Colorectal cancer (CRC) is the fourth most common fatal cancer after lung, stomach, and liver cancers,1 and colorectal adenomatous polyps are considered precancerous lesions of CRC.2 Colorectal polyps are characterized by a high incidence, insignificant early symptoms, multiple influencing factors, and poor consistency between clinical manifestations and disease severity. Colorectal polyps often occur in asymptomatic populations without complaints of hematochezia, lower abdominal pain, or marked changes in bowel habits. Early screening and removal is beneficial; however, the high prices and technology difficulty of colonoscopy impede the implementation of CRC screening. It will be useful to screen out those who require mandatory colonoscopies using a noninvasive method and to establish a risk stratification system which makes screening more cost-effective. Combined admitted risk factors with examinee indicators detected in medical check-ups for stratification is considered as higher cost performance. At present, multiple CRC screening risk stratification models have already been validated, such as the Asia-Pacific Colorectal Screening (APCS) score system. However, the discriminative ability of the scoring model has frequently been deemed inadequate. New indicators need to be detected and validated to improve the discriminative ability of CRC risk stratification model.
Along with the change in lifestyle have come “rich people’s diseases” such as obesity, high blood pressure, gout, cardiovascular disease and diabetes, and CRC incidence and mortality continue to increase in China. In medical check-ups, more and more asymptomatic people start to focus on blood glucose, blood lipid, uric acid (UA), and other metabolic factors for early detection, early intervention and individualized treatment. Common research has long held that the occurrence, development, and carcinogenesis of colorectal adenomatous polyps are affected by many factors,3–5 such as age, obesity, smoking, and type 2 diabetes. A study from Taiwan clarified that smoking and high body mass index were risk factors for adenomatous and hyperplastic polyps in asymptomatic populations.6 Carcinoembryonic antigen (CEA) is expressed highly in a variety of malignant tumors and ~80% of CRCs.7 CEA and carbohydrate antigen 19-9 (CA 19-9) have been reported as risk factors for the recurrence of colorectal polyps.8 However, few studies have investigated the correlation between colorectal polyps and risk factors, such as metabolic factors and tumor markers, in asymptomatic populations undergoing medical check-ups. This study aimed to look for other examinee indicators detected in medical check-ups which may be useful in risk stratification of CRC, and to provide evidence to support mandatory colonoscopy in an asymptomatic population.
MATERIALS AND METHODS
Study Population
This study was conducted retrospectively at the Second Hospital of Shandong University (Shandong, China). Asymptomatic and healthy people who underwent voluntary colonoscopy on medical check-ups between May 2014 and December 2021 were included. The standard colorectal screening measures are based on the Technical Plan for Early Diagnosis and Early Treatment of Colorectal Cancer formulated by the Early Diagnosis and Early Treatment of Colorectal Cancer Project of National Health and Family Planning Commission in 2011 and updated in 2020. The guideline recommends CRC screening for general populations between the ages of 40 and 74 through direct colonoscopy every 5 to 10 years. Patients were excluded if they reported intestinal tract disease including hematochezia, lower abdominal pain, and marked changes in bowel habits. Patients with ulcerative colitis, Crohn disease, familial adenomatous polyps, or prior colonic surgery were also excluded.
The study was approved by the Medical Ethics Committee of the Second Hospital of Shandong University (Ethical approval number: KYLL-2022LW063). This study was exempt from the requirement of obtaining informed consent from the participants as data were collected from pre-existing records and had been anonymized to protect patient privacy.
Study Design
Data on the basic features of the study population were collected. The participants underwent blood tests, which included CEA, CA 19-9, serum UA, triglyceride (TG), high-density lipoprotein (HDL-C), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), total cholesterol (TCH), and low-density lipoprotein (LDL-C). The participants underwent colonoscopy performed by an experienced endoscopist. Bowel preparation was performed using compound polyethylene glycol electrolyte powder, with the same protocol as that used for diagnostic colonoscopy. Colorectal polyps were defined as protuberances in the lumen caused by the proliferation of the colonic mucosa. The polyp samples were processed, histologic slices were made, and hematoxylin and eosin (H&E) staining was used for pathologic diagnosis by an expert pathologist at our hospital. The pathologic classification of colorectal polyps3,9 included inflammatory polyps, hyperplastic polyps, adenomas, sessile serrated polyps, and traditional serrated adenomas. According to pathologic analysis, the participants were divided into a non-adenomatous polyp group (those with mainly inflammatory and hyperplastic polyps) and an adenomatous polyp group (those with adenomas, sessile serrated polyps, and traditional serrated adenomas). Participants with adenomas were also divided into a single and a multiple polyp group based on the number of adenomatous polyps. Considering that patients with cancer were rare in the health examination population in this study, they were not included.
Statistical Analysis
Data were statistically analyzed using SPSS 28.0 (IBM, Chicago, IL). The measurement data were expressed as mean ± SD, and comparisons between groups were performed using an unpaired t test. Categorical data are expressed as numbers and percentages, and comparison between groups were performed using a χ2 test. Cutoff value was calculated by receiver operating characteristic analysis. Risk factors for colorectal polyps were analyzed by binary logistic regression analysis. Statistical significance was set at P<0.05.
RESULTS
Colorectal Polyps were the Main Lesions Observed in Colonoscopy Findings in the Asymptomatic Population
A total of 933 asymptomatic people underwent colonoscopies during physical examination from May 2014 to December 2021. Various digestive diseases in asymptomatic populations were analyzed, including colorectal polyps (n=475), colitis and proctitis (n=80), CRC (n=4), hemorrhoids (n=357), melanosis coli (n=17), colonic diverticulum (n=59), and submucosal tumors (n=15). The incidence of colorectal polyps was the highest (50.91%) in the asymptomatic population. The incidence of various digestive diseases was compared between male and female, aged ≤40 and >40 years. The results showed that the incidence of polyps was higher in males (58.39%) than in females (35.22%; P<0.001) (Fig. 1); it also higher when people were >40 years old (55.06%) than when people were ≤40 years (25.76%, P<0.001, Fig. 1). Among all cases of colorectal polyps, 307 adenomas (64.63%), 132 non-adenomatous polyps (27.79%), and 36 other polyps (7.58%) were reported in this asymptomatic population (Fig. 2). Colorectal adenomas accounted for the main portion. White light image and pathology image of polyps were exhibited in Figure 3.
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FIGURE 1: The incidence of various digestive diseases in males and females, population ≤40 years and >40 years. SMT indicates submucosal tumor.
FIGURE 2: The apportion of different pathologic types for colorectal polyps. Adenomatous polyps: adenomas, sessile serrated polyps, and traditional serrated adenomas. Non-adenomatous polyps, including mainly inflammatory hyperplastic polyps Other polyps: No pathologic analysis was performed.
FIGURE 3: Representative white light image and pathologic image of colorectal polyps. A, Tubular adenoma (size of polyp: 0.7×0.6 cm). B, Tubular adenoma (×40 magnification). C, Traditional serrated adenoma (size of polyp: 1.0×0.5 cm). D, Traditional serrated adenoma (×40 magnification). E, Sessile serrated adenoma (size of polyp: 0.7×0.5 cm). F, Sessile serrated adenoma (×100 magnification). G, Hyperplastic polyp (size of polyp: 0.2×0.3 cm). H, Hyperplastic polyp (×100 magnification).
Comparison of Baseline Characteristics and Blood Tests Between the Polyp and Control Groups
In this study, 475 patients were enrolled in the polyp and 344 in the control group (including people who endured no lesions except hemorrhoids). The average age was 53.04±9.78 and 47.04±9.81 years for the polyp and control groups, respectively. The difference was significant (P<0.01). Significant differences were also found in sex, CEA level, HbA1c level, and UA level (P≤0.05). Although there were no significant differences in the levels of LDL-C, CA 19-9, TG, TCH, FBG, and HDL-C between the 2 groups (P>0.05), the levels of these blood tests in the polyp group were still higher than those in the control group, except for HDL-C (Table 1). The results were thus meaningful to some extent.
TABLE 1 -
Comparisons of Basic Characteristics and Blood Tests Between the Control and Polyp Group
|
|
|
Univariate analysis |
Multivariate analysis |
| Variables |
Control group (n=344) |
Polyp group (n=475) |
P
|
Odds ratio (95% CI) |
P
*
|
| Age (y)†
|
47.04±9.81 |
53.04±9.78 |
<0.01
|
4.233 (1.532, 1.694) |
0.005
|
| Sex (male, %)‡
|
190 (55.23%) |
369 (77.68%) |
<0.01
|
3.810 (1.754, 8.276) |
<0.01
|
| CEA (ng/mL) |
1.37±1.04 |
1.87±1.03 |
0.001
|
2.846 (1.400, 5.784) |
0.004
|
| CA 19-9 (ng/mL) |
11.26±11.21 |
14.41±9.91 |
0.144 |
|
|
| TG (mmol/L) |
1.58±2.32 |
1.73±2.13 |
0.318 |
|
|
| TCH (mmol/L) |
4.77±1.07 |
4.92±1.21 |
0.185 |
|
|
| LDL-C (mmol/L) |
2.73±0.78 |
2.86±0.88 |
0.15 |
|
|
| HbA1c (NGSP, %) |
5.76±0.52 |
6.26±1.51 |
0.041
|
|
|
| FBG (mmol/L) |
5.51±1.56 |
5.75±1.84 |
0.169 |
|
|
| HDL-C (mmol/L) |
1.30±0.32 |
1.23±0.30 |
0.092 |
|
|
| UA (μmol/L) |
321.57±89.60 |
342.18±87.92 |
0.050
|
1.651 (0.616, 4.427) |
0.319 |
Categorical variables, n (%); Continuous variables, mean±SD; Significant P-values are shown in bold text.
Cutoff value of CEA level was 1.435 ng/mL calculated by ROC analysis, and comparation between CEA>1.435 ng/mL and ≤1.435 ng/mL in multivariate analysis.
Cutoff value of UA level was 227.55 μmol/L calculated by ROC analysis, and comparation between UA >227.55 μmol/L and ≤227.55 μmol/L in multivariate analysis.
HbA1c level was not analyzed for small sample size.
*P, p-value by binary logistic regression analysis.
†Comparation between people >40 years and ≤40 years in multivariate analysis.
‡Comparation between male and female in multivariate analysis.
CA 19-9 indicates carbohydrate antigen; CEA, carcinoembryonic antigen; FBG, fasting blood glucose; HbA1c, Glycosylated hemoglobin; HDL-C, high-density lipoprotein; LDL-C, low-density lipoprotein; NGSP, National Glycohemoglobin Standardization Program; ROC, receiver operating characteristic; TCH, total cholesterol; TG, triglyceride; UA, uric acid.
Risk factors that showed statistically significant differences in the univariate analysis were analyzed in the binary logistic regression analysis. Age, sex, CEA level, HbA1c level, and UA level were associated with the occurrence of colorectal polyps (Table 1). The results showed that sex (men) [odds ratio (OR)=3.810, 95% CI: 1.754, 8.276, P<0.01], age (>40 y) (OR=4.233, 95% CI: 1.532,11.694, P=0.005), and CEA level (OR=2.846, 95% CI: 1.400, 5.784, P=0.004) were independent risk factors for colorectal polyps in the asymptomatic population. HbA1c was excluded owing to insufficient data available (12/344 in Control group; 38/475 in Polyp group).
Comparisons of Baseline Characteristics and Blood Tests Between the Adenomatous and Non-adenomatous Groups
In this study, 307 participants were enrolled in the adenomatous polyp group and 132 in the non-adenomatous polyp group. The levels of CEA, CA 19-9, UA, TG, and TCH were significantly higher in the adenomatous polyp group than in the non-adenomatous polyp group (P<0.05). The average age of participants in the adenomatous polyp group was higher than that in the non-adenomatous group; the difference between groups was not significant (P=0.057). Gender distribution, and the levels of HbA1c, HDL-C, LDL-C, FBG did not differ significantly between the adenomatous and non-adenomatous polyp groups (P>0.05).
As shown in Table 2, TG, TCH, CEA, UA, and CA 19-9 levels were associated with colorectal adenomatous polyps. The binary logistic regression analysis showed that CEA levels (OR =2.458, 95% CI: 1.047,5.769, P=0.039) were independent risk factors for the occurrence of colorectal adenomatous polyps. Participants with CA 19-9 were excluded because of insufficient data available (32/307 in adenomatous group; 22/132 in non-adenomatous group).
TABLE 2 -
Comparisons of Basic Characteristics and Blood Tests Between the Adenomatous Group and Non-adenomatous Group
|
|
|
Univariate analysis |
Multivariate analysis |
| Variables |
Adenomatous group (n=307) |
Non-adenomatous group (n=132) |
P
|
Odds ratio (95% CI) |
P
*
|
| Age (y) |
53.04±9.50 |
51.11±9.73 |
0.057 |
|
|
| Sex (male, %) |
236 (76.87%) |
104 (78.79%) |
0.660 |
|
|
| CEA (ng/mL) |
2.04±1.07 |
1.55±0.89 |
0.012
|
2.458 (1.047, 5.769) |
0.039
|
| CA 19-9 (ng/mL) |
16.55±10.75 |
11.75±8.79 |
0.049
|
|
|
| UA (μmol/L) |
315.36±74.06 |
365.49±60.93 |
<0.01
|
0.936 (0.213, 4.120) |
0.930 |
| TG (mmol/L) |
2.01±2.53 |
1.30±1.11 |
0.019
|
1.782 (0.721, 4.404) |
0.211 |
| TCH (mmol/L) |
5.13±1.29 |
4.63±0.97 |
0.010
|
1.470 (0.571, 3.787) |
0.424 |
| LDL-C (mmol/L) |
2.94±0.87 |
2.79±0.88 |
0.193 |
|
|
| HbA1c (NGSP, %) |
6.38±1.80 |
6.04±0.51 |
0.196 |
|
|
| HDL-C (mmol/L) |
1.21±0.29 |
1.26±0.34 |
0.215 |
|
|
| FBG (mmol/L) |
5.89±2.16 |
5.52±1.15 |
0.113 |
|
|
Categorical variables, n (%); Continuous variables, mean±SD; Significant P-values are shown in bold text.
Cutoff value of CEA level was 1.435 ng/mL calculated by ROC analysis, and comparation between CEA>1.435 ng/mL and ≤1.435 ng/mL in multivariate analysis.
Cutoff value of UA level was 227.55 μmol/L calculated by ROC analysis, and comparation between UA >227.55 μmol/L and ≤227.55 μmol/L in multivariate analysis.
Cutoff value of TG level was 0.95 mmol/L calculated by ROC analysis, and comparation between TG>0.95 mmol/L and ≤0.95 mmol/L in multivariate analysis.
Cutoff value of TCH level was 5.45 mmol/L calculated by ROC analysis, and comparation between TCH>5.45 mmol/L and ≤5.45 mmol/L in multivariate analysis.
CA19-9 level was not analyzed for small sample size
*P, p-value by binary logistic regression analysis.
CA 19-9 indicates carbohydrate antigen; CEA, carcinoembryonic antigen; FBG, fasting blood glucose; HbA1c, Glycosylated hemoglobin; HDL-C, high-density lipoprotein; LDL-C, low-density lipoprotein; NGSP, National Glycohemoglobin Standardization Program; ROC, receiver operating characteristic; TCH, total cholesterol; TG, triglyceride; UA, uric acid.
Comparisons of Baseline Characteristics and Blood Tests in the Single and Multiple Adenoma Groups
In this study, 153 participants were enrolled in the single and 154 in the multiple adenoma group. The average age of the participants was 55.72±10.15 years and 50.27±7.17 years for the multiple and single adenoma groups, respectively; the difference was significant (P=0.003). Significant differences were also found in gender distribution (P=0.009). The CEA, HbA1c, and FBG levels in the multiple adenoma group were higher than those in the single adenoma group (P<0.05). Meanwhile, the HDL-C level in the multiple adenoma group was lower than that in the single group (P<0.05). Although there were no significant differences in the levels of CA 19-9, TG, cholesterol, LDL-C, and UA between the 2 groups (P>0.05), the blood tests levels in the multiple polyp group were higher than those in the single group, except for LDL-C. These results were also meaningful to some extent.
Age, sex, and CEA, HDL-C, FBG, and HbA1c levels were related to multiple colorectal adenomas (Table 3). However, no independent risk factors were identified for the occurrence of multiple colorectal adenomatous polyps. The results are presented in Table 3.
TABLE 3 -
Comparisons of Basic Characteristics and Blood Tests Between the Single and Multiple Adenomas Groups
|
|
|
Univariate analysis |
Multivariate analysis |
| Variables |
Single adenoma group (n=153) |
Multiple adenomas group (n=154) |
P
|
Odds ratio (95% CI) |
P
*
|
| Age (y)†
|
50.27±7.17 |
55.72±10.15 |
0.003
|
0.584 (0.046, 7.486) |
0.679 |
| Sex (male, %)‡
|
153 (70.59%) |
154 (83.12%) |
0.009
|
1.295 (0.261, 6.417) |
0.751 |
| CEA (ng/mL) |
1.82±0.77 |
2.31±1.32 |
0.031
|
0.667 (0.204, 2.183) |
0.503 |
| CA 19-9 (ng/mL) |
14.15±7.81 |
19.94±13.56 |
0.101 |
|
|
| UA (μmol/L) |
335.88±87.91 |
358.78±98.91 |
0.137 |
|
|
| TG (mmol/L) |
1.62±0.91 |
2.43±3.51 |
0.091 |
|
|
| TCH (mmol/L) |
5.08±1.00 |
5.19±1.55 |
0.361 |
|
|
| LDL-C (mmol/L) |
3.04±0.83 |
2.83±0.91 |
0.146 |
|
|
| HbA1c (NGSP, %) |
5.65±0.25 |
6.91±2.24 |
0.023
|
|
|
| HDL-C (mmol/L) |
1.27±0.32 |
1.15±0.24 |
0.027
|
0.674 (0.225, 2.022) |
0.482 |
| FBG (mmol/L) |
5.43±0.98 |
6.39±2.88 |
0.029
|
2.411 (0.795, 7.311) |
0.120 |
Categorical variables, n (%); Continuous variables, mean ± SD; Significant P-values are shown in bold text.
Median valve of HDL-C level was 1.22 mmol/L, and comparation between HDL-C level >1.22 mmol/L and ≤1.22 mmol/L in multivariate analysis.
Cutoff value of FBG level was 4.975 mmol/L calculated by ROC analysis, and comparation between FBG >4.975 mmol/L and ≤4.975 mmol/L in multivariate analysis.
HbA1c level was not analyzed for small sample size.
*P, p-value by binary logistic regression analysis.
†Comparation between people >40 years and ≤40 years in multivariate analysis.
‡Comparation between male and female in multivariate analysis.
CA 19-9 indicates carbohydrate antigen; CEA, carcinoembryonic antigen; FBG, fasting blood glucose; HbA1c, Glycosylated hemoglobin; HDL-C, high-density lipoprotein; LDL-C, low-density lipoprotein; NGSP, National Glycohemoglobin Standardization Program; ROC, receiver operating characteristic; TCH, total cholesterol; TG, triglyceride; UA, uric acid.
DISCUSSION
The incidence of colorectal cancer is still increasing significantly, and CRC is the highest among malignant tumors in China.10,11 A previous study6 demonstrated that the prevalence of hyperplastic and adenomatous colorectal polyps in asymptomatic Taiwanese individuals was 11.1% and 16.1%, respectively, which was lower than that in our study. High-quality endoscopy (magnifying endoscopy with narrow band imaging) adopted in our department of gastroenterology, which could improve the accuracy in diagnosing colorectal polyp, may account for this difference. Our prevalence rates were 14.1% and 32.9%, respectively, which is consistent with previous domestic reports.12–14 The importance of screening for and removal of colorectal polyps, especially adenomas, is evident. Colorectal polyps, including adenomas, are concealed in asymptomatic, healthy individuals. Therefore, investigation of the relevant risk factors for colorectal polyps in asymptomatic individuals, early colonoscopy screening, and colonoscopic resection of polyps are crucial. At present, lots of questions related to CRC screening indeed need to be addressed, including the cost effectiveness, quality control, and so on. In this context, demarcating risk stratification in asymptomatic populations is helpful to improve screening efficiency which allows for prioritizing colonoscopies effectively for populations at high risk for CRC. Multiple scoring models for risk stratification of populations undergoing CRC screening have been developed 15; however, new indicators need to be integrated and validated to improve the discriminative ability of these models.
Advanced age is a popular risk factor for polyp development. With 1 year older, the risk of multiple colorectal polyps increases by 1.03 times.16 The United States Preventive Services Task Force (USPSTF) recommends that people >45 years of age undergo colonoscopy. In our country the guideline17 recommends that the general population >40 years undergo routine colonoscopy, but more clinical evidence should be offered to support this proposal. In this study, the incidence of polyps in the population aged >40 years was almost 2.0 times higher than that in those aged < 40 years. Age was an independent predictor of colorectal polyps. Although older age is related to the occurrence of multiple adenomas, it is not an independent factor. Men were more likely to have polyps than women, especially multiple adenomas. Male sex was an independent predictor of colorectal polyps in this study. This may be due to poor dietary habits, smoking, and alcohol consumption in men.18 It is controversial whether endogenous sex hormones are contributors to sex disparities in the incidence and mortality rates of CRC.19,20
Tumor markers such as CEA and CA 19-9 have been well-known predictors for CRC21 and are used for the diagnosis or evaluation of diseases. CEA is a glycoprotein primarily involved in intercellular adhesion. It is produced by columnar and goblet cells and is found in normal colonic mucosa. CA 19-9 has been detected in many adenocarcinomas of the digestive tract, especially in pancreatic cancers. It is unusual for these markers to be investigated in association with polyps. The difference in CEA levels between the normal and polyp populations is controversial,22,23 and later research showed that as the CEA level increased in people with metabolic syndrome, the risk of developing colorectal polyps also increased. Another previous report8 claimed that CEA and CA 19-9 levels were related to the recurrence of colorectal polyps. Our results showed that CEA levels were higher in (i) the polyp group than in the control group, (ii) in the adenoma group than in the non-adenoma group, and (iii) in the single adenoma group than in the multiple adenoma group. We calculated the cutoff value of CEA by receiver operating characteristic analysis and divided the population into a high (>1.435 ng/mL) and a low CEA level group (≤1.435 ng/mL). CEA level (>1.435 ng/mL) was an independent factor for the development of adenomatous polyps. The CA 19-9 levels differed only between the adenoma and non-adenoma groups. The number of CA 19-9 samples was too small to be included in the multiple logistic regression analysis. Additional clinical data should be included in the analysis.
Previous studies23–25 have revealed a correlation between risk factors such as race, smoking, BMI, age, HP infection, metabolic status, and colorectal polyps. A high-fat, high-protein diet and a lack of physical exercise may be associated with a high incidence of colorectal polyps. Moreover, clinical studies do not always provide consistent results. The influence of risk factors such as age and CEA, CA 19-9, TG, cholesterol, UA, and FBG levels remains unclear in asymptomatic populations. Hyperlipidemia and obesity were considered as risk factors for CRC or advanced colorectal neoplasia (ACN) in the previous studies.26,27 A novel study from Korea suggested adults at ages <50 years diagnosed with diabetes have an increased risk of ACN compared with those without diabetes.28 Meanwhile, a recent study found a positive association of serum UA with CRC incidence.29 However, these studies were on basis of a surrogate outcome of neoplasia given the limited number of patients with ACN or CRC enrolled in the cohorts. In this study, although HbA1c and UA levels were significantly different between the control and polyp groups, binary logistic regression analysis showed that UA was not an independent risk factor. In addition, the HbA1c and CA 19-9 sample numbers were too few to be included. The levels of CA 19-9, UA, cholesterol, and TG in the adenomatous polyp group were significantly higher than those in the other groups, suggesting that hyperuricemia, hypercholesterolemia, and hyperlipidemia play an important role in the development of adenomatous polyps. Although HbA1c, HDL-C, and FBG levels, as well as age, and sex have been associated with the number of adenomas, no independent factors have been suggested.
Our study had some noteworthy limitations. The first and main limitation was the study’s single-center design, which may limit the generalizability of our observations to other colonoscopy studies. Further multi-center studies are required to confirm our findings. The second limitation was that of potential selection bias, a result of its observational and retrospective design. For the effects of our small sample size to be negated, prospective studies should be conducted on larger numbers of asymptomatic patients.
CONCLUSION
In summary, serum CEA level (>1.435 ng/mL) was independent risk factors for colorectal polyps and related to the occurrence of colorectal adenomas. It may be conducive to improve discriminative ability of CRC risk stratification model. Abnormal metabolic status, including elevated TG, TCH, UA, and FBG levels and decreased HDL-C levels, may influence the development of colorectal adenomas which require further investigations.
ACKNOWLEDGMENTS
The authors appreciate all of the participants who underwent colonoscopy in the physical examination. The authors also show their appreciation to their colleagues at the Second Hospital of Shandong University. The authors would like to thank Editage (http://www.editage.cn) for English language editing.
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