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Colorectal neoplasm in asymptomatic Asians: a prospective multinational multicenter colonoscopy survey
ORIGINAL ARTICLE: Clinical Endoscopy
Colorectal neoplasm in asymptomatic Asians: a prospective multinational multicenter colonoscopy survey Jeong-Sik Byeon, MD, Suk-Kyun Yang, MD, Tae Il Kim, MD, Won Ho Kim, MD, James Y. W. Lau, MD, Wai-Keung Leung, MD, Rikiya Fujita, MD, Govind K. Makharia, MD, Murdan Abdullah, MD, Ida Hilmi, MD, Jose Sollano, MD, Khay-Guan Yeoh, MD, Deng-Chyang Wu, MD, Min Hu Chen, MD, Pradermchai Kongkam, MD, Joseph J. Y. Sung, MD, for the Asia Pacific Working Group for Colorectal Cancer Seoul, Korea
Background: Colorectal neoplasm is rapidly increasing in Asia, but a guideline for screening is not available. Objective: To evaluate the characteristics of colorectal neoplasm in asymptomatic Asian subjects. Design: Prospective cohort study. Setting: Multinational multicenters, including both primary and referral centers in Asia. Patients: A total of 860 consecutive asymptomatic adults undergoing screening colonoscopy in 11 Asian cities from July 2004 to December 2004. Patients under 16 years old; those patients with a colorectal resection history, colonoscopies, or barium enema within 5 years; symptoms suggestive of colorectal diseases; and those who had undergone surveillance colonoscopy were excluded. Main Outcome Measurements: The incidence and distribution of colorectal neoplasm and advanced neoplasm. Results: The mean age (SD) was 54.4 11.6 years; 471 were men (54.8%). The prevalence of colorectal neoplasm and advanced neoplasm was 18.5% and 4.5%, respectively. Male sex, advancing age, and a family history of colorectal cancer were risk factors for advanced neoplasm. Of the 168 patients with colorectal neoplasm, 76 had distal neoplasm only (45.2%), 66 had proximal neoplasm only (39.3%), and 26 had both proximal and distal neoplasms (15.5%). Although the presence of distal advanced neoplasm was a significant risk factor for proximal advanced neoplasm, 14 of the 758 subjects without distal neoplasm had proximal advanced neoplasm (1.8%). Limitations: The small number of enrolled subjects, especially from certain ethnic groups. Conclusions: The overall prevalence of advanced colorectal neoplasm in asymptomatic Asians is comparable with the West. Male sex, advancing age, and a family history of colorectal cancer were associated with a higher risk of advanced neoplasm. (Gastrointest Endosc 2007;65:1015-22.)
Colorectal cancer is one of the most common malignancies in Western countries. According to the incidence and mortality data from the National Center for Health Statistics and the National Cancer Institute in the United States, colorectal cancer was estimated to comprise 10.7% of new cancer cases and was the second leading cause of cancer death in the United States in 2004.1 Efforts have been made to reduce mortality associated with this Copyright ª 2007 by the American Society for Gastrointestinal Endoscopy 0016-5107/$32.00 doi:10.1016/j.gie.2006.12.065
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important malignancy. Fecal occult blood screening for colorectal cancer has been shown to decrease the mortality from colorectal cancer.2-4 Colonoscopic polypectomy has been demonstrated to decrease the incidence of colorectal cancer in a large cohort study, as well as in clinical practice.5,6 Based on these findings and other studies about the prevalence of colorectal neoplasm,7-12 national and international professional bodies, including the American Gastroenterological Association, the British Society of Gastroenterology, and the World Gastroenterology Organization, established guidelines for colorectal cancer screening and surveillance.13-15 Volume 65, No. 7 : 2007 GASTROINTESTINAL ENDOSCOPY 1015
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In Asia, cancers of the stomach and the liver have traditionally predominated cancer incidence, and colorectal cancer was not common. During the past few decades, there has been a remarkable increase of colorectal cancer in Asian countries.16 In Aomori Prefecture in Japan, the age-adjusted incidences for colorectal cancer were 12.6 and 8.7 per 100,000 population for men and women, respectively, in 1974, and increased to 42.5 and 25.6 per 100,000 population, respectively, in 1991.17 In Hong Kong, China, the incidence of colorectal cancer in men increased from 40.0 per 100,000 in 1992 to 60.0 per 100,000 in 2002.18 Based on cancer death statistics reported by the South Korea National Statistical Office from 1983 to 2000 and projecting cancer mortality between 2001 and 2005, the National Cancer Center of Korea reported a 35% increase in colorectal cancer mortality in both men and women.19 Despite the rapid emergence of colorectal cancer in Asia, the epidemiology of this disease in this region remains unclear. We conducted a prospective, multinational, multicenter colonoscopy survey to assess the characteristics of colorectal neoplasm in Asia. The purpose of this study was to investigate the occurrence and location of colorectal neoplasm in asymptomatic Asian subjects. We also aimed to explore the risk factors for colorectal neoplasm, including the risk of advanced neoplasm in the proximal colon according to the findings in the distal colon.
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Capsule Summary What is already known on this topic d
Cancers of the stomach and the liver traditionally have been predominant in Asia, but a remarkable increase in the incidence of colorectal cancer has been seen in the last decades.
What this study adds to our knowledge d
In a prospective study of 860 consecutive asymptomatic Asian adults undergoing screening colonoscopy, the prevalence of colorectal neoplasm and advanced neoplasm was 18.5% and 4.5%, respectively, with male sex, advancing age, and family history of colorectal cancer being risk factors for advanced neoplasm.
pain that required medical evaluation, and those with a history of colorectal disease, such as polyp, cancer, or inflammatory bowel disease, were also excluded.
Study protocol
This was a pilot study to investigate the findings of colonoscopy in asymptomatic Asian subjects. We set out to conduct a prospective, multinational, multicenter study by using a database designed by the Asia Pacific Working Group for Colorectal Cancer. We aimed to include consecutive asymptomatic subjects above the age of 16 years, who were undergoing colonoscopy as a screening procedure referred to 17 centers from 11 Asian cities (Bangkok, Guangzhou, Hong Kong, Jakarta, Kuala Lumpur, Manila, New Delhi, Seoul, Singapore, Taipei, and Tokyo) over a period of 6 months. Because there is no national guideline for colorectal cancer screening in Asian countries, asymptomatic subjects who came forward requesting colonoscopy were recommended by their family members or primary care physicians. Self-referred young subjects (less than the age of 50 years) usually had a family history of colorectal cancer. We excluded subjects who had undergone colorectal imaging (including sigmoidoscopy, colonoscopy, or barium enema) within the previous 5 years, those with a history of colorectal surgery, and those colonoscopic examinations that failed to reach the cecum. Subjects with symptoms of lower-GI tract disease, including rectal bleeding, a change in bowel habits, or lower abdominal
Eligible persons who provided informed consent completed detailed questionnaires that covered a personal history of colorectal diseases; colorectal examination; and colorectal surgery; and a family history of cancer, including colorectal cancer. All colonoscopies were performed at the participating centers by experienced colonoscopists. During the examination, all polypoid lesions were documented for location and size. The distal colon was defined as 40 cm from the anal verge. The proximal colon was defined as the splenic flexure and the more proximal portions of the colon. The size of each polyp was estimated with the use of an 8-mmdiameter open-biopsy forceps. All the polyps were biopsied or polypectomized, and the obtained specimens were sent to local pathology laboratories at the participating centers for the histologic evaluation. Colorectal neoplasm was classified according to World Health Organization criteria.20 Advanced colorectal neoplasm was defined as an adenoma with a diameter of 10 mm or more, a villous adenoma (ie, at least 25% villous), an adenoma with high-grade dysplasia, or invasive cancer. Invasive cancer was defined as the invasion of malignant cells beyond the muscularis mucosa. Patients were classified on the basis of their most advanced lesion to determine the prevalence of pathologic features. For example, a patient with a villous adenoma and a tubular adenoma was classified as having a villous adenoma. All colonoscopy and histology results of included subjects were registered into a centralized database. The prevalence of all neoplasms and advanced colorectal neoplasm was determined. Risk factors for the presence of colorectal neoplasm were evaluated in terms of sex, age, family history of colorectal cancer, and ethnicity. The distribution
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PATIENTS AND METHODS Subjects
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TABLE 1. Age distribution of the 860 subjects
TABLE 2. Ethnic distribution of the 860 subjects
Age group, y
No. (%)
Ethnic group
20-39
86 (10.0)
Korean
382 (44.4)
40-49
209 (24.3)
Chinese
355 (41.3)
50-59
271 (31.5)
Filipino
57 (6.6)
60-69
214 (24.9)
Thai
22 (2.6)
70-79
64 (7.4)
Japanese
13 (1.5)
80-90
16 (1.9)
White
12 (1.4)
Indian
11 (1.3)
Malay
5 (0.6)
Indonesian
3 (0.3)
of colorectal neoplasm was also analyzed, and the risk of proximal neoplasm associated with distal colorectal lesions was determined. This study was carried out in accordance with the Helsinki Declaration.21
Statistical analysis Statistical analyses were performed with SPSS (version 11.5; SPSS Inc, Chicago, Ill). Continuous data about subject characteristics and outcomes were compared with the use of the Student t test and the Mann-Whitney U test. The Pearson c2 test or the Fisher exact test was used for the proportion analysis of categorical data. We calculated the relative risk and 95% confidence intervals (CI) in the analysis of the risk of colorectal neoplasm. A multiple logistic regression model was used to analyze the risk factors for colorectal neoplasm. All P values were 2-tailed, and a P value less than .05 was considered statistically significant.
RESULTS Characteristics of study population From July 2004 to December 2004, a total of 7290 subjects underwent a colonoscopy in the 17 participating centers. There were 860 asymptomatic adults who underwent colonoscopy and were analyzed in this study. Among them, 471 were men (54.8%). The mean age (SD) was 54.4 11.6 years (range, 20-90 years). In this cohort, 565 subjects (65.7%) were 50 years or older. There were 9 ethnic groups (Chinese, Indian, Indonesian, Japanese, Korean, Malay, Filipino, Thai, and white); Korean and Chinese were the 2 most common ethnic groups in this cohort. A total of 109 subjects (12.7%) had a positive history of colorectal cancer in their first-degree relatives. The distributions of age and ethnic groups of the study population are shown in Tables 1 and 2.
Prevalence of colorectal neoplasm Among the 860 asymptomatic subjects, 168 (18.5%) were found to have colorectal neoplasm. Advanced colowww.giejournal.org
No. (%)
rectal neoplasm was detected in 39 patients (4.5%), and invasive cancers were found in 9 patients (1.0%). The prevalence of colorectal neoplasm was higher in men (106/471 [22.5%]) than in women (62/389 [15.9%]) (P Z .016). Colorectal neoplasm was detected in 135 of 565 subjects (23.9%) with an age of 50 years or older, and the prevalence was significantly higher than that of those less than 50 years (33/295 [11.2%]; P ! .001). The prevalence of colorectal neoplasm increased as the age of subjects increased (P ! .001) (Fig. 1). The prevalence of colorectal neoplasm tended to be higher in the subjects with a positive history of colorectal cancer in their firstdegree relatives than in those without a family history of colorectal cancer: 27/109 (24.8%) versus 141/751 (18.8%), respectively. However, the difference did not reach statistical significance in univariate analysis (P Z .140). The prevalence of advanced colorectal neoplasm demonstrated similar features with that of overall neoplasms in terms of sex, age, and family history of colorectal cancer. The characteristics of prevalence of colorectal neoplasm are summarized in Table 3. With multivariate analysis, by using logistic regression model, male sex, advancing age, a positive history of colorectal cancer in the first-degree relatives, and the ethnicity of Korean or Japanese stand out to be significant risk factors for colorectal neoplasm (Table 4). Male sex, advancing age, and a positive history of colorectal cancer in the firstdegree relatives also increased the risk of advanced colorectal neoplasm (Table 5).
Topographical distribution of colorectal neoplasm Of the 168 patients with colorectal neoplasm, 76 (45.2%) had their neoplasm only in the distal colon. Sixty-six patients (39.3%) had neoplasm found only in the proximal colon, and 26 (15.5%) had their neoplasm found in both the proximal and the distal colon. Of the 39 patients with advanced colorectal neoplasm, 19 Volume 65, No. 7 : 2007 GASTROINTESTINAL ENDOSCOPY 1017
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TABLE 4. Risk factors for colorectal neoplasm
Male sex Age
OR (95% CI)
P
1.5 (1.1-2.2)
.019
1.05 (1.03-1.07) .001
Family history of colorectal cancer*
2.5 (1.5-4.2)
Ethnicity Chinese
Figure 1. Prevalence of overall colorectal neoplasm according to age. As the age increased, the prevalence of colorectal neoplasm increased (P ! .001).
TABLE 3. Patients with colorectal neoplasm stratified by sex, age, and family history of colorectal cancer (CRC)
Overall neoplasm Prevalence, no. (%)
P
106 (22.5)
Female (n Z 389)
62 (15.9)
.016
.019
Korean
2.0 (1.3-2.9)
.001
Filipino
0.3 (0.1-1.0)
.056
Indian
0.3 (0.0-2.4)
.250
Indonesian
0.0 (0.0, d)
.999
Malay
0.0 (0.0, d)
.999
Thai
0.2 (0.0-1.3)
.084
White
1.9 (0.5-7.4)
.371
*A family history of colorectal cancer was defined as 1 or more affected first-degree relatives.
Advanced neoplasm Prevalence, no. (%)
P
28 (5.9)
.029
TABLE 5. Risk factors for advanced colorectal neoplasm
Male sex Age
11 (2.8)
Age 33 (11.2)
R50 y (n Z 565)
135 (23.9)
!.001
6 (2.0)
.001
33 (5.8)
First-degree family history of colorectal cancer* 27 (24.8)
Absent (n Z 751)
141 (18.8)
.140
8 (7.3)
OR (95% CI)
P
2.3 (1.1-4.8)
.023
1.04 (1.01-1.08)
.005
3.2 (1.3-7.7)
.009
Ethnicity Chinese
Present (n Z 109)
Reference 4.2 (1.3-13.9)
Family history of colorectal cancer*
!50 y (n Z 295)
.001
Japanese
Sex Male (n Z 471)
.001
.807 Reference
Japanese
2.7 (0.3-23.3)
.364
Korean
1.9 (0.9-4.0)
.069
Filipino
0.6 (0.1-4.7)
.613
Indian
1.7 (0.2-15.4)
.647
Indonesian
0.0 (0.0)
.999
Malay
0.0 (0.0)
.999
Thai
0.0 (0.0)
.998
White
0.0 (0.0)
.999
.139
31 (4.1)
*A family history of colorectal cancer was defined as 1 or more affected first-degree relatives.
*A family history of colorectal cancer was defined as 1 or more affected first-degree relatives.
(48.7%) had their advanced neoplasm in the distal colon. Seventeen patients (43.6%) had advanced neoplasm found only in the proximal colon, and 3 (7.7%) had their advanced neoplasm in both the proximal and the distal colon.
Of the 102 patients with distal neoplasm, 26 (25.5%) had proximal neoplasm as well. However, 66 of 758 subjects (8.7%) without colorectal neoplasm in the distal colon had colonic neoplasm in the proximal colon (P ! .001) and 14 (1.8%) had advanced neoplasm in the
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TABLE 6. Risk of advanced neoplasm in the proximal colon according to the colonoscopic findings in the distal colon Colonoscopic finding in distal colon
Total no. patients
No. patients with proximal advanced neoplasm
Adjusted relative risk (95% CI)*
720
13
1.0
Hyperplastic polyp
38
1
1.3 (0.2-10.4)
Nonadvanced neoplasm
80
3
1.7 (0.5-6.3)
Advanced neoplasm
22
3
6.3 (1.6-25.4)
No polyp
*The relative risk was adjusted for age and sex. The group of patients with no polyp in the distal colon was the reference group.
TABLE 7. Risk factors for proximal advanced neoplasm in 720 subjects without any polyps in the distal colon OR (95% CI)
P
Male sex
3.5 (0.9-13.4)
.071
Age R 50 y
3.1 (0.7-12.8)
.122
Family history of colorectal cancer*
6.0 (1.3-26.6)
.019
Ethnicity
d
.600
*A family history of colorectal cancer was defined as 1 or more affected first-degree relatives.
proximal colon. When the risk of proximal advanced neoplasm was analyzed according to the colonoscopy findings in the distal colon, the presence of distal advanced neoplasm was the only significant risk factor for proximal advanced neoplasm (Table 6). A positive history of colorectal cancer in first-degree relatives significantly increased the risk of proximal advanced neoplasm in 720 subjects without any distal polyp (Table 7). Of the 20 patients with proximal advanced neoplasm, only 7 (35.0%) had 1 or more colorectal neoplasm in the distal colon. Although the prevalence of all colorectal neoplasm (22.5% vs 15.9%, P Z.016) and advanced neoplasm (5.9% vs 2.8%, P Z.029) were significantly higher with men compared with women, there was no statistical difference in their topographic distribution. The proportion of distal, proximal, and synchronous neoplasms in the male and female groups were not statistically significantly different (Table 8). The prevalence of neoplasm in the proximal colon increased with the age of the subjects (P ! .001) (Fig. 2). The prevalence of advanced neoplasm in the proximal colon also tended to increase with age, although the difference did not reach statistical significance (P Z .245) (Fig. 2). Of the patients with colorectal neoplasm, the proportion of patients with colorectal neoplasm in the proximal colon or in both the proximal and the distal colon increased as the age of patients increased (P Z .034) (Fig. 3). www.giejournal.org
TABLE 8. Topographic distribution of colorectal neoplasms in men and women Men, no. (%) Women no. (%) (n Z 471) (n Z 389) Overall neoplasm
P
106 (22.5)
62 (15.9)
.016
Distal*
45 (42.5)
31 (50.0)
.34
Proximal*
43 (40.6)
23 (37.1)
.66
Synchronous*
18 (16.8)
8 (12.9)
.48
Advanced neoplasm
28 (5.9)
11 (2.8)
.029
Distaly
13 (46.4)
6 (54.5)
.65
Proximaly
13 (46.4)
4 (36.4)
.73
2 (7.2)
1 (9.1)
.999
Synchronousy
*The 23 table for topographic distribution of overall neoplasm (distal, proximal, and synchronous) and different sexes showed an insignificant difference (P Z .6). yThe 23 table for topographic distribution of advanced neoplasm (distal, proximal, and synchronous) and different sexes showed an insignificant difference (P Z .85).
DISCUSSION In the present study, overall colorectal neoplasm and advanced neoplasm among asymptomatic Asians were found in 18.5% and 4.5% of the studied subjects, respectively. These rates appear to be numerically lower than those observed in Western studies, in which the prevalence of overall colorectal neoplasm ranged from 20.4% to 37.5% and that of advanced neoplasm ranged from 4.9% to 10.5%.8,11,12 However, the figures of colonic neoplasms and advanced neoplasms are very compatible with a recent study that compared an Asian population in Taiwan (14.7% and 4%, respectively) with a Western population in Seattle (20.7% and 4.9%, respectively).22 Although genetic and environmental factors may contribute to the discrepant results,23,24 differences in subject enrollment should be noted. In Lieberman’s study, the cohort predominantly included men (96.8% of study population) with an age of 50 years or older (mean, 62.9 years).8 Volume 65, No. 7 : 2007 GASTROINTESTINAL ENDOSCOPY 1019
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Figure 2. Prevalence of colorectal neoplasm in the proximal colon according to age. The prevalence of proximal overall neoplasm increased with age (P ! .001). The prevalence of proximal advanced neoplasm also tended to increase with age (P Z .245).
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Figure 3. Proportion of patients with colorectal neoplasm in the proximal or in both the proximal and distal colon according to age.
Because male sex and advanced age are 2 well-known risk factors of colorectal neoplasm, the relatively high prevalence figures of Lieberman’s study were expected.7,9,11,25 On the contrary, when Imperiale et al10 recruited a cohort in which men comprised 61.0% of enrolled patients with a mean age of 44.8 years, they reported only 11.0% of colorectal neoplasm. In our present survey of asymptomatic Asian subjects, we enrolled 54.8% men, and the mean age was 54.4 years. Up to 34.3% of enrolled subjects in our study were less than 50 years old. When considering these results, along with the increase of colorectal cancer in Asian countries,16 we believe that the prevalence of colorectal neoplasm in asymptomatic Asian population, at least in the more affluent societies, is actually very similar to that of Western population. Asia is the most densely populated continent in the world. With the existing infrastructure and health care system, it would be very difficult, if not impossible, to perform colorectal-cancer screening for the whole population older than 50 years of age. Japan and Korea, being the most affluent societies in this region, may be the exceptions. It, therefore, is very important to identify the high-risk populations before we can consider any population-based screening for colorectal cancer. Our findings show that male sex, old age, and a family history of colorectal cancer were identified as risk factors for advanced neoplasm in the colon. This is consistent with reports from the West.7,9,11,25 In the present study, the odds ratio (OR) of men to women for advanced neoplasm was 2.4, and the OR of those with an age of 50 years or older to those less than 50 years was 3.7. This is echoed by a recent study from Taiwan, which also reported an increased prevalence of colorectal neoplasm in men and in older subjects.26 Results from the current study also showed that, with the advancing age, it is more likely to find proximal lesions. In this study, Korean and Japanese were found to have the highest incidence of
colonic neoplasms (Table 4). However, the study is limited by a large imbalance of input from each participating center, and we would be very cautious of putting too much weight on the interpretation of differences among different ethnic groups. Nevertheless, this would be an important area for further studies with a large sample population from each country. Although a 2- to 3-fold increase in the risk of colorectal cancer was reported in subjects with first-degree family history of colorectal cancer,27-29 few studies addressed the risk of finding advanced colorectal adenoma in those with a family history of colorectal cancer. Within their cohort, Lieberman et al8 demonstrated a 1.5-fold age-adjusted increased risk of advanced colorectal neoplasm in subjects with a family history of colorectal cancer. In France, Pariente et al30 observed an increased risk of adenoma (OR 1.5, 95% CI 1.0-2.4) and large adenoma (OR 2.5, 95% CI 1.1-5.4) in subjects with a family history of colorectal cancer. In this Asian cohort, the OR for colorectal neoplasm for those with a family history of colorectal cancer relative to those without was 2.5 (95% CI 1.5-4.2) and that for advanced neoplasm was 3.2 (95% CI 1.3-7.7). This association seemed to be stronger than what has been reported so far. Because a family history in the first-degree relatives constitutes an important risk, screening for colorectal cancer and advanced neoplasm should probably be targeted to this group. The findings regarding distal colon were suggested as a useful predictor for detecting proximal colonic neoplasm. Compared with Western patients, Asian patients were found to have a higher proportion of distal neoplasia.22 Most studies indicate that the presence of distal advanced neoplasm is a significant predictor for proximal advanced neoplasm.8,9,31 However, there has been controversy about the importance of detecting hyperplastic polyps and nonadvanced neoplasms in the distal colon.31,32 In our cohort, about 40% of adenomas and up to 43% of advanced neoplasm were found only in the proximal colon. Among those who had no abnormality in the distal colon, 8.7%
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had proximal neoplasm and 1.8% had advanced neoplasm. When assessing the risk of finding a proximal advanced lesion based on findings in the distal colon, only advanced neoplasm but not hyperplastic polyp or nonadvanced adenoma in the distal colon had significant predictive value. By putting these together, the current study suggests that if one finds an advanced neoplasm in the distal colon in sigmoidoscopy, there is a strong indication for a complete colonoscopy. However, reliance on findings in sigmoidoscopy may lead to missing the diagnosis of advanced neoplasm in up to 40% of cases. These findings are similar to those reported from Hong Kong and strongly support the need for a colonoscopy as a primary screening modality.33 A benefit may be larger in subjects with a family history of colorectal cancer, because this group was an independent risk factor for the presence of proximal advanced neoplasm of those without any distal neoplasm.34 Our study had several limitations. First and foremost, it is possible that there was selection bias in this cohort. This study recruited asymptomatic subjects who ‘‘self referred’’ for colonoscopic screening. In the Western literature, the screening populations usually refer to asymptomatic and average-risk individuals. In the present study, subjects are likely to be the more health-conscious group and, hence, not the ideal representation of the general population. The fact that 12.7% had a first-degree family history of colorectal cancer in this cohort also suggests that they were not ‘‘average-risk’’ individuals. Most countries in Asia, with the exception of Taiwan, Japan, and Korea do not have national health insurance coverage. The health care system and the health insurance policy of each participating country may also have preselected the group of higher socioeconomic status to be enrolled in this study. Second, the number of enrolled subjects was relatively small. In addition, the distribution of ethnic groups was not even: Korean and Chinese people represented more than 80% of the study population, whereas Japanese, Indian, and Indonesian people were underrepresented. This discrepancy reflects the clinical workload and the type of practice in the participating centers. The Asia Pacific Working Group resolved to continue recruiting more asymptomatic individuals in each country to substantiate the findings in this study. Recommendations on colon-cancer screening would not be possible without robust data supported by a larger sample size in our future studies. Finally, as in any multicenter study, interobserver variation among colonoscopists may affect the findings. We cannot exclude the possibility that pathologists in the local centers may also vary in their interpretation of the severity of dysplasia and, hence, the diagnosis of advanced lesions. Given these limitations and constraint, however, this study represents the first consorted effort in Asia to investigate the characteristics of colorectal neoplasm in a prospective manner. In conclusion, colorectal adenoma and advanced neoplasm are common in asymptomatic Asian subjects. Male sex, advancing age, and a family history of colorectal www.giejournal.org
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cancer are the major predictive factors for detecting colonic advanced neoplasm. Although finding distal advanced neoplasm predicts the diagnosis of proximal advanced neoplasm, two thirds of patients with proximal advanced neoplasm will be missed if only the distal colon is examined. Colonoscopic screening of high-risk asymptomatic individuals should be considered in Asia. DISCLOSURES The authors have no disclosures to make.
REFERENCES 1. Jemal A, Tiwari RC, Murray T, et al. Cancer statistics, 2004. CA Cancer J Clin 2004;54:8-29. 2. Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993;328:1365-71; erratum in: N Engl J Med 1993;329:672. 3. Hardcastle JD, Chamberlain JO, Robinson MH, et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet 1996;348:1472-7. 4. Kronborg O, Fenger C, Olsen J, et al. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet 1996;348: 1467-71. 5. Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med 1993;329:1977-81. 6. Citarda F, Tomaselli G, Capocaccia R, et al. Efficacy in standard clinical practice of colonoscopic polypectomy in reducing colorectal cancer incidence. Gut 2001;48:812-5. 7. Rex DK, Lehman GA, Ulbright TM, et al. Colonic neoplasia in asymptomatic persons with negative fecal occult blood tests: influence of age, gender, and family history. Am J Gastroenterol 1993;88:825-31. 8. Lieberman DA, Weiss DG, Bond JH, et al. Use of colonoscopy to screen asymptomatic adults for colorectal cancer. Veterans Affairs Cooperative Study Group 380. N Engl J Med 2000;343:162-8; erratum in: N Engl J Med 2000;343:1204. 9. Imperiale TF, Wagner DR, Lin CY, et al. Risk of advanced proximal neoplasms in asymptomatic adults according to the distal colorectal findings. N Engl J Med 2000;343:169-74. 10. Imperiale TF, Wagner DR, Lin CY, et al. Results of screening colonoscopy among persons 40 to 49 years of age. N Engl J Med 2002; 346:1781-5. 11. Betes M, Munoz-Navas MA, Duque JM, et al. Use of colonoscopy as a primary screening test for colorectal cancer in average risk people. Am J Gastroenterol 2003;98:2648-54. 12. Schoenfeld P, Cash B, Flood A, et al. Colonoscopic screening of average-risk women for colorectal neoplasia. N Engl J Med 2005;352: 2061-8. 13. Winawer S, Fletcher R, Rex D, et al. Colorectal cancer screening and surveillance: clinical guidelines and rationaledupdate based on new evidence. Gastroenterology 2003;124:544-60. 14. Rhodes JM. Colorectal cancer screening in the UK: joint position statement by the British Society of Gastroenterology, the Royal College of Physicians, and the Association of Coloproctology of Great Britain and Ireland. Gut 2000;46:746-8. 15. WGO-OMGE position statement: colorectal cancer screening and surveillance [accessed 2006 Jan 13]. Available from: URL:http:// omge.org/globalguidelines/statement03/statement3.htm. 16. Sung JJ, Lau JY, Goh KL, et al. Increasing incidence of colorectal cancer in Asia: implications for screening. Lancet Oncol 2005;6:871-6.
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Colorectal neoplasm in asymptomatic Asians 17. Tamura K, Ishiguro S, Munakata A, et al. Annual changes in colorectal carcinoma incidence in Japan. Analysis of survey data on incidence in Aomori Prefecture. Cancer 1996;78:1187-94. 18. Hong Kong Cancer Registry, Hospital Authority of Hong Kong Special Administrative Region [accessed 2005 Nov]. Available from: URL: http://www3.ha.org.hk/cancereg/. 19. Bae JM, Jung KW, Won YJ. Estimation of cancer deaths in Korea for the upcoming years. J Korean Med Sci 2002;17:611-5. 20. Hamilton SR, Kudo S, Riboli E, et al. Tumors of the colon and rectum. In: Hamilton SR, Aaltonen LA, editors. World Health Organization classifications of tumors: pathology and genetics of tumors of the digestive system. Lyon (France): IARC; 2000. 21. World Medical Association Declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. JAMA 1997;277:925-6. 22. Soon MS, Kozarek RA, Ayub K, et al. Screening colonoscopy in Chinese and Western patients: a comparative study. Am J Gastroenterol 2005;100:2749-55. 23. Rex DK, Rawl SM, Rabeneck L, et al. Colorectal cancer in African Americans. Rev Gastroenterol Disord 2004;4:60-5. 24. Flood DM, Weiss NS, Cook LS, et al. Colorectal cancer incidence in Asian migrants to the United States and their descendants. Cancer Causes Control 2000;11:403-11. 25. Imperiale TF, Wagner DR, Lin CY, et al. Using risk for advanced proximal colonic neoplasia to tailor endoscopic screening for colorectal cancer. Ann Intern Med 2003;139:959-65. 26. Chiu HM, Wang HP, Lee YC, et al. A prospective study of the frequency and the topographical distribution of colon neoplasia in asymptomatic average-risk Chinese adults as determined by colonoscopic screening. Gastrointest Endosc 2005;61:547-53. 27. Negri E, Braga C, La Vecchia C, et al. Family history of cancer and risk of colorectal cancer in Italy. Br J Cancer 1998;77:174-9. 28. Hemminki K, Li X. Familial colorectal adenocarcinoma from the Swedish Family Cancer Database. Int J Cancer 2001;94:743-8.
Byeon et al 29. Johns LE, Houlston RS. A systematic review and meta-analysis of familial colorectal cancer risk. Am J Gastroenterol 2001;96:2992-3003. 30. Pariente A, Milan C, Lafon J, et al. Colonoscopic screening in first-degree relatives of patients with ‘sporadic’ colorectal cancer: a case-control study. The Association Nationale des Gastroenterologues des Hopitaux and Registre Bourguignon des Cancers Digestifs (INSERM CRI 9505). Gastroenterology 1998;115:7-12. 31. Levin TR, Palitz A, Grossman S, et al. Predicting advanced proximal colonic neoplasia with screening sigmoidoscopy. JAMA 1999;281:1611-7. 32. Wallace MB, Kemp JA, Trnka YM, et al. Is colonoscopy indicated for small adenomas found by screening flexible sigmoidoscopy? Ann Intern Med 1998;129:273-8. 33. Sung JJ, Chan FK, Leung WK, et al. Screening for colorectal cancer in Chinese: comparison of fecal occult blood test, flexible sigmoidoscopy, and colonoscopy. Gastroenterology 2003;124:608-14. 34. Anderson JC, Alpern Z, Messina CR, et al. Predictors of proximal neoplasia in patients without distal adenomatous pathology. Am J Gastroenterol 2004;99:472-7.
Received November 18, 2006. Accepted December 31, 2006. Current affiliations: Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center (J-S.B., S-K.Y.), Department of Internal Medicine, Yonsei University College of Medicine (T.I.K., W.H.K.), Seoul, Korea, the Asia Pacific Working Group for Colorectal Cancer (J.Y.W.L., W-K.L., R.F., G.K.M., M.A., I.H., J.S., K-G.Y., D-C.W., M.H.C., P.K., J.J.Y.S.). This study was sponsored by the Asia Pacific Society of Digestive Endoscopy. Reprint requests: Joseph Sung, MD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
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1022 GASTROINTESTINAL ENDOSCOPY Volume 65, No. 7 : 2007
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Colorectal neoplasm in asymptomatic Asians: a prospective multinational multicenter colonoscopy survey Jeong-Sik Byeon, MD, Suk-Kyun Yang, MD, Tae Il Kim, MD, Won Ho Kim, MD, James Y. W. Lau, MD, Wai-Keung Leung, MD, Rikiya Fujita, MD, Govind K. Makharia, MD, Murdan Abdullah, MD, Ida Hilmi, MD, Jose Sollano, MD, Khay-Guan Yeoh, MD, Deng-Chyang Wu, MD, Min Hu Chen, MD, Pradermchai Kongkam, MD, Joseph J. Y. Sung, MD, for the Asia Pacific Working Group for Colorectal Cancer Seoul, Korea
Background: Colorectal neoplasm is rapidly increasing in Asia, but a guideline for screening is not available. Objective: To evaluate the characteristics of colorectal neoplasm in asymptomatic Asian subjects. Design: Prospective cohort study. Setting: Multinational multicenters, including both primary and referral centers in Asia. Patients: A total of 860 consecutive asymptomatic adults undergoing screening colonoscopy in 11 Asian cities from July 2004 to December 2004. Patients under 16 years old; those patients with a colorectal resection history, colonoscopies, or barium enema within 5 years; symptoms suggestive of colorectal diseases; and those who had undergone surveillance colonoscopy were excluded. Main Outcome Measurements: The incidence and distribution of colorectal neoplasm and advanced neoplasm. Results: The mean age (SD) was 54.4 11.6 years; 471 were men (54.8%). The prevalence of colorectal neoplasm and advanced neoplasm was 18.5% and 4.5%, respectively. Male sex, advancing age, and a family history of colorectal cancer were risk factors for advanced neoplasm. Of the 168 patients with colorectal neoplasm, 76 had distal neoplasm only (45.2%), 66 had proximal neoplasm only (39.3%), and 26 had both proximal and distal neoplasms (15.5%). Although the presence of distal advanced neoplasm was a significant risk factor for proximal advanced neoplasm, 14 of the 758 subjects without distal neoplasm had proximal advanced neoplasm (1.8%). Limitations: The small number of enrolled subjects, especially from certain ethnic groups. Conclusions: The overall prevalence of advanced colorectal neoplasm in asymptomatic Asians is comparable with the West. Male sex, advancing age, and a family history of colorectal cancer were associated with a higher risk of advanced neoplasm. (Gastrointest Endosc 2007;65:1015-22.)
Colorectal cancer is one of the most common malignancies in Western countries. According to the incidence and mortality data from the National Center for Health Statistics and the National Cancer Institute in the United States, colorectal cancer was estimated to comprise 10.7% of new cancer cases and was the second leading cause of cancer death in the United States in 2004.1 Efforts have been made to reduce mortality associated with this Copyright ª 2007 by the American Society for Gastrointestinal Endoscopy 0016-5107/$32.00 doi:10.1016/j.gie.2006.12.065
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important malignancy. Fecal occult blood screening for colorectal cancer has been shown to decrease the mortality from colorectal cancer.2-4 Colonoscopic polypectomy has been demonstrated to decrease the incidence of colorectal cancer in a large cohort study, as well as in clinical practice.5,6 Based on these findings and other studies about the prevalence of colorectal neoplasm,7-12 national and international professional bodies, including the American Gastroenterological Association, the British Society of Gastroenterology, and the World Gastroenterology Organization, established guidelines for colorectal cancer screening and surveillance.13-15 Volume 65, No. 7 : 2007 GASTROINTESTINAL ENDOSCOPY 1015
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In Asia, cancers of the stomach and the liver have traditionally predominated cancer incidence, and colorectal cancer was not common. During the past few decades, there has been a remarkable increase of colorectal cancer in Asian countries.16 In Aomori Prefecture in Japan, the age-adjusted incidences for colorectal cancer were 12.6 and 8.7 per 100,000 population for men and women, respectively, in 1974, and increased to 42.5 and 25.6 per 100,000 population, respectively, in 1991.17 In Hong Kong, China, the incidence of colorectal cancer in men increased from 40.0 per 100,000 in 1992 to 60.0 per 100,000 in 2002.18 Based on cancer death statistics reported by the South Korea National Statistical Office from 1983 to 2000 and projecting cancer mortality between 2001 and 2005, the National Cancer Center of Korea reported a 35% increase in colorectal cancer mortality in both men and women.19 Despite the rapid emergence of colorectal cancer in Asia, the epidemiology of this disease in this region remains unclear. We conducted a prospective, multinational, multicenter colonoscopy survey to assess the characteristics of colorectal neoplasm in Asia. The purpose of this study was to investigate the occurrence and location of colorectal neoplasm in asymptomatic Asian subjects. We also aimed to explore the risk factors for colorectal neoplasm, including the risk of advanced neoplasm in the proximal colon according to the findings in the distal colon.
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Capsule Summary What is already known on this topic d
Cancers of the stomach and the liver traditionally have been predominant in Asia, but a remarkable increase in the incidence of colorectal cancer has been seen in the last decades.
What this study adds to our knowledge d
In a prospective study of 860 consecutive asymptomatic Asian adults undergoing screening colonoscopy, the prevalence of colorectal neoplasm and advanced neoplasm was 18.5% and 4.5%, respectively, with male sex, advancing age, and family history of colorectal cancer being risk factors for advanced neoplasm.
pain that required medical evaluation, and those with a history of colorectal disease, such as polyp, cancer, or inflammatory bowel disease, were also excluded.
Study protocol
This was a pilot study to investigate the findings of colonoscopy in asymptomatic Asian subjects. We set out to conduct a prospective, multinational, multicenter study by using a database designed by the Asia Pacific Working Group for Colorectal Cancer. We aimed to include consecutive asymptomatic subjects above the age of 16 years, who were undergoing colonoscopy as a screening procedure referred to 17 centers from 11 Asian cities (Bangkok, Guangzhou, Hong Kong, Jakarta, Kuala Lumpur, Manila, New Delhi, Seoul, Singapore, Taipei, and Tokyo) over a period of 6 months. Because there is no national guideline for colorectal cancer screening in Asian countries, asymptomatic subjects who came forward requesting colonoscopy were recommended by their family members or primary care physicians. Self-referred young subjects (less than the age of 50 years) usually had a family history of colorectal cancer. We excluded subjects who had undergone colorectal imaging (including sigmoidoscopy, colonoscopy, or barium enema) within the previous 5 years, those with a history of colorectal surgery, and those colonoscopic examinations that failed to reach the cecum. Subjects with symptoms of lower-GI tract disease, including rectal bleeding, a change in bowel habits, or lower abdominal
Eligible persons who provided informed consent completed detailed questionnaires that covered a personal history of colorectal diseases; colorectal examination; and colorectal surgery; and a family history of cancer, including colorectal cancer. All colonoscopies were performed at the participating centers by experienced colonoscopists. During the examination, all polypoid lesions were documented for location and size. The distal colon was defined as 40 cm from the anal verge. The proximal colon was defined as the splenic flexure and the more proximal portions of the colon. The size of each polyp was estimated with the use of an 8-mmdiameter open-biopsy forceps. All the polyps were biopsied or polypectomized, and the obtained specimens were sent to local pathology laboratories at the participating centers for the histologic evaluation. Colorectal neoplasm was classified according to World Health Organization criteria.20 Advanced colorectal neoplasm was defined as an adenoma with a diameter of 10 mm or more, a villous adenoma (ie, at least 25% villous), an adenoma with high-grade dysplasia, or invasive cancer. Invasive cancer was defined as the invasion of malignant cells beyond the muscularis mucosa. Patients were classified on the basis of their most advanced lesion to determine the prevalence of pathologic features. For example, a patient with a villous adenoma and a tubular adenoma was classified as having a villous adenoma. All colonoscopy and histology results of included subjects were registered into a centralized database. The prevalence of all neoplasms and advanced colorectal neoplasm was determined. Risk factors for the presence of colorectal neoplasm were evaluated in terms of sex, age, family history of colorectal cancer, and ethnicity. The distribution
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PATIENTS AND METHODS Subjects
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TABLE 1. Age distribution of the 860 subjects
TABLE 2. Ethnic distribution of the 860 subjects
Age group, y
No. (%)
Ethnic group
20-39
86 (10.0)
Korean
382 (44.4)
40-49
209 (24.3)
Chinese
355 (41.3)
50-59
271 (31.5)
Filipino
57 (6.6)
60-69
214 (24.9)
Thai
22 (2.6)
70-79
64 (7.4)
Japanese
13 (1.5)
80-90
16 (1.9)
White
12 (1.4)
Indian
11 (1.3)
Malay
5 (0.6)
Indonesian
3 (0.3)
of colorectal neoplasm was also analyzed, and the risk of proximal neoplasm associated with distal colorectal lesions was determined. This study was carried out in accordance with the Helsinki Declaration.21
Statistical analysis Statistical analyses were performed with SPSS (version 11.5; SPSS Inc, Chicago, Ill). Continuous data about subject characteristics and outcomes were compared with the use of the Student t test and the Mann-Whitney U test. The Pearson c2 test or the Fisher exact test was used for the proportion analysis of categorical data. We calculated the relative risk and 95% confidence intervals (CI) in the analysis of the risk of colorectal neoplasm. A multiple logistic regression model was used to analyze the risk factors for colorectal neoplasm. All P values were 2-tailed, and a P value less than .05 was considered statistically significant.
RESULTS Characteristics of study population From July 2004 to December 2004, a total of 7290 subjects underwent a colonoscopy in the 17 participating centers. There were 860 asymptomatic adults who underwent colonoscopy and were analyzed in this study. Among them, 471 were men (54.8%). The mean age (SD) was 54.4 11.6 years (range, 20-90 years). In this cohort, 565 subjects (65.7%) were 50 years or older. There were 9 ethnic groups (Chinese, Indian, Indonesian, Japanese, Korean, Malay, Filipino, Thai, and white); Korean and Chinese were the 2 most common ethnic groups in this cohort. A total of 109 subjects (12.7%) had a positive history of colorectal cancer in their first-degree relatives. The distributions of age and ethnic groups of the study population are shown in Tables 1 and 2.
Prevalence of colorectal neoplasm Among the 860 asymptomatic subjects, 168 (18.5%) were found to have colorectal neoplasm. Advanced colowww.giejournal.org
No. (%)
rectal neoplasm was detected in 39 patients (4.5%), and invasive cancers were found in 9 patients (1.0%). The prevalence of colorectal neoplasm was higher in men (106/471 [22.5%]) than in women (62/389 [15.9%]) (P Z .016). Colorectal neoplasm was detected in 135 of 565 subjects (23.9%) with an age of 50 years or older, and the prevalence was significantly higher than that of those less than 50 years (33/295 [11.2%]; P ! .001). The prevalence of colorectal neoplasm increased as the age of subjects increased (P ! .001) (Fig. 1). The prevalence of colorectal neoplasm tended to be higher in the subjects with a positive history of colorectal cancer in their firstdegree relatives than in those without a family history of colorectal cancer: 27/109 (24.8%) versus 141/751 (18.8%), respectively. However, the difference did not reach statistical significance in univariate analysis (P Z .140). The prevalence of advanced colorectal neoplasm demonstrated similar features with that of overall neoplasms in terms of sex, age, and family history of colorectal cancer. The characteristics of prevalence of colorectal neoplasm are summarized in Table 3. With multivariate analysis, by using logistic regression model, male sex, advancing age, a positive history of colorectal cancer in the first-degree relatives, and the ethnicity of Korean or Japanese stand out to be significant risk factors for colorectal neoplasm (Table 4). Male sex, advancing age, and a positive history of colorectal cancer in the firstdegree relatives also increased the risk of advanced colorectal neoplasm (Table 5).
Topographical distribution of colorectal neoplasm Of the 168 patients with colorectal neoplasm, 76 (45.2%) had their neoplasm only in the distal colon. Sixty-six patients (39.3%) had neoplasm found only in the proximal colon, and 26 (15.5%) had their neoplasm found in both the proximal and the distal colon. Of the 39 patients with advanced colorectal neoplasm, 19 Volume 65, No. 7 : 2007 GASTROINTESTINAL ENDOSCOPY 1017
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TABLE 4. Risk factors for colorectal neoplasm
Male sex Age
OR (95% CI)
P
1.5 (1.1-2.2)
.019
1.05 (1.03-1.07) .001
Family history of colorectal cancer*
2.5 (1.5-4.2)
Ethnicity Chinese
Figure 1. Prevalence of overall colorectal neoplasm according to age. As the age increased, the prevalence of colorectal neoplasm increased (P ! .001).
TABLE 3. Patients with colorectal neoplasm stratified by sex, age, and family history of colorectal cancer (CRC)
Overall neoplasm Prevalence, no. (%)
P
106 (22.5)
Female (n Z 389)
62 (15.9)
.016
.019
Korean
2.0 (1.3-2.9)
.001
Filipino
0.3 (0.1-1.0)
.056
Indian
0.3 (0.0-2.4)
.250
Indonesian
0.0 (0.0, d)
.999
Malay
0.0 (0.0, d)
.999
Thai
0.2 (0.0-1.3)
.084
White
1.9 (0.5-7.4)
.371
*A family history of colorectal cancer was defined as 1 or more affected first-degree relatives.
Advanced neoplasm Prevalence, no. (%)
P
28 (5.9)
.029
TABLE 5. Risk factors for advanced colorectal neoplasm
Male sex Age
11 (2.8)
Age 33 (11.2)
R50 y (n Z 565)
135 (23.9)
!.001
6 (2.0)
.001
33 (5.8)
First-degree family history of colorectal cancer* 27 (24.8)
Absent (n Z 751)
141 (18.8)
.140
8 (7.3)
OR (95% CI)
P
2.3 (1.1-4.8)
.023
1.04 (1.01-1.08)
.005
3.2 (1.3-7.7)
.009
Ethnicity Chinese
Present (n Z 109)
Reference 4.2 (1.3-13.9)
Family history of colorectal cancer*
!50 y (n Z 295)
.001
Japanese
Sex Male (n Z 471)
.001
.807 Reference
Japanese
2.7 (0.3-23.3)
.364
Korean
1.9 (0.9-4.0)
.069
Filipino
0.6 (0.1-4.7)
.613
Indian
1.7 (0.2-15.4)
.647
Indonesian
0.0 (0.0)
.999
Malay
0.0 (0.0)
.999
Thai
0.0 (0.0)
.998
White
0.0 (0.0)
.999
.139
31 (4.1)
*A family history of colorectal cancer was defined as 1 or more affected first-degree relatives.
*A family history of colorectal cancer was defined as 1 or more affected first-degree relatives.
(48.7%) had their advanced neoplasm in the distal colon. Seventeen patients (43.6%) had advanced neoplasm found only in the proximal colon, and 3 (7.7%) had their advanced neoplasm in both the proximal and the distal colon.
Of the 102 patients with distal neoplasm, 26 (25.5%) had proximal neoplasm as well. However, 66 of 758 subjects (8.7%) without colorectal neoplasm in the distal colon had colonic neoplasm in the proximal colon (P ! .001) and 14 (1.8%) had advanced neoplasm in the
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TABLE 6. Risk of advanced neoplasm in the proximal colon according to the colonoscopic findings in the distal colon Colonoscopic finding in distal colon
Total no. patients
No. patients with proximal advanced neoplasm
Adjusted relative risk (95% CI)*
720
13
1.0
Hyperplastic polyp
38
1
1.3 (0.2-10.4)
Nonadvanced neoplasm
80
3
1.7 (0.5-6.3)
Advanced neoplasm
22
3
6.3 (1.6-25.4)
No polyp
*The relative risk was adjusted for age and sex. The group of patients with no polyp in the distal colon was the reference group.
TABLE 7. Risk factors for proximal advanced neoplasm in 720 subjects without any polyps in the distal colon OR (95% CI)
P
Male sex
3.5 (0.9-13.4)
.071
Age R 50 y
3.1 (0.7-12.8)
.122
Family history of colorectal cancer*
6.0 (1.3-26.6)
.019
Ethnicity
d
.600
*A family history of colorectal cancer was defined as 1 or more affected first-degree relatives.
proximal colon. When the risk of proximal advanced neoplasm was analyzed according to the colonoscopy findings in the distal colon, the presence of distal advanced neoplasm was the only significant risk factor for proximal advanced neoplasm (Table 6). A positive history of colorectal cancer in first-degree relatives significantly increased the risk of proximal advanced neoplasm in 720 subjects without any distal polyp (Table 7). Of the 20 patients with proximal advanced neoplasm, only 7 (35.0%) had 1 or more colorectal neoplasm in the distal colon. Although the prevalence of all colorectal neoplasm (22.5% vs 15.9%, P Z.016) and advanced neoplasm (5.9% vs 2.8%, P Z.029) were significantly higher with men compared with women, there was no statistical difference in their topographic distribution. The proportion of distal, proximal, and synchronous neoplasms in the male and female groups were not statistically significantly different (Table 8). The prevalence of neoplasm in the proximal colon increased with the age of the subjects (P ! .001) (Fig. 2). The prevalence of advanced neoplasm in the proximal colon also tended to increase with age, although the difference did not reach statistical significance (P Z .245) (Fig. 2). Of the patients with colorectal neoplasm, the proportion of patients with colorectal neoplasm in the proximal colon or in both the proximal and the distal colon increased as the age of patients increased (P Z .034) (Fig. 3). www.giejournal.org
TABLE 8. Topographic distribution of colorectal neoplasms in men and women Men, no. (%) Women no. (%) (n Z 471) (n Z 389) Overall neoplasm
P
106 (22.5)
62 (15.9)
.016
Distal*
45 (42.5)
31 (50.0)
.34
Proximal*
43 (40.6)
23 (37.1)
.66
Synchronous*
18 (16.8)
8 (12.9)
.48
Advanced neoplasm
28 (5.9)
11 (2.8)
.029
Distaly
13 (46.4)
6 (54.5)
.65
Proximaly
13 (46.4)
4 (36.4)
.73
2 (7.2)
1 (9.1)
.999
Synchronousy
*The 23 table for topographic distribution of overall neoplasm (distal, proximal, and synchronous) and different sexes showed an insignificant difference (P Z .6). yThe 23 table for topographic distribution of advanced neoplasm (distal, proximal, and synchronous) and different sexes showed an insignificant difference (P Z .85).
DISCUSSION In the present study, overall colorectal neoplasm and advanced neoplasm among asymptomatic Asians were found in 18.5% and 4.5% of the studied subjects, respectively. These rates appear to be numerically lower than those observed in Western studies, in which the prevalence of overall colorectal neoplasm ranged from 20.4% to 37.5% and that of advanced neoplasm ranged from 4.9% to 10.5%.8,11,12 However, the figures of colonic neoplasms and advanced neoplasms are very compatible with a recent study that compared an Asian population in Taiwan (14.7% and 4%, respectively) with a Western population in Seattle (20.7% and 4.9%, respectively).22 Although genetic and environmental factors may contribute to the discrepant results,23,24 differences in subject enrollment should be noted. In Lieberman’s study, the cohort predominantly included men (96.8% of study population) with an age of 50 years or older (mean, 62.9 years).8 Volume 65, No. 7 : 2007 GASTROINTESTINAL ENDOSCOPY 1019
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Figure 2. Prevalence of colorectal neoplasm in the proximal colon according to age. The prevalence of proximal overall neoplasm increased with age (P ! .001). The prevalence of proximal advanced neoplasm also tended to increase with age (P Z .245).
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Figure 3. Proportion of patients with colorectal neoplasm in the proximal or in both the proximal and distal colon according to age.
Because male sex and advanced age are 2 well-known risk factors of colorectal neoplasm, the relatively high prevalence figures of Lieberman’s study were expected.7,9,11,25 On the contrary, when Imperiale et al10 recruited a cohort in which men comprised 61.0% of enrolled patients with a mean age of 44.8 years, they reported only 11.0% of colorectal neoplasm. In our present survey of asymptomatic Asian subjects, we enrolled 54.8% men, and the mean age was 54.4 years. Up to 34.3% of enrolled subjects in our study were less than 50 years old. When considering these results, along with the increase of colorectal cancer in Asian countries,16 we believe that the prevalence of colorectal neoplasm in asymptomatic Asian population, at least in the more affluent societies, is actually very similar to that of Western population. Asia is the most densely populated continent in the world. With the existing infrastructure and health care system, it would be very difficult, if not impossible, to perform colorectal-cancer screening for the whole population older than 50 years of age. Japan and Korea, being the most affluent societies in this region, may be the exceptions. It, therefore, is very important to identify the high-risk populations before we can consider any population-based screening for colorectal cancer. Our findings show that male sex, old age, and a family history of colorectal cancer were identified as risk factors for advanced neoplasm in the colon. This is consistent with reports from the West.7,9,11,25 In the present study, the odds ratio (OR) of men to women for advanced neoplasm was 2.4, and the OR of those with an age of 50 years or older to those less than 50 years was 3.7. This is echoed by a recent study from Taiwan, which also reported an increased prevalence of colorectal neoplasm in men and in older subjects.26 Results from the current study also showed that, with the advancing age, it is more likely to find proximal lesions. In this study, Korean and Japanese were found to have the highest incidence of
colonic neoplasms (Table 4). However, the study is limited by a large imbalance of input from each participating center, and we would be very cautious of putting too much weight on the interpretation of differences among different ethnic groups. Nevertheless, this would be an important area for further studies with a large sample population from each country. Although a 2- to 3-fold increase in the risk of colorectal cancer was reported in subjects with first-degree family history of colorectal cancer,27-29 few studies addressed the risk of finding advanced colorectal adenoma in those with a family history of colorectal cancer. Within their cohort, Lieberman et al8 demonstrated a 1.5-fold age-adjusted increased risk of advanced colorectal neoplasm in subjects with a family history of colorectal cancer. In France, Pariente et al30 observed an increased risk of adenoma (OR 1.5, 95% CI 1.0-2.4) and large adenoma (OR 2.5, 95% CI 1.1-5.4) in subjects with a family history of colorectal cancer. In this Asian cohort, the OR for colorectal neoplasm for those with a family history of colorectal cancer relative to those without was 2.5 (95% CI 1.5-4.2) and that for advanced neoplasm was 3.2 (95% CI 1.3-7.7). This association seemed to be stronger than what has been reported so far. Because a family history in the first-degree relatives constitutes an important risk, screening for colorectal cancer and advanced neoplasm should probably be targeted to this group. The findings regarding distal colon were suggested as a useful predictor for detecting proximal colonic neoplasm. Compared with Western patients, Asian patients were found to have a higher proportion of distal neoplasia.22 Most studies indicate that the presence of distal advanced neoplasm is a significant predictor for proximal advanced neoplasm.8,9,31 However, there has been controversy about the importance of detecting hyperplastic polyps and nonadvanced neoplasms in the distal colon.31,32 In our cohort, about 40% of adenomas and up to 43% of advanced neoplasm were found only in the proximal colon. Among those who had no abnormality in the distal colon, 8.7%
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Byeon et al
had proximal neoplasm and 1.8% had advanced neoplasm. When assessing the risk of finding a proximal advanced lesion based on findings in the distal colon, only advanced neoplasm but not hyperplastic polyp or nonadvanced adenoma in the distal colon had significant predictive value. By putting these together, the current study suggests that if one finds an advanced neoplasm in the distal colon in sigmoidoscopy, there is a strong indication for a complete colonoscopy. However, reliance on findings in sigmoidoscopy may lead to missing the diagnosis of advanced neoplasm in up to 40% of cases. These findings are similar to those reported from Hong Kong and strongly support the need for a colonoscopy as a primary screening modality.33 A benefit may be larger in subjects with a family history of colorectal cancer, because this group was an independent risk factor for the presence of proximal advanced neoplasm of those without any distal neoplasm.34 Our study had several limitations. First and foremost, it is possible that there was selection bias in this cohort. This study recruited asymptomatic subjects who ‘‘self referred’’ for colonoscopic screening. In the Western literature, the screening populations usually refer to asymptomatic and average-risk individuals. In the present study, subjects are likely to be the more health-conscious group and, hence, not the ideal representation of the general population. The fact that 12.7% had a first-degree family history of colorectal cancer in this cohort also suggests that they were not ‘‘average-risk’’ individuals. Most countries in Asia, with the exception of Taiwan, Japan, and Korea do not have national health insurance coverage. The health care system and the health insurance policy of each participating country may also have preselected the group of higher socioeconomic status to be enrolled in this study. Second, the number of enrolled subjects was relatively small. In addition, the distribution of ethnic groups was not even: Korean and Chinese people represented more than 80% of the study population, whereas Japanese, Indian, and Indonesian people were underrepresented. This discrepancy reflects the clinical workload and the type of practice in the participating centers. The Asia Pacific Working Group resolved to continue recruiting more asymptomatic individuals in each country to substantiate the findings in this study. Recommendations on colon-cancer screening would not be possible without robust data supported by a larger sample size in our future studies. Finally, as in any multicenter study, interobserver variation among colonoscopists may affect the findings. We cannot exclude the possibility that pathologists in the local centers may also vary in their interpretation of the severity of dysplasia and, hence, the diagnosis of advanced lesions. Given these limitations and constraint, however, this study represents the first consorted effort in Asia to investigate the characteristics of colorectal neoplasm in a prospective manner. In conclusion, colorectal adenoma and advanced neoplasm are common in asymptomatic Asian subjects. Male sex, advancing age, and a family history of colorectal www.giejournal.org
Colorectal neoplasm in asymptomatic Asians
cancer are the major predictive factors for detecting colonic advanced neoplasm. Although finding distal advanced neoplasm predicts the diagnosis of proximal advanced neoplasm, two thirds of patients with proximal advanced neoplasm will be missed if only the distal colon is examined. Colonoscopic screening of high-risk asymptomatic individuals should be considered in Asia. DISCLOSURES The authors have no disclosures to make.
REFERENCES 1. Jemal A, Tiwari RC, Murray T, et al. Cancer statistics, 2004. CA Cancer J Clin 2004;54:8-29. 2. Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993;328:1365-71; erratum in: N Engl J Med 1993;329:672. 3. Hardcastle JD, Chamberlain JO, Robinson MH, et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet 1996;348:1472-7. 4. Kronborg O, Fenger C, Olsen J, et al. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet 1996;348: 1467-71. 5. Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med 1993;329:1977-81. 6. Citarda F, Tomaselli G, Capocaccia R, et al. Efficacy in standard clinical practice of colonoscopic polypectomy in reducing colorectal cancer incidence. Gut 2001;48:812-5. 7. Rex DK, Lehman GA, Ulbright TM, et al. Colonic neoplasia in asymptomatic persons with negative fecal occult blood tests: influence of age, gender, and family history. Am J Gastroenterol 1993;88:825-31. 8. Lieberman DA, Weiss DG, Bond JH, et al. Use of colonoscopy to screen asymptomatic adults for colorectal cancer. Veterans Affairs Cooperative Study Group 380. N Engl J Med 2000;343:162-8; erratum in: N Engl J Med 2000;343:1204. 9. Imperiale TF, Wagner DR, Lin CY, et al. Risk of advanced proximal neoplasms in asymptomatic adults according to the distal colorectal findings. N Engl J Med 2000;343:169-74. 10. Imperiale TF, Wagner DR, Lin CY, et al. Results of screening colonoscopy among persons 40 to 49 years of age. N Engl J Med 2002; 346:1781-5. 11. Betes M, Munoz-Navas MA, Duque JM, et al. Use of colonoscopy as a primary screening test for colorectal cancer in average risk people. Am J Gastroenterol 2003;98:2648-54. 12. Schoenfeld P, Cash B, Flood A, et al. Colonoscopic screening of average-risk women for colorectal neoplasia. N Engl J Med 2005;352: 2061-8. 13. Winawer S, Fletcher R, Rex D, et al. Colorectal cancer screening and surveillance: clinical guidelines and rationaledupdate based on new evidence. Gastroenterology 2003;124:544-60. 14. Rhodes JM. Colorectal cancer screening in the UK: joint position statement by the British Society of Gastroenterology, the Royal College of Physicians, and the Association of Coloproctology of Great Britain and Ireland. Gut 2000;46:746-8. 15. WGO-OMGE position statement: colorectal cancer screening and surveillance [accessed 2006 Jan 13]. Available from: URL:http:// omge.org/globalguidelines/statement03/statement3.htm. 16. Sung JJ, Lau JY, Goh KL, et al. Increasing incidence of colorectal cancer in Asia: implications for screening. Lancet Oncol 2005;6:871-6.
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Colorectal neoplasm in asymptomatic Asians 17. Tamura K, Ishiguro S, Munakata A, et al. Annual changes in colorectal carcinoma incidence in Japan. Analysis of survey data on incidence in Aomori Prefecture. Cancer 1996;78:1187-94. 18. Hong Kong Cancer Registry, Hospital Authority of Hong Kong Special Administrative Region [accessed 2005 Nov]. Available from: URL: http://www3.ha.org.hk/cancereg/. 19. Bae JM, Jung KW, Won YJ. Estimation of cancer deaths in Korea for the upcoming years. J Korean Med Sci 2002;17:611-5. 20. Hamilton SR, Kudo S, Riboli E, et al. Tumors of the colon and rectum. In: Hamilton SR, Aaltonen LA, editors. World Health Organization classifications of tumors: pathology and genetics of tumors of the digestive system. Lyon (France): IARC; 2000. 21. World Medical Association Declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. JAMA 1997;277:925-6. 22. Soon MS, Kozarek RA, Ayub K, et al. Screening colonoscopy in Chinese and Western patients: a comparative study. Am J Gastroenterol 2005;100:2749-55. 23. Rex DK, Rawl SM, Rabeneck L, et al. Colorectal cancer in African Americans. Rev Gastroenterol Disord 2004;4:60-5. 24. Flood DM, Weiss NS, Cook LS, et al. Colorectal cancer incidence in Asian migrants to the United States and their descendants. Cancer Causes Control 2000;11:403-11. 25. Imperiale TF, Wagner DR, Lin CY, et al. Using risk for advanced proximal colonic neoplasia to tailor endoscopic screening for colorectal cancer. Ann Intern Med 2003;139:959-65. 26. Chiu HM, Wang HP, Lee YC, et al. A prospective study of the frequency and the topographical distribution of colon neoplasia in asymptomatic average-risk Chinese adults as determined by colonoscopic screening. Gastrointest Endosc 2005;61:547-53. 27. Negri E, Braga C, La Vecchia C, et al. Family history of cancer and risk of colorectal cancer in Italy. Br J Cancer 1998;77:174-9. 28. Hemminki K, Li X. Familial colorectal adenocarcinoma from the Swedish Family Cancer Database. Int J Cancer 2001;94:743-8.
Byeon et al 29. Johns LE, Houlston RS. A systematic review and meta-analysis of familial colorectal cancer risk. Am J Gastroenterol 2001;96:2992-3003. 30. Pariente A, Milan C, Lafon J, et al. Colonoscopic screening in first-degree relatives of patients with ‘sporadic’ colorectal cancer: a case-control study. The Association Nationale des Gastroenterologues des Hopitaux and Registre Bourguignon des Cancers Digestifs (INSERM CRI 9505). Gastroenterology 1998;115:7-12. 31. Levin TR, Palitz A, Grossman S, et al. Predicting advanced proximal colonic neoplasia with screening sigmoidoscopy. JAMA 1999;281:1611-7. 32. Wallace MB, Kemp JA, Trnka YM, et al. Is colonoscopy indicated for small adenomas found by screening flexible sigmoidoscopy? Ann Intern Med 1998;129:273-8. 33. Sung JJ, Chan FK, Leung WK, et al. Screening for colorectal cancer in Chinese: comparison of fecal occult blood test, flexible sigmoidoscopy, and colonoscopy. Gastroenterology 2003;124:608-14. 34. Anderson JC, Alpern Z, Messina CR, et al. Predictors of proximal neoplasia in patients without distal adenomatous pathology. Am J Gastroenterol 2004;99:472-7.
Received November 18, 2006. Accepted December 31, 2006. Current affiliations: Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center (J-S.B., S-K.Y.), Department of Internal Medicine, Yonsei University College of Medicine (T.I.K., W.H.K.), Seoul, Korea, the Asia Pacific Working Group for Colorectal Cancer (J.Y.W.L., W-K.L., R.F., G.K.M., M.A., I.H., J.S., K-G.Y., D-C.W., M.H.C., P.K., J.J.Y.S.). This study was sponsored by the Asia Pacific Society of Digestive Endoscopy. Reprint requests: Joseph Sung, MD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
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