High levels of carcinoembryonic antigen and smoking might be markers of colorectal adenoma in Korean males aged 40–49 years
Article information
Abstract
Background
Prevalence of adenoma in males aged 40–49 years in Korea was higher than expected. The aim of this study was to investigate the prevalence and risk factors of colorectal adenoma in males aged 40–49 years.
Methods
Total 1,902 asymptomatic subjects with a mean age of 47.9±6.7 years, who underwent a screening colonoscopy in a health promotion center of Myongji Hospital from 2010 to 2013 were enrolled in this study. We conducted a case-control study to determine the risk factors for adenoma. The subjects were classified into two groups (adenoma vs. controls). To validate the diagnostic value of carcinoembryonic antigen (CEA) for adenoma, area under the receiver operating characteristic curve (AUROC) was calculated.
Results
At least one colorectal adenoma was identified in 385 subjects (20.2%). Among these 385 subjects, 372 subjects were found to have a non-advanced adenoma, 13 subjects had an invasive adenoma. One subject had cancer. Male sex, age, smoking, metabolic syndrome, and elevated CEA level were significantly associated with a colorectal adenoma in univariate analysis. However, metabolic syndrome was not significant in multivariate analysis. In the male group, the AUROC of CEA for colorectal adenoma was 0.600 (0.543 to 0.656) in non-smokers under 50 years of age, and 0.615 (0.540 to 0.690) in smokers under 50 years of age.
Conclusion
Male sex, smoking, and high levels of CEA seem to be associated with colorectal adenoma. High levels of CEA and smoking may be diagnostic markers for any colorectal adenoma in Korean males aged 40–49 years.
INTRODUCTION
Colorectal cancer (CRC) incidence is rapidly increasing in many Asian countries, with rates approaching those of Western countries [1]. In South Korea, CRC was the 3rd most commonly diagnosed cancer in 2011, and the incidence of CRC has continued to increase in Korea, with a higher increase in men compared with women [2]. CRC screening is recommended for average-risk persons beginning at age 50 according to the guidelines of many professional societies [3–5]. The most reliable method for early detection of precancerous lesions among the CRC screening methods is colonoscopy which is associated with reduced CRC mortality [6].
Recently, it was reported that the prevalence of overall colorectal neoplasia in men aged 30–39 years exhibiting all risk factors was not lower than that in average-risk women aged >50 years [7]. In another study, the authors recommended earlier colorectal screening before 50 years in males with metabolic syndrome and history of smoking [8]. However, it was reported that the prevalence of adenomas was similar between individuals aged 40–49 years and those aged 50–59 years, although the prevalence of advanced neoplasia in the 50–59 years age group may be higher than that in the 40–49 years age group [9]. Also, colonoscopic detection of CRC is uncommon in asymptomatic persons 40–49 years of age [10]. In Korea, although the prevalence of non-advanced adenoma in males aged 40–49 years is higher than that in Western countries, the prevalence of advanced adenoma and adenocarcinoma is lower [11,12]. Although gender, smoking, and metabolic syndrome are important risk factors of colorectal neoplasm, the benefits of earlier screening colonoscopy in subjects with these risk factors remain unclear.
Therefore, the aim of the present study was to investigate the prevalence and risk factors of colorectal adenoma in males aged 40–49 years.
MATERIALS AND METHODS
1. Study population
The study population consisted of subjects who had undergone general check-ups at the health promotion center of Myongji Hospital, Goyang, Korea from January 2010 until December 2013 (n=29,310). We excluded subjects with the following characteristics: age under 40 years (n=9,124), subjects who did not receive a colonoscopy (n=5,467), subjects who received a colonoscopy more than 2 times (n=11,724), subjects who were not Korean (n=439), and subjects who had an incomplete colonoscopy result (n=133). Total 1,902 subjects who underwent first colonoscopy were included in the final analysis (Fig. 1).
Flow diagram for selection of study participants. Asymptomatic participants undergoing routine health check-up examinations from January 2010 until December 2013 at Myongji Hospital, Goyang, Korea (n=29,310).
The general check-ups included physical examination (including anthropometric measurement, body composition analysis, blood pressure), blood tests including metabolic profiles and tumor markers, such as carcinoembryonic antigen (CEA), esophagogastroduodenoscopy, abdominal sonography, plain chest radiography, and electrocardiography. An examinee could select additional screening tests, such as colonoscopy, computed tomography, and so on.
This study was approved by the institutional review board of the Myongji Hospital.
2. Data collection and definitions
All examinees were instructed to complete a self-administered health questionnaire before the health check-up. The questionnaire included past history of colorectal disease, drug history, family history of CRC, the amount of alcohol consumption, smoking status, and whether regular exercise was performed or not, and so on. If subjects had undergone two or more colonoscopies during the study period, result of the first colonoscopy was considered in the analysis. Heavy alcohol consumption was defined as drinking >80 g of alcohol per day. Smoking status was divided into three categories: (non-smoker, <20 pack years, ≥20 pack years)
The percentage of total body mass was calculated by body composition analysis (Inbody 720, BiospaceCo.Ltd., Seoul, South Korea). Arterial stiffness checked in the carotid artery was stratified into two stages (normal vs. abnormal) by pulse wave velocity (PWV) determined with an automatic device (Nippon Colin, Komaki, Japan). Body mass index was calculated as weight (kg) divided by height squared (m2).
Metabolic syndrome was diagnosed if three or more of the following five factors were satisfied [13]: (1) high blood pressure or use of antihypertensive drugs, (2) elevated triglycerides ≥150mg/dL or use of drugs for elevated triglycerides, (3) reduced high-density lipoprotein cholesterol level (<40mg/dL in males, <50mg/dL in females), (4) elevated fasting glucose or use of anti-diabetic medication, and (5) central obesity defined for the Korean population as a waist circumference of ≥90 cm for males and ≥85 cm for females [14].
Colonoscopies were performed by experienced gastroenterologists after bowel preparation with 4L of polyethylene glycol solution (Colyte, Taejun, Seoul, South Korea). Advanced adenoma was defined as adenomas with a diameter ≥10mm, and/or with villous component ≥25%, and/or with high grade dysplasia.
3. Statistical analysis
Data was divided into two groups (no adenoma vs. any adenoma). Continuous variables were compared using Student’s t-test. All continuous variables are expressed as means±S.E.M for each group. Categorical variables between the two groups were compared using the Pearson’s chi-squared test. For each variable, the odds ratio and 95% confidence interval were reported. The receiver operating characteristic curve (ROC curve) through logistic regression was calculated to obtain the cut-off value according to smoking status. p-values <0.05 were considered statistically significant. SPSS for Windows version 11 (SPSS Inc., Chicago, IL, USA) was used for all analyses.
RESULTS
1. Prevalence of colorectal adenoma in the study population
The study included 1,902 asymptomatic subjects who underwent health check-ups in a single endoscopy unit via screening colonoscopy (Fig. 1). Also, 1,391 (males:females= 967:424) subjects were 40–49 years of age, and 511 (males: females= 363:148) subjects were older than 49 years. Table 1 show the prevalence of colorectal adenoma in the study population. At least one colorectal adenoma was identified in 385 patients (20.2%). The prevalence of colorectal adenoma was 23.3% in the male group (311 out of 1,330), and 12.9% in the female group (74 out of 572). The prevalence of colorectal adenoma in subjects 40–49 years of age and in those ≥50 years was 18.4%(256 out of 1,391) and 21.2%(129 out of 511), respectively. Among the subjects with one or more colorectal neoplasms, 372 subjects were found to have a non-advanced adenoma, 13 subjects had an invasive adenoma. One patient had a cancer.
Prevalence of colorectal adenoma in the study population
Advanced adenoma (n=13) and colorectal adenocarcinoma (n=1) were found only in male subjects. Seven out of 13 subjects with advanced adenoma belong to male group 40–49 years of age (0.7%, 7 out of 967).
2. Risk factors of colorectal adenoma in the study population
Table 2 and 3 show the differences in demographics and clinical characteristics between the subjects with adenomatous polyps and controls. Male sex, smoking status, existence of metabolic syndrome, and arterial stiffness were significantly associated with colorectal adenoma in univariate analysis. The prevalence of overall colorectal adenoma increase as age, soft lean mass, systolic blood pressure, diastolic blood pressure, glycosylated hemoglobin (HbA1c), abdominal circumference, CEA level, and prostate specific antigen (PSA) level increased.
Characteristics of study participants by colorectal adenoma status (categorical variables)
Characteristics of study participants by colorectal adenoma status (continuous variables)
3. Risk analysis for colorectal adenoma by gender
The risk factors for colorectal adenoma in both genders are showed in Table 4 and 5. Age was significantly associated with colorectal adenoma regardless of gender. Arterial stiffness and CEA were significantly associated with colorectal adenoma in male subjects, but a similar effect was not seen in female subjects. PSA was significantly associated with colorectal adenoma in the male group. Smoking (≥20 pack years) and HbA1c tended to be associated with colorectal adenoma in the male group. In the female group, abdominal circumference was significantly associated with colorectal adenoma, but not in the male group.
Univariate analyses on the risk for overall colorectal adenoma according to sex groups
Univariate analyses on the risk for overall colorectal adenoma according to sex groups (continuous variables)
According to multiple logistic regression, adenoma was significantly associated with male sex, age, smoking, and CEA level (Table 6).
Multivariate analyses on the risk for overall colorectal adenoma
To validate the values of CEA for adenoma, area under the ROC curve (AUROC) was calculated (Table 7). AUROC of CEA for colorectal adenoma in non-smoking male subjects (n=585) under 50 years of age was 0.600 (95% CI, 0.543–0.656). AUROC of CEA for colorectal adenoma in smoking male subjects (n=376) under 50 years of age was 0.615 (95% CI, 0.540–0.690). The cut off value of high CEA level was 2.5 ng/mL in smokers and 1.0 ng/mL in non-smokers. The sensitivity and specificity of CEA level was 70.9% and 57.9% in smokers, and 76.8% and 64.8% in non-smokers.
AUROC of CEA for colorectal adenoma in male under 50 years of age
4. Prevalence of colorectal adenoma in males aged 40–49 years with risk factors
The prevalence of colorectal adenoma in young male subjects (40–49 years) was 22.4%(153/681). Among these subjects (n=153), the prevalence of colorectal adenoma was 44.8% (13/29) in smokers with an elevated CEA level and 25.2% (99/392) in non-smokers with an elevated CEA level. In subjects with a normal CEA level, the prevalence of colorectal adenoma was 15.4%(11/71) in smokers and 15.8%(30/189) in non-smokers. In contrast, the prevalence of colorectal adenoma in older female subjects (≥50 years) was 17.5%(16/91).
DISCUSSION
In our study, we found that 23.3% of subjects in the male group and 12.9% of subjects in the female group had more than one colorectal adenoma. In addition, the prevalence of colorectal adenoma in subjects 40–49 years of age and in those ≥50 years was 18.4% and 21.2%, respectively. The prevalence of colorectal adenoma was higher in the young male 40–49 years age group (22.4%) compared to the female 50–59 years age group (15.8%). In addition, all advanced adenomas were found in males. Although the results of the present study correspond with those of earlier Korean studies [11,12,15], the prevalence of colorectal adenoma was lower than that in other studies. Recently, it was reported that the prevalence of colorectal adenoma in the male 40–49 years age group in Korea was much higher (26.1–27.9%), compared with that in Western population [9,10,16]. The prevalence of colorectal adenoma in subjects aged 40–49 years including both males and females in Western countries is 12–15.3%. However in our study, the prevalence of advanced adenoma in subjects aged 40–49 years (0.7%) was much lower than that in Western population (1.5–3.5%). It was suggested that earlier detection and prior removal of polyps during screening programs in Korea may reduce the occurrence of advanced adenoma and adenocarcinoma. In addition, participants with poor bowel preparation were excluded from this study.
In multivariate analysis, adenoma was significantly associated with male sex, age, and CEA level in this study. There are many studies that investigated the risk factors of colorectal adenocarcinoma and adenoma. It was reported that 9 risk factors (sex, age, first-degree relatives with a history of CRC, cigarette smoking, alcohol consumption, red meat consumption, regular intake of nonsteroidal anti-inflammatory drugs, previous colonoscopy, and previous detection of polyps) were significantly associated with risk of advanced neoplasms [17]. Another several studies showed that male gender, positive occult blood, positive serology of Helicobacter pylori, and hypertriglycemia [18].
Hyperhomocysteinemia [19] and a higher level of brachial ankle PWV[20] were associated risk factors of colorectal adenoma in our study, the metabolic syndrome was not significantly associated with colorectal adenoma in multivariate analysis. There are many studies that support the relationship between colorectal adenoma and metabolic syndrome. It was reported that the metabolic syndrome components, in particular obesity, will significantly improve the efficacy of individual CRC screening [21]. Increasing levels of glucose, Homeostatic Model Assessment values, levels of HbA1c and C-peptide, and metabolic syndrome are significantly associated with prevalence of adenomas [22–28]. However, another study reported that no statistically significant associations with adenomas were observed for the markers of the metabolic syndrome, with the exception of a strong positive association for use of diabetes medications [29]. A further study is needed.
The main use of CEA in CRC is for surveillance following treatment of primary cancer [30]. However, in this study, there was a significant relationship between colorectal adenoma and CEA level. In addition, the prevalence of colorectal adenoma in male subjects aged 40–49 years with elevated CEA level was much higher than that in woman subjects above 50 years. Measurement of CEA level is relatively inexpensive and causes minimal inconvenience to the patients. Hence, its application to high risk subjects should be considered.
It was reported that among 40–49 year-old patients undergoing screening colonoscopy because of first degree relatives with polyps, the prevalence of adenomas was greater than that in a control population [31] and it was similar to that observed in older subjects with the same CRC risk [32]. Rectal bleeding warrants colonoscopy to detect advanced neoplasia in those aged 40–49 years, whereas non-bleeding symptoms, including some traditionally regarded as “alarm” symptoms, were associated with a much lower risk for neoplasia compared with the risk in screening patients aged 50–54 years [33]. In another study performed in USA, the author also suggested that screening in men between 45 and 49 years of age may be cost-effective compared to screening between 50 and 54 years of age depending on societal willingness to pay [34]. Hence, we should consider another risk factor before we select the candidate for colorectal screening.
Our study has several strengths. First, our study included all risk factors of colorectal adenoma including regular exercise, smoking, and alcohol. This is more difficult to achieve in large-scale population-based screening programs. Thus, our data was suitable for analysis of risk factors of colorectal adenoma. Second, the CEA level was compared with prevalence of colorectal adenoma. It was significantly associated with non-advanced colorectal adenoma. Hence, the CEA level can be used to select the right candidate for CRC screening, Third, all participants received a complete colonoscopy. Thus, we can minimize the possibility of missing colorectal adenoma.
Our study has several limitations. First, it was a retrospective study. There is a possibility of selection bias toward health-conscious individuals in the enrolled population, which may limit the generalization of the findings to the general population. Second, a relatively small number of participants were enrolled in this study. However, the number of men aged 40–49 years was not so small. Thus, the study did not lack data for analysis of risk factors in young male subjects Third, a small number of advanced adenoma and adenocarcinoma patients were included. As mentioned above, it is thought that we excluded the subjects with poor bowel preparation, and Korean CRC screening program can achieve early detection and removal.
In conclusion, male sex, smoking, and high CEA level seem to be associated with colorectal adenoma. High CEA level may be a diagnostic marker for any colorectal adenoma in Korean men aged 40–49 years. Further studies with a larger sample size are needed to confirm the exact role of CEA as a diagnostic marker of colorectal adenoma in Korean 40–49 years old. The prevalence of colorectal adenoma in Korean managed 40–49 years with risk factors was much higher than that in 50 year old women with average risk. Cost-effectiveness studies investigating the optimal age to start colonoscopy screening and etiological studies to identify the reasons for the increasing trend of colorectal adenomas in Koreans are needed.
Notes
Conflicts of interest
The authors have no conflicts of interest to disclose.