Association between lifestyle factors and disease progression in patients with colorectal polyps and early-stage cancer

Abstract

BACKGROUND

Colorectal cancer (CRC) typically progresses from benign colorectal polyps, which represent a precursor to malignancy. Identifying the factors influencing this progression is crucial for early intervention and prevention. Although genetic and environmental factors have been widely studied, the role of lifestyle factors such as physical activity, diet, smoking, sleep, and stress remains underexplored, especially in patients with early stage CRC or polyps. Recent evidence suggests that lifestyle behaviors may influence cancer progression by modulating inflammatory pathways, metabolic health, and immune function. For instance, high levels of physical activity are linked to a reduced risk of CRC development, whereas poor dietary habits, smoking, and inadequate sleep have all been implicated in increased cancer risk and progression. Moreover, early-stage CRC patients, who are often asymptomatic or have minimal symptoms, may particularly benefit from lifestyle modifications to slow disease progression and improve overall prognosis. The gap in understanding the specific influence of these lifestyle factors on colorectal polyps and early stage cancer progression underscores the need for comprehensive studies. By assessing several modifiable lifestyle factors and their association with disease progression, clinicians can identify practical intervention points. These interventions could ultimately reduce the need for more aggressive treatments and improve the long-term outcomes in affected patients.

AIM

To investigate the association between lifestyle factors and disease progression in patients with colorectal polyps and early stage cancer.

METHODS

In this observational study conducted from January 2022 to December 2023, we recruited 120 patients with colorectal polyps or early stage cancer from Jiangshan People's Hospital. Lifestyle factors, including physical activity, dietary patterns, smoking status, sleep quality, and stress levels, were assessed using validated questionnaires. Disease progression was evaluated using standardized follow-up colonoscopies and pathological examinations. Cox proportional hazards models were used to analyze the association between lifestyle factors and disease progression after adjusting for potential confounders.

RESULTS

During the median follow-up of 18.4 months, 42 (35.0%) patients experienced disease progression. High levels of physical activity were associated with reduced progression risk [adjusted hazard ratio (HR) 0.55, 95% confidence interval (CI): 0.38-0.80, P = 0.002] compared to low activity levels. High adherence to a healthy dietary pattern showed similar protective effects (adjusted HR 0.62, 95%CI: 0.43-0.89, P = 0.009). Current smoking (adjusted HR 1.92, 95%CI: 1.35-2.73, P < 0.001) and poor sleep quality (adjusted HR 1.38, 95%CI: 1.05-1.82, P = 0.021) were associated with increased progression risk. The impact of lifestyle factors was particularly pronounced in patients younger than 60 years and those with multiple polyps at baseline.

CONCLUSION

This study demonstrated significant associations between lifestyle factors and disease progression in colorectal polyps and early stage cancer. Physical activity, dietary patterns, smoking status, and sleep quality have emerged as key modifiable factors influencing disease progression. These findings support the integration of lifestyle assessments and modifications in the clinical management of patients with colorectal neoplasia.

Key Words: Colorectal polyps; Disease progression; Lifestyle factors; Early stage cancer; Health behavior

Core Tip: This study highlights the significant role of lifestyle factors in the progression of colorectal polyps and early stage cancer. Physical activity, healthy dietary patterns, and good sleep quality are associated with a reduced risk of disease progression, whereas smoking and poor sleep quality increase this risk. These findings emphasize the importance of lifestyle modifications in managing colorectal neoplasia and suggest that lifestyle assessments should be integrated into the clinical care of patients with colorectal polyps or early stage cancer.

INTRODUCTION

Colorectal cancer (CRC) is one of the most significant global health challenges, ranking as the third most common cancer worldwide and the second leading cause of cancer-related mortality[1]. The progression from colorectal polyps to early stage cancer represents a critical window for intervention and prevention, with recent epidemiological data suggesting that approximately 70%-90% of CRCs develop from adenomatous polyps[2]. This adenoma-carcinoma sequence typically spans 10-15 years, providing a substantial opportunity for lifestyle interventions that could potentially alter the disease trajectory[3].

Recent evidence has shown that lifestyle factors play crucial roles in the development and progression of colorectal neoplasia. Meta-analyses have shown that adherence to healthy lifestyle patterns, including balanced dietary habits, regular physical activity, and smoking cessation, is associated with a 30%-50% reduction in CRC risk[4]. Furthermore, emerging research suggests that these lifestyle factors may influence the progression rate of polyps to early stage cancer, although the exact mechanisms are unclear[5].

The gut microbiome has emerged as a critical mediator in the relationship between lifestyle factors and colorectal disease progression. Studies indicate that dietary patterns, physical activity levels, and other lifestyle behaviors can significantly alter the composition and function of the gut microbiota, potentially influencing inflammatory responses and cellular proliferation in the colonic mucosa[6]. Modern molecular analyses have revealed that specific microbial signatures associated with different lifestyle patterns may predict the risk of polyp progression and early cancer development[7].

The socioeconomic burden of CRC management, particularly in the context of the aging global population, highlights the urgent need for cost-effective preventive strategies. Recent economic analyses suggest that lifestyle interventions could potentially reduce healthcare costs associated with CRC treatment by 20%-30%[8]. However, the implementation of such interventions requires a thorough understanding of the specific lifestyle factors that most significantly affect disease progression[9].

Despite a growing body of evidence supporting the role of lifestyle factors in CRC prevention, there remains a significant gap in our understanding of how these factors specifically influence the transition from polyps to early stage cancer. Although previous studies have examined lifestyle interventions for primary prevention or advanced disease settings, few have focused on the critical window between polyp identification and early cancer development[10]. Additionally, most existing research has been conducted on Western populations, leaving uncertainty about the generalizability of the findings to diverse ethnic and cultural contexts[11].

Rapid advancements in molecular diagnostics and precision medicine have created new opportunities for understanding the interactions between lifestyle factors and disease progression at the molecular level. Recent studies utilizing multi-omics approaches have identified specific molecular pathways through which lifestyle factors may influence polyp progression and early cancer development[12]. These insights suggest that lifestyle interventions tailored to individual molecular profiles may offer more effective strategies for preventing disease progression[13].

Modern analytical techniques have enabled more sophisticated approaches to studying lifestyle-disease interactions. Artificial intelligence and machine learning algorithms have begun to reveal complex patterns in lifestyle-disease relationships that were previously undetectable through traditional statistical methods[14]. These advanced analytical approaches highlight the importance of simultaneously considering multiple lifestyle factors rather than examining individual behaviors in isolation[15].

The clinical management of colorectal polyps and early stage cancer has evolved significantly in recent years, with an increasing emphasis on risk stratification and personalized surveillance strategies. Current guidelines recommend considering lifestyle factors in risk assessment; however, considerable uncertainty remains regarding how to optimally integrate lifestyle data into clinical decision-making[16]. This uncertainty is particularly pronounced when managing patients with different polyp characteristics and varying risk profiles[17].

The present study aimed to investigate the association between lifestyle factors and disease progression in patients with colorectal polyps and early stage cancer through a multicenter observational study conducted between 2022 and 2023. By examining approximately 120 cases, this study seeks to contribute to the growing body of evidence regarding the role of modifiable lifestyle factors in disease progression and to inform more effective preventive strategies in clinical practice.

MATERIALS AND METHODS

Study design and setting

This observational study was conducted at Jiangshan People's Hospital from January 2022 to December 2023. The research protocols were approved by the institutional review boards of all participating centers and written informed consent was obtained from all participants.

Study population

Patients aged 18 years and older who were diagnosed with colorectal polyps or early-stage CRC through colonoscopy and subsequent pathological confirmation were eligible for participation in the study.

Inclusion criteria: (1) Histologically confirmed colorectal polyps or early-stage CRC (Tis-T1); (2) Age ≥ 18 years; (3) Ability to provide informed consent; (4) Completion of lifestyle assessment questionnaires; and (5) Regular follow-up attendance.

Exclusion criteria: (1) History of inflammatory bowel disease; (2) Previous colorectal surgery; (3) Advanced stage CRC (T2 or higher); (4) Hereditary CRC syndromes; (5) Severe comorbidities affecting lifestyle assessment; (6) Pregnancy or lactation; and (7) Inability to complete questionnaires independently.

Data collection and assessment

Baseline demographic and clinical data were collected using standardized electronic case report forms. Medical records were reviewed to obtain information on patient characteristics, family history, comorbidities, and medication use. All colonoscopy procedures were performed by experienced endoscopists who had performed at least 1000 colonoscopies. Endoscopic findings were documented using standardized reporting systems, including the Paris classification for polyp morphology and the narrow-band imaging International Colorectal Endoscopic classification for polyp characterization.

Lifestyle assessment

Comprehensive lifestyle assessment was conducted using validated questionnaires administered at baseline and during follow-up visits. Lifestyle factors evaluated included dietary habits, physical activity, smoking status, alcohol consumption, sleep patterns, and stress levels. Dietary habits were assessed using a semiquantitative food frequency questionnaire that had been validated for the study population. The questionnaire consisted of 120 food items and participants were asked to report their average frequency of consumption over the previous year.

Physical activity was evaluated using the International Physical Activity Questionnaire Long Form, which assesses activity across multiple domains, including occupational, transport-related, domestic, and recreational activities. Activity levels were converted to metabolic equivalent task minutes per week, according to established protocols.

Smoking status was categorized based on a detailed smoking history, including current smoking status, duration of smoking, average number of cigarettes per day, and time since cessation for former smokers. Alcohol consumption was quantified using a standardized alcohol consumption questionnaire that captured both the frequency and quantity of different types of alcoholic beverages.

Sleep patterns were assessed using the Pittsburgh Sleep Quality Index, which evaluates seven components of sleep quality: Subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Stress levels were assessed using the Perceived Stress Scale, a widely validated instrument for measuring psychological stress.

Pathological assessment

All tissue specimens obtained during colonoscopy were processed according to standardized protocols. Histopathological examinations were performed by experienced gastrointestinal pathologists who were blinded to the patients' lifestyle data. Polyps were classified according to the WHO classification system, and early CRCs were staged according to the TNM classification system (8^th edition). Additional molecular characteristics, including microsatellite instability status and KRAS mutation analysis, were assessed when clinically indicated.

Follow-up protocol

The participants were followed up according to a standardized protocol, with follow-up intervals determined based on initial findings and risk stratification. Follow-up colonoscopies were scheduled based on the current clinical guidelines, with intervals ranging from 3 months to 3 years, depending on the initial findings. Lifestyle assessments were repeated during each follow-up visit and any changes in health status or medication use were documented.

Disease progression

Assessment of disease progression was defined as the development of new polyps, an increase in polyp size, advancement in histological grade, or progression to invasive cancer. All progression events were confirmed by endoscopic and pathological examinations. Time to progression was calculated from the date of the initial diagnosis to the date of documented progression or the last follow-up.

Statistical analysis

Statistical analyses were performed using the SPSS software (version 26.0; IBM Corporation, Armonk, NY, United States). Continuous variables were expressed as mean ± SD or median with interquartile range (IQR), depending on the distribution of the data. Categorical variables were presented as frequencies and percentages. The associations between lifestyle factors and disease progression were analyzed using Cox proportional hazards models with adjustment for potential confounding factors, including age, sex, body mass index, family history, and comorbidities.

Lifestyle factors were analyzed both individually and as composite scores. Principal component analysis was used to identify major lifestyle patterns, and cluster analysis was performed to identify distinct lifestyle profiles in the study population. The proportional hazard assumption was tested using Schoenfeld residuals. Missing data were handled using multiple imputation techniques when appropriate.

Time-varying covariates were incorporated into the analysis to account for lifestyle factor changes during the follow-up period. Sensitivity analyses were performed to assess the robustness of the findings to different analytical approaches and potential violations of model assumptions. Statistical significance was set at P < 0.05. All tests were two-sided.

RESULTS

Patient characteristics

Between January 2022 and December 2023, 142 patients were initially screened for eligibility. After applying the inclusion and exclusion criteria, 120 patients were enrolled in the study, and the baseline assessment was completed. The median follow-up duration was 18.4 months (IQR: 14.2-22.6 months). The mean age of the study population was 56.3 ± 12.4 years, with 52.5% being male. Baseline demographic and clinical characteristics of the study population are shown in Table 1.

Table 1 Baseline demographic and clinical characteristics of study participants.

Characteristic	Total (n = 120)
Age, years (mean ± SD)	56.3 ± 12.4
Sex, n (%)
Male	63 (52.5)
Female	57 (47.5)
BMI, kg/m² (mean ± SD)	24.8 ± 3.6
Educational level, n (%)
Primary school or below	15 (12.5)
Secondary school	48 (40.0)
College or above	57 (47.5)
Family history of CRC, n (%)	22 (18.3)
Comorbidities, n (%)
Hypertension	38 (31.7)
Diabetes mellitus	25 (20.8)
Dyslipidemia	42 (35.0)
Initial diagnosis, n (%)
Colorectal polyps	98 (81.7)
Early-stage cancer	22 (18.3)
Polyp characteristics (n = 98)
Number of polyps (median, IQR)	2 (1-3)
Size of largest polyp, mm (median, IQR)	12 (8-18)
Location, n (%)
Right colon	35 (35.7)
Left colon	41 (41.8)
Rectum	22 (22.5)

BMI: Body mass index; CRC: Colorectal cancer; IQR: Interquartile range.

Lifestyle patterns and risk factors

Analysis of lifestyle factors revealed distinct patterns in the study population. The distribution of major lifestyle factors and their relationships with disease characteristics are shown in Table 2.

Table 2 Distribution of lifestyle factors and their association with disease characteristics.

Lifestyle factor	Number (%)	Disease progression HR (95% confidence interval)	P value
Physical activity level
Low (< 600 MET-min/week)	45 (37.5)	1.00 (reference)	-
Moderate (600-3000 MET-min/week)	52 (43.3)	0.68 (0.45-0.92)	0.015
High (> 3000 MET-min/week)	23 (19.2)	0.51 (0.33-0.78)	0.002
Dietary pattern
Poor adherence to healthy diet	38 (31.7)	1.00 (reference)	-
Moderate adherence	56 (46.7)	0.72 (0.54-0.96)	0.024
High adherence	26 (21.6)	0.59 (0.41-0.85)	0.005
Smoking status
Never smoker	65 (54.2)	1.00 (reference)	-
Former smoker	32 (26.7)	1.28 (0.92-1.78)	0.142
Current smoker	23 (19.1)	1.85 (1.32-2.59)	0.001
Sleep quality
Good (PSQI ≤ 5)	48 (40.0)	1.00 (reference)	-
Poor (PSQI > 5)	72 (60.0)	1.45 (1.12-1.88)	0.005

PSQI: Pittsburgh Sleep Quality Index; HR: Hazard ratio.

Disease progression

During the follow-up period, 42 (35.0%) patients experienced disease progression. The median time to progression was 14.2 months (IQR: 10.8-17.6 months). Table 3 presents the disease progression patterns observed during the study period.

Table 3 Patterns of disease progression during follow-up.

Progression pattern	n (%)
New polyp development	26 (61.9)
Increase in polyp size	8 (19.0)
Histological progression	5 (11.9)
Progression to invasive cancer	3 (7.2)
Total progression events	42 (100.0)

Multivariate analysis of lifestyle factors and disease progression

After adjusting for potential confounding factors, several lifestyle factors were found to be significantly associated with disease progression. The results of the multivariate Cox proportional hazards analysis are presented in Table 4.

Table 4 Multivariate analysis of lifestyle factors associated with disease progression.

Variable	Adjusted HR (95%CI)1	P value
Physical activity (vs low)
Moderate	0.71 (0.52-0.97)	0.032
High	0.55 (0.38-0.80)	0.002
Dietary pattern (vs poor adherence)
Moderate adherence	0.76 (0.56-1.03)	0.078
High adherence	0.62 (0.43-0.89)	0.009
Current smoking (vs never)	1.92 (1.35-2.73)	< 0.001
Poor sleep quality	1.38 (1.05-1.82)	0.021
High stress level	1.45 (1.12-1.88)	0.005
BMI (per 5 kg/m² increase)	1.28 (1.06-1.55)	0.011
Age (per 10 years)	1.15 (0.98-1.35)	0.089
Male sex	1.22 (0.91-1.64)	0.186

¹Adjusted for age, sex, body mass index, family history of colorectal cancer, comorbidities, and baseline disease characteristics.

BMI: Body mass index; HR: Hazard ratio.

Subgroup analysis

Further analysis revealed that the association between lifestyle factors and disease progression varied among subgroups. The impact of lifestyle factors was particularly pronounced in patients younger than 60 years and those with multiple polyps at baseline. The interaction between different lifestyle factors demonstrated a cumulative effect, with patients who adhered to multiple healthy lifestyle factors showing significantly lower progression rates than those with poor adherence across multiple factors.

DISCUSSION

This multicenter observational study provides important insights into the association between lifestyle factors and disease progression in patients with colorectal polyps and early stage CRC. Our findings demonstrated significant relationships between specific lifestyle patterns and disease progression, with particular emphasis on physical activity, dietary habits, smoking status, and sleep quality.

The observed inverse relationship between physical activity levels and disease progression aligns with recent mechanistic studies showing that regular exercise modulates inflammatory pathways and immune responses in the colorectal mucosa[18]. The reduction in progression risk among patients with moderate-to-high physical activity levels [hazard ratio (HR) 0.71 and 0.55, respectively] is comparable to findings from a recent meta-analysis that reported similar protective effects of physical activity against colorectal neoplasia progression[19]. The dose-response relationship observed in our study suggests that even moderate levels of physical activity may confer significant benefits, which has important implications for patient counseling and lifestyle intervention strategies.

Our dietary pattern analysis revealed that high adherence to a healthy diet was associated with a 38% reduction in the risk of disease progression. This finding builds on emerging evidence from molecular studies demonstrating that dietary factors can influence epigenetic modifications and gut microbiome composition[20]. Recent metabolomic analyses have shown that specific dietary patterns can alter the colonic metabolome, potentially creating an environment that is less conducive to neoplastic progression[21]. The protective effect observed in our study was particularly pronounced in patients who maintained consistent dietary patterns throughout the follow-up period, suggesting the importance of sustained dietary modifications.

The strong association between current smoking and increased disease progression (HR 1.92) observed in our study provides additional evidence for the detrimental effects of tobacco use on colorectal neoplasia. Recent studies have identified specific smoking-related DNA methylation patterns in colorectal tissues that may accelerate the adenoma-carcinoma sequence[22]. The molecular mechanisms underlying this association have been further elucidated through studies demonstrating that tobacco-specific nitrosamines can directly influence cellular proliferation and survival pathways in colonic epithelial cells[23].

The relationship between sleep quality and disease progression revealed in our study adds to a growing body of evidence linking circadian rhythm disruption to colorectal neoplasia. Poor sleep quality was associated with a 38% increase in the risk of disease progression, consistent with recent findings from prospective cohort studies[24]. Mechanistic studies have demonstrated that disrupted sleep patterns can alter immune function and inflammatory responses, potentially creating a pro-tumorigenic environment[25]. The interactions between sleep quality and other lifestyle factors observed in our study suggest a complex interplay that may influence disease outcomes through multiple pathways.

Multivariate analysis revealed significant interactions among lifestyle factors, suggesting a synergistic effect on disease progression. This finding is consistent with recent systems biology approaches that have demonstrated how multiple lifestyle factors converge on common molecular pathways involved in colorectal carcinogenesis[26]. The cumulative effect of multiple healthy lifestyle factors observed in our study supports the concept of comprehensive lifestyle modification approaches, rather than targeting individual behaviors in isolation.

The stronger association between lifestyle factors and disease progression observed in younger patients (< 60 years) is particularly noteworthy given the increasing incidence of early onset colorectal neoplasia[27]. This age-specific effect may reflect differences in tumor biology or environmental susceptibility between younger and older patients, as suggested by recent molecular characterization studies of early-onset colorectal neoplasia[28].

The variation in lifestyle effects among patients with different polyp characteristics provides important insights into risk stratification. Patients with multiple polyps at baseline showed particularly strong associations between lifestyle factors and progression risk, consistent with recent findings suggesting that polyp multiplicity may reflect the underlying biological susceptibility to environmental factors[29]. This observation has implications for surveillance strategies and intensity of lifestyle interventions in different patient subgroups.

The stress-related findings of our study complement those of recent studies on psychoneuroimmunology and cancer progression. The observed association between high stress levels and increased progression risk (HR 1.45) aligns with mechanistic studies demonstrating that chronic stress modulates immune function and inflammatory responses in the colorectal mucosa[30]. The interaction between stress levels and sleep quality observed in our study suggests a potential pathway through which psychological factors influence disease progression[31].

A key strength of our study is the comprehensive assessment of lifestyle factors and their temporal changes during the follow-up period. The use of validated assessment tools and standardized protocols to evaluate disease progression enhanced the reliability of our findings. However, several limitations should be considered when interpreting the results. This exploratory cohort was not powered to detect HR < 0.60. The observational nature of the study precludes definitive causal inference, and a median follow-up of 18.4 months may not capture long-term progression patterns. Additionally, while we attempted to control for potential confounders, particularly unrecorded Non-steroidal anti-inflammatory drug use and lack of gut microbiota profiling, residual confounding factors cannot be completely ruled out.

CONCLUSION

Our study demonstrated significant associations between specific lifestyle factors and disease progression in patients with colorectal polyps and early stage CRC. Physical activity, dietary patterns, smoking status, and sleep quality have emerged as key modifiable factors influencing disease progression. The observed interactions between the different lifestyle factors suggest that comprehensive lifestyle modifications may provide optimal benefits to patients with colorectal neoplasia. These findings provide evidence-based support for incorporating lifestyle assessments and modifications into the clinical management of patients with colorectal polyps and early stage cancer.