERIALS AND METHODS

Study population

We retrospectively enrolled 175 consecutive patients who visited the Department of General Practice and Health Management of our hospital for annual health screening between January 2020 and December 2023 and voluntarily underwent complete colonoscopy. The study protocol was approved by our Institutional Medical Ethics Committee. Colonoscopy was conducted as part of an elective health screening program rather than a population-based mandatory screening initiative.

Inclusion criteria: (1) Age ≥ 40 years; (2) Complete and detailed data on anthropometry, laboratory tests, and colonoscopic findings; and (3) Signed informed consent.

Exclusion criteria: (1) Previous history of malignancy; (2) Major surgery, severe trauma, or acute infection within 12 months before enrolment; (3) Severe hepatic or renal insufficiency, decompensated heart failure, inflammatory bowel disease, or other chronic wasting disorders that could substantially affect nutritional status; (4) Pregnancy or lactation; and (5) Poor colonoscopic quality precluding adequate mucosal visualization.

Data collection

All variables were retrieved from the institutional electronic medical-record system and comprised: (1) Baseline demographics and lifestyle: Age, sex, smoking history (continuous or cumulative smoking ≥ 6 months), alcohol consumption (average ethanol intake > 30 g/day for ≥ 1 year); (2) Anthropometrics: Height and weight were measured using calibrated instruments, and body mass index (BMI) was calculated as weight (kg)/height² (m²); and (3) Laboratory assays: After an overnight fast of 8-12 hours, morning venous blood was drawn for serum albumin, total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol), fasting plasma glucose, glycated hemoglobin, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9 (19-9), CA72-4 and uric acid. Helicobacter pylori status was determined using western blotting for serum cytotoxin-associated gene antigen-immunoglobulin G and urease B subunit-immunoglobulin G positivity for either or both defined Helicobacter pylori-positive.

Colonoscopy and histopathology

All examinations were performed by experienced endoscopists (> 1000 lifetime procedures). The number, size, morphology (Paris classification), and location of each polyp were recorded. Resected specimens were fixed, paraffin-embedded, sectioned at 4 μm, and stained with hematoxylin-eosin. Two gastrointestinal pathologists independently established the final diagnosis, and any discrepancies were resolved through joint review. Lesions were classified as tubular, villous, or tubulovillous adenomas; hyperplastic polyps; inflammatory polyps; or other lesion types. Advanced adenoma was defined as ≥ 10 mm in diameter, high-grade intraepithelial neoplasia, or > 25% villous component.

GNRI calculation and grouping

GNRI = [1.489 × albumin (g/L)] + [41.7 × (actual weight/ideal weight]), where ideal weight (kg) = height² (m²) × 22. Participants were categorized as: (1) Well-nourished: GNRI ≥ 98; (2) At nutritional risk: 92 ≤ GNRI < 98; and (3) Malnourished: GNRI < 92.

Statistical analysis

All analyses were performed using SPSS 26.0. Normally distributed continuous variables are presented as mean ± SD; non-normally distributed variables as median (inter-quartile range). Between-group comparisons were conducted using one-way analysis of variance or Kruskal-Wallis H test, as appropriate. Categorical data are expressed as n (%) and compared by χ² or Fisher’s exact test. Pearson’s correlation was used to evaluate associations between GNRI and continuous covariates. Variables significant in univariable analysis (P < 0.10) were entered into a multivariable logistic regression with forward stepwise selection (likelihood-ratio criterion) to identify independent predictors of colorectal adenoma. Receiver operating characteristic (ROC) curves were constructed, and the area under the curve (AUC) was calculated to quantify the discriminatory performance of GNRI. Statistical significance was set at P < 0.05.

RESULTS

Baseline characteristics across GNRI categories

Among the 175 enrolled participants, 86 (49.1%) were classified as well-nourished (GNRI ≥ 98), 62 (35.4%) at nutritional risk (92 ≤ GNRI < 98), and 27 (15.4%) malnourished (GNRI < 92). Across these groups, we observed significant differences in age, BMI, serum albumin, selected lipid parameters, and tumor markers (all P < 0.05). Participants in the malnourished group were older; had lower BMI, albumin, and high-density lipoprotein cholesterol levels; and displayed higher TGs, fasting glucose, CEA, and CA19-9 concentrations (Table 1).

Table 1 Comparison of baseline characteristics and clinical parameters among subjects in different geriatric nutritional risk index groups, n (%).

Variable	Well-nourished (n = 86)	At-risk (n = 62)	Malnourished (n = 27)	Statistic	P value
Age (year), mean ± SD	59.6 ± 10.1	64.3 ± 8.9	67.8 ± 7.2	F = 9.847	< 0.001
Male sex	46 (53.5)	36 (58.1)	16 (59.3)	χ2 = 0.493	0.781
Smoking	22 (25.6)	18 (29.0)	8 (29.6)	χ2 = 0.324	0.852
Alcohol use	19 (22.1)	15 (24.2)	7 (25.9)	χ2 = 0.210	0.901
BMI (kg/m2), mean ± SD	25.7 ± 3.1	22.5 ± 2.6	20.1 ± 2.1	F = 48.632	< 0.001
Albumin (g/L), mean ± SD	42.5 ± 2.9	38.1 ± 2.3	34.8 ± 2.7	F = 125.301	< 0.001
Total cholesterol (mmol/L), mean ± SD	4.85 ± 0.91	4.65 ± 0.87	4.48 ± 0.95	F = 3.885	0.055
Triglycerides (mmol/L), mean ± SD	1.65 ± 0.78	1.82 ± 0.85	1.91 ± 0.92	F = 3.362	0.038
HDL-C (mmol/L), mean ± SD	1.35 ± 0.31	1.21 ± 0.28	1.08 ± 0.25	F = 12.954	< 0.001
LDL-C (mmol/L), mean ± SD	2.89 ± 0.71	2.78 ± 0.68	2.65 ± 0.74	F = 1.405	0.251
Fasting glucose (mmol/L), mean ± SD	5.21 ± 0.89	5.58 ± 1.12	5.87 ± 1.24	F = 6.098	0.003
CEA (ng/mL), mean ± SD	2.12 ± 1.54	3.01 ± 1.89	3.98 ± 2.45	F = 12.335	< 0.001
CA19-9 (U/mL), mean ± SD	12.5 ± 9.8	16.8 ± 12.3	21.4 ± 15.1	F = 8.214	< 0.001
H. pylori positive	38 (44.2)	32 (51.6)	16 (59.3)	χ2 = 2.271	0.321

BMI: Body mass index; GNRI: Geriatric nutritional risk index; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9; H. pylori: Helicobacter pylori; F: One-way analysis of variance statistic.

GNRI and colorectal end-points

Detection rates for any polyp increased progressively across GNRI categories: 38.4% (well-nourished), 56.5% (at-risk), and 70.4% (malnourished) (P < 0.05). Corresponding adenoma detection rates were 22.1%, 45.2%, and 58.3%, respectively (P < 0.05). Subtype analysis revealed the highest proportion of advanced adenomas in the malnourished stratum (P < 0.05) (Figure 1).

Figure 1 Comparison of colorectal polyp and adenoma detection rates across different geriatric nutritional risk index groups. GNRI: Geriatric nutritional risk index.

Independent determinants of colorectal adenoma

Multivariable logistic regression (forward likelihood-ratio) identified age [odds ratio (OR) = 1.037; 95% confidence interval (CI): 1.003-1.072], TGs (OR = 1.468; 95%CI: 1.036-2.080) and CEA (OR = 1.254; 95%CI: 1.053-1.493) as independent risk factors, while GNRI (OR = 0.692; 95%CI: 0.589-0.813), albumin (OR = 0.815; 95%CI: 0.722-0.920) and BMI (OR = 0.889; 95%CI: 0.803-0.984) were inversely associated with colorectal adenoma risk (all P < 0.05) (Table 2).

Table 2 Multivariate logistic regression analysis of colorectal adenoma risk factors.

Variable (per 1-unit increase)	β	SE	Wald χ2	VIF	P value	Adjusted OR (95%CI)
Age (per year)	0.036	0.017	4.48	1.28	0.034	1.037 (1.003-1.072)
BMI (per kg/m2)	-0.118	0.052	5.15	1.45	0.023	0.889 (0.803-0.984)
Albumin (per g/L)	-0.205	0.062	10.93	1.67	0.001	0.815 (0.722-0.920)
HDL-C (per mmol/L)	-0.892	0.478	3.48	1.38	0.062	0.410 (0.161-1.045)
Triglycerides (per mmol/L)	0.384	0.178	4.66	1.39	0.031	1.468 (1.036-2.080)
Fasting glucose (per mmol/L)	0.198	0.121	2.68	1.45	0.102	1.219 (0.962-1.545)
CEA (per ng/mL)	0.226	0.089	6.45	1.23	0.011	1.254 (1.053-1.493)
CA19-9 (per U/mL)	0.025	0.014	3.19	1.31	0.074	1.025 (0.998-1.054)
GNRI (per unit)	-0.368	0.082	20.12	1.89	< 0.001	0.692 (0.589-0.813)

BMI: Body mass index; HDL-C: High-density lipoprotein cholesterol; CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9; GNRI: Geriatric nutritional risk index; SE: Standard error; VIF: Variance inflation factor; OR: Odds ratio; CI: Confidence interval.

Discriminative performance of the GNRI

ROC analysis yielded an AUC of 0.874 (95%CI: 0.77-0.92) for GNRI in predicting colorectal adenoma, outperforming albumin alone (AUC = 0.743) and BMI alone (AUC = 0.656). At the optimal cutoff value of 95.6, GNRI achieved 84.5% sensitivity and 81.2% specificity (Figure 2).

Figure 2 Receiver operating characteristic curve comparison of geriatric nutritional risk index, albumin, and body mass index in predicting colorectal adenomas. GNRI: Geriatric nutritional risk index; AUC: Area under the curve; BMI: Body mass index.

DISCUSSION

Accelerated population aging and unfavorable lifestyle transitions have driven a sustained increase in the incidence of gastrointestinal malignancies in China[11,12]. Colorectal cancer is currently the third most common cancer nationwide, and its stepwise progression from precursor adenomas is well established[13,14]. Early detection and removal of adenomatous polyps, therefore, constitute a key public health strategy for reducing the burden of colorectal cancer[15,16]. This study is the first to examine whether GNRI, an objective surrogate of nutritional status, can be repurposed as a noninvasive predictor of colorectal adenoma in an apparently healthy screening cohort.

We found a clear nutritional gradient: Polyp detection rates increased from 38.4% in well-nourished participants to 56.5% in the at-risk group and 70.4% in the malnourished group; corresponding adenoma detection rates were 22.1%, 45.2%, and 58.3%, respectively (P < 0.05). These findings imply that lower GNRI values may reflect underlying systemic vulnerability or subclinical disease burden rather than directly causing adenoma formation. Plausible biological pathways include: (1) Impaired gut barrier integrity and diminished mucosal immunity, which facilitate carcinogen entry and chronic inflammation[17,18]; and (2) Insufficient micronutrients and amino acids required for DNA repair and epithelial homeostasis, leading to dysregulated cellular proliferation[19,20]. Similar mechanisms have been proposed in chronic obstructive pulmonary disease, in which malnutrition accelerates airway remodeling and increases mortality through systemic inflammation and immune suppression[21]. Importantly, given the retrospective design of this study, causality cannot be established. A reduced GNRI may represent a risk marker or surrogate of underlying metabolic or inflammatory status rather than a direct causal factor. Prospective longitudinal studies are necessary to clarify temporal relationships and determine whether improving nutritional status modifies adenoma risk.

Multivariable logistic regression analysis corroborated these findings. After adjustment for established confounders, age (OR = 1.037), TG (OR = 1.468), and CEA (OR = 1.254) emerged as independent risk factors, whereas GNRI (OR = 0.692), serum albumin level (OR = 0.815), and BMI (OR = 0.889) conferred significant protection (all P < 0.05). Advanced age is associated with accumulated genomic damage and waning DNA-repair capacity. Elevated TG levels may disrupt lipid-mediated signaling and promote epithelial hyperproliferation[22]. CEA, a glycoprotein overexpressed in premalignant and malignant colorectal tissues, likely reflects early molecular alterations rather than nonspecific inflammation. Conversely, adequate serum albumin ensures oncotic pressure, ligand transport, and immune competence; an optimal BMI signifies metabolic equilibrium and preserved muscle mass; and GNRI integrates visceral protein reserve and weight stability, thereby capturing the net nutritional milieu more comprehensively than either constituent alone[23-26].

ROC analysis demonstrated the superior discriminative performance of GNRI: AUC 0.874 (95%CI: 0.77-0.92), significantly higher than albumin alone (0.743) or BMI alone (0.656). At the optimal cutoff of 95.6, GNRI yielded 84.5% sensitivity and 81.2% specificity - performance metrics that compare favorably with established noninvasive tests such as fecal immunochemical testing. The incremental value of GNRI probably stems from its dual capture of protein availability and energy balance, thereby overcoming the long half-life and hepatic/inflammatory confounding of isolated albumin, as well as the inability of BMI to distinguish adiposity from lean mass or to reflect protein kinetics. Analogous benefits have been reported in chronic obstructive pulmonary disease and heart failure cohorts, where GNRI predicts exacerbations and mortality more accurately than its individual components[27-30].

Therefore, selection bias should be carefully considered. In this study, participants voluntarily underwent elective colonoscopy as part of a health screening program. Individuals willing to undergo invasive procedures may have greater health awareness, preexisting gastrointestinal symptoms, or perceived personal risk, potentially leading to an overestimation of adenoma detection rates. This cohort may not be representative of the general asymptomatic screening population. Future population-based prospective studies are required to validate the generalizability of these findings.

Unlike the fecal immunochemical test, which detects occult bleeding, the GNRI reflects the nutritional and metabolic status of the host. These tools capture different biological dimensions of colorectal neoplasia risk and may therefore be complementary rather than competitive. GNRI calculation requires only serum albumin and body weight, both routinely measured in annual health examinations, potentially allowing opportunistic risk stratification without additional procedural burden. The GNRI can be incorporated into multiparameter risk models combining age, family history, metabolic indicators, and fecal immunochemical test results to refine colonoscopy referral strategies. Cost-effectiveness analyses and head-to-head comparisons with established non-invasive screening tools are required before clinical implementation.

This study has some limitations. The modest sample size (n = 175) and retrospective design increase the risk of selection and information bias. Residual confounding by unmeasured dietary factors, physical activity, or microbiota signatures cannot be excluded, and our single-center findings require external validation. Large-scale, multicenter prospective studies incorporating serial GNRI assessments and comprehensive molecular phenotyping are warranted to confirm causality and refine risk stratification algorithms. Furthermore, baseline characteristics of individuals who declined colonoscopy were unavailable, which limited our ability to assess the representativeness of the study population.

CONCLUSION

GNRI is a robust, inexpensive, and readily standardized predictor of colorectal adenomatous polyps in a health-screening setting. Its incorporation into routine risk assessment could rationalize colonoscopy referral, particularly in resource-limited environments, and provide a quantitative endpoint for nutritional interventions aimed at the primary prevention of colorectal cancer.