The Prevalence of Colorectal Adenomas in Asymptomatic Korean Men and Women

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1 Research Article Cancer Epidemiology, Biomarkers & Prevention The Prevalence of Colorectal Adenomas in Asymptomatic Korean Men and Women Moon Hee Yang 1, Sanjay Rampal 4,5, Jidong Sung 1,2, Yoon-Ho Choi 1,2, Hee Jung Son 1,2, Jun Haeng Lee 2, Young-Ho Kim 2, Dong Kyung Chang 2, Poong-Lyul Rhee 2, Jong Chul Rhee 2, Eliseo Guallar 5, and Juhee Cho 3,5 Abstract Background: Colorectal cancer incidence is rapidly rising in many Asian countries, with rates approaching those of Western countries. This study aimed to evaluate the prevalence and trends of colorectal adenomas by age, sex, and risk strata in asymptomatic Koreans. Methods: Cross-sectional study of 19,372 consecutive participants aged 20 to 79 years undergoing screening colonoscopy at the Center for Health Promotion of the Samsung Medical Center in Korea from January 2006 to June Results: Among participants at average risk, those without a history of colorectal polyps or a family history of colorectal cancer, the prevalence of colorectal adenomas and advanced adenomas were 34.5% and 3.1%, respectively, in men and 20.0% and 1.6%, respectively, in women. The prevalence of adenomas increased with age in both men and women, with a more marked increase for advanced adenoma. Participants with a family history of colorectal cancer or with a history of colorectal polyps had significantly higher prevalence of adenomas compared with participants of average risk (36.9% vs. 26.9%; age- and sex-adjusted prevalence ratio ¼ 1.16; 95% confidence interval, ). The prevalence of adenomas increased annually in both men and women. Conclusions: In this large study of asymptomatic Korean men and women participating in a colonoscopy screening program, the prevalence of colorectal adenomas was comparable and possibly higher than previously reported in Western countries. Impact: Cost-effectiveness studies investigating the optimal age for starting colonoscopy screening and etiological studies to identify the reasons for the increasing trend in colorectal adenomas in Koreans are needed. Cancer Epidemiol Biomarkers Prev; 23(3); Ó2014 AACR. Introduction Colorectal cancer incidence is rapidly rising in many Asian countries, with rates approaching those of Western countries (1). In Korea, the age-standardized incidence rate of colorectal cancer has increased from 20.4 to 36.2 per 100,000 between 1999 and 2009, with a higher increase in men (from 26.2 to 49.0 per 100,000 population) compared with women (16.4 to 25.9 per 100,000 population; ref. 2). The increasing incidence of colorectal cancer in recent Authors' Affiliations: 1 Center for Health Promotion, Samsung Medical Center; 2 Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine; and 3 Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea; 4 Department of Social and Preventive Medicine, Julius Centre University of Malaya, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; and 5 Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland M.H. Yang and S. Rampal contributed equally as first authors to this work. Corresponding Author: Juhee Cho, Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 50, Irwon-Dong Kangnam-Gu, Seoul , Korea. Phone: ; Fax: ; E mail: jcho@skku.edu doi: / EPI Ó2014 American Association for Cancer Research. years among Asian countries has been attributed to dietary changes, and higher prevalence of smoking, alcohol consumption, and sedentary lifestyle (3, 4). Indeed, in 2012 colorectal cancer accounted for 13.7% of new cancer cases and 11.2% of cancer deaths in Korea (5), highlighting the need for better colorectal cancer prevention and screening. Between 1998 and 2004, the average prevalence of colorectal adenomas and advanced adenomas were estimated at 30.2% and 4.1%, respectively, among averagerisk Koreans older than 50 (6). These participants had no symptoms of colorectal disease, no personal history of colorectal cancer, polyps, or inflammatory bowel disease, no colon examination within the last 10 years, no previous colonic surgery, and no family history of colorectal polyps. Similarly, a multicenter colonoscopy survey conducted in 2003 to 2004 among 11 university hospitals in Korea found prevalence rates of 33.3% and 2.2% for colorectal adenomas and advanced adenomas, respectively (7). Although it is assumed that the incidence of colorectal adenomas is increasing in proportion to colorectal cancer rates, there is limited data on recent adenoma trends in Korea (8). Our study aimed to evaluate theprevalenceandtrendsof colorectal adenomas by age, sex, and risk strata in asymptomatic Korean men 499

2 Yang et al. and women participating in a large colonoscopy screening program. Materials and Methods Study population The study population included 20,500 consecutive participants undergoing colonoscopy as part of routine health check-up examinations at the Center for Health Promotion of the Samsung Medical Center in Seoul, Korea, from January 2006 to June 2009 (9). If a participant had more than one colonoscopy during the study period, we included only the first colonoscopy. We excluded 1,128 participants with the following characteristics: nonscreening colonoscopy (N ¼ 817), incomplete colonoscopy, including insertion failures (N ¼ 173), age <20 years (N ¼ 4) or 80 years (N ¼ 11), history of colorectal surgery or colorectal cancer (N ¼ 49) or inflammatory bowel disease (N ¼ 27), and participants who were not Korean (N ¼ 47; Fig. 1). The final analysis included 19,372 participants (12,625 men and 6,747 women). The study protocol was approved by the Institutional Review Board of the Samsung Medical Center (Seoul, Korea). The requirement for informed consent was exempted by the Institutional Review Board of the Samsung Medical Center because the study was based on retrospective analyses of de-identified existing administrative and clinical data. Health examination All participants completed a questionnaire and received a detailed physical examination as part of the screening program. Body mass index (BMI) was calculated by dividing measured weight (kg) by measured height squared (m 2 ). Waist circumference was measured at the midpoint between the inferior margin of the last rib and the superior iliac crest in a horizontal plane. Information about smoking status, alcohol consumption, family history of colon cancer, history of colorectal polyps, and history of medication use, including aspirin or nonsteroidal anti-inflammatory drugs (NSAID), was obtained from standardized self-reported questionnaires completed during the health screening program. Although we had information on history of colorectal polyps, we did not have information on performance of colonoscopies prior to the study period among participants without a history of polyps. High risk for colorectal adenoma was defined as either having a history of colorectal polyps or a family history of colorectal cancer. Screening colonoscopies Twenty-six board-certified gastroenterologists performed the colonoscopies after bowel preparation with 4L polyethylene glycol solution (Colyte, Colyte-F, Colonlyte; Dreampharma). The size of each lesion was estimated using open biopsy forceps. The distribution of Participants undergoing routine colonoscopy as part of routine health check-up examinations from January 2006 until June 2009 at Samsung Medical Center, Seoul, Korea (n = 20,500) Excluded for one or more of the following reasons (n = 1,128): - Colonoscopy criteria: - Non-screening colonoscopies, n = Incomplete colonoscopies, n = Participant criteria: -Age <20 or 80 years old, n = 15 - History of colorectal operation or cancer, n = 49 - Inflammatory bowel disease, n = 27 - Foreigner, n = 47 Figure 1. Flowchart of study participants. The study population included consecutive participants undergoing colonoscopy as part of routine health check-up examinations at the Center for Health Promotion of the Samsung Medical Center in Seoul, Korea, from January 2006 to June If a participant had more than one colonoscopy during this study period, we included only the first colonoscopy. Included in analysis (n = 19,372) 500 Cancer Epidemiol Biomarkers Prev; 23(3) March 2014 Cancer Epidemiology, Biomarkers & Prevention

3 Prevalence of Colorectal Adenoma in Koreans colorectal adenomas was classified into proximal colon (cecum, ascending colon, hepatic flexure, and transverse colon) and distal colon (splenic flexure, descending colon, sigmoid colon, and rectum). Advanced adenomas were defined as adenomas with a diameter 10 mm, with a villous component, or with high-grade dysplasia. Statistical analysis The study outcome was the prevalence of colorectal adenomas by decade of age. The precision of the estimates was described using standard errors or 95% confidence intervals (CI). The prevalence of adenomas for the average-risk group was estimated as an approximation to the prevalence in an unscreened population. Adenomas were further classified according to number, size, and histology. The prevalence of adenomas and of advanced adenomas were estimated from robust Poisson and multinomial logistic regression models, respectively, stratified by sex and risk strata (high vs. average risk). In addition, the prevalence of adenomas as a function of age was modeled using restricted cubic splines with knots at the 5th, 27.5th, 50th, 72.5th, and 95th age percentiles (corresponding to 39, 47, 52, 57, and 66 years of age). All participants had information on age, sex, ethnicity, and colonoscopy findings but other covariates had varying proportions of missing data (Table 1). We used multiple imputations with chained equations to address missing data in all analyses (9, 10). Missing covariate patterns were explored and imputation equations refined to create 40 imputed sets, each a result of 200 iterations. The mean and SDs of the imputed data were graphically explored across different iterations and multiple imputed sets as a form of diagnostics. Two sided P-values <0.05 were considered statistically significant. Statistical analyses were performed using Stata version 12.0 (StataCorp). Results The average age of study participants was 52.3 and 51.8 years in men and women, respectively (Table 1). The proportion of participants with a history of colorectal polyps and with a family history of colorectal cancer were 21.1% and 7.3%, respectively, among men, and 10.2% and 8.2%, respectively, among women. The proportion of men and women at high risk for colorectal adenoma was 26.2% and 17.2%, respectively. Among men at average risk of colorectal adenoma, the prevalence of adenomas and of advanced adenomas was 34.5% and 3.1%, respectively (Table 2). The prevalence of men with at least 1, 2, and 3 or more adenomas was 21.6%, 8.1%, and 6.6%, respectively. The prevalence of all types of adenoma increased with age, but the increase was more marked for multiple adenomas, for adenomas 10 mm, and for advanced adenomas. The prevalence of advanced adenomas increased from 0.6% among participants 30 to 39 years of age to 7.4% among those 70 to 79 years of age. Of the 20 cases of colorectal cancer identified, 19 were adenocarcinomas and the other one was a lymphoma. Table 1. Characteristics of participants (N ¼ 19,372) Overall Men Women Characteristic (number of participants with data available) (N ¼ 19,372) (N ¼ 12,625) (N ¼ 6,747) Age, yr (N ¼ 19,372) 52.1 (0.1) 52.3 (0.1) 51.8 (0.1) Current smoker, % (N ¼ 17,655) 20.7 (0.3) 29.6 (0.4) 3.0 (0.2) Current alcohol consumption, % (N ¼ 17,106) 66.1 (0.4) 82.8 (0.4) 32.7 (0.6) Regular exercise, % (N ¼ 17,643) 45.6 (0.4) 44.2 (0.5) 48.2 (0.7) History of colorectal polyps, % (N ¼ 17,272) 17.5 (0.3) 21.1 (0.4) 10.2 (0.4) Family history of colorectal cancer, % (N ¼ 9,196) 7.6 (0.3) 7.3 (0.4) 8.2 (0.5) High risk of adenoma, % (N ¼ 10,587) a 23.2 (0.4) 26.2 (0.5) 17.2 (0.6) Aspirin use, % (N ¼ 16,748) 12.6 (0.3) 15.1 (0.3) 7.6 (0.4) NSAIDs use, % (N ¼ 16,748) 2.8 (0.1) 2.0 (0.1) 4.5 (0.3) BMI, kg/m 2 (N ¼ 18,645) 24.2 (0.1) 24.8 (0.1) 23.0 (0.1) Waist circumference, cm (N ¼ 16,326) 84.0 (0.1) 87.6 (0.1) 77.2 (0.1) Year of colonoscopy 2006 (N ¼ 3,330) 17.5 (0.3) 20.5 (0.4) 11.6 (0.4) 2007 (N ¼ 3,548) 18.7 (0.3) 19.8 (0.4) 16.5 (0.5) 2008 (N ¼ 7,173) 37.9 (0.4) 36.2 (0.5) 41.2 (0.7) 2009 (N ¼ 5,321) 25.9 (0.3) 23.5 (0.4) 30.8 (0.6) NOTE: Values in the table are means (SE) or proportions (SE). Data on age, sex, ethnicity, and colonoscopy findings were available in all participants. Other covariates had variable proportions of missing information as reflected in the first column of the table. The means and proportions presented, however, reflect multiple imputation methods for missing data (see Statistical Methods). a High risk of adenoma defined as having a history of colorectal polyps or a family history of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 23(3) March

4 Yang et al. Table 2. Prevalence of colorectal neoplasms by age group in men (N ¼ 12,625) Age (yr) % (SE%) Overall (N ¼ 12,625) (N ¼ 71) (N ¼ 603) (N ¼ 4,092) (N ¼ 5,405) (N ¼ 2,167) (N ¼ 287) Any adenoma Risk of adenoma Average risk 34.5 (0.5) 10.6 (4.3) 16.9 (1.7) 27.9 (0.8) 36.8 (0.8) 47.0 (1.4) 53.1 (3.7) High risk 41.2 (1.0) 21.1 (12.3) 20.7 (4.2) 33.8 (1.7) 42.4 (1.4) 50.9 (2.1) 49.5 (5.6) Number of adenomas One 21.6 (0.4) 9.9 (3.6) 14.1 (1.4) 19.7 (0.6) 22.6 (0.6) 24.9 (0.9) 23.3 (2.5) Two 8.1 (0.2) 2.8 (2.0) 2.7 (0.7) 5.9 (0.4) 9.0 (0.4) 11.7 (0.7) 8.7 (1.7) Three or more 6.6 (0.2) (0.4) 3.6 (0.3) 6.8 (0.3) 11.7 (0.7) 19.9 (2.4) Largest adenoma size <5 mm 21.8 (0.4) 9.9 (3.6) 11.4 (1.3) 19.1 (0.6) 22.5 (0.6) 27.7 (1.0) 28.6 (2.7) 5 9 mm 11.7 (0.3) 2.8 (2.0) 5.5 (0.9) 8.6 (0.4) 12.8 (0.5) 16.2 (0.8) 17.4 (2.2) 10 mm 2.7 (0.1) (0.3) 1.5 (0.2) 3.1 (0.2) 4.3 (0.4) 5.9 (1.4) Adenoma location Proximal only 15.6 (0.3) 1.4 (1.4) 6.6 (1.0) 12.3 (0.5) 16.3 (0.5) 22.2 (0.9) 21.3 (2.4) Distal only 12.4 (0.3) 9.9 (3.6) 10.0 (1.2) 11.9 (0.5) 12.7 (0.5) 13.3 (0.7) 11.8 (1.9) Proximal and distal 8.3 (0.2) 1.4 (1.4) 1.0 (0.4) 5.1 (0.3) 9.4 (0.4) 12.7 (0.7) 18.8 (2.3) Year (0.9) 8.3 (8.3) 15.7 (4.0) 24.3 (1.4) 34.6 (1.4) 39.9 (2.4) 53.5 (7.7) (1.0) 10.0 (10.0) 12.1 (4.0) 26.0 (1.6) 36.5 (1.5) 47.0 (2.4) 51.8 (6.7) (0.7) 26.7 (11.8) 19.1 (2.6) 30.2 (1.2) 38.0 (1.1) 50.8 (1.8) 45.5 (4.8) (0.9) 8.8 (4.9) 18.3 (2.6) 34.5 (1.5) 44.1 (1.4) 52.1 (2.2) 60.3 (5.6) P temporal trend < <0.001 <0.001 < Advanced adenomas Risk of adenoma Average risk 3.1 (0.2) (0.3) 1.7 (0.2) 3.6 (0.3) 5.1 (0.6) 7.4 (1.9) High risk 2.3 (0.3) (1.1) 1.3 (0.4) 2.4 (0.5) 3.5 (0.8) 2.8 (1.9) Adenoma 10 mm 2.7 (0.1) (0.3) 1.5 (0.2) 3.1 (0.2) 4.2 (0.4) 5.6 (1.4) Villous adenoma 0.3 (0.1) (0.1) 0.4 (0.1) 0.6 (0.2) 0.3 (0.3) High-grade dysplasia 0.1 (0.1) (0.1) 0.1 (0.1) 0.3 (0.1) 0.0 Year (0.4) (1.7) 1.9 (0.5) 4.4 (0.6) 6.2 (1.2) 9.3 (4.5) (0.3) (0.4) 3.4 (0.5) 4.7 (1.0) 10.7 (4.2) (0.2) (0.4) 1.5 (0.3) 2.9 (0.4) 4.3 (0.7) 2.7 (1.6) (0.3) (0.4) 1.7 (0.4) 2.9 (0.5) 3.7 (0.8) 5.1 (2.5) P temporal trend Colorectal cancer Any cancer 0.2 (0.1) (0.1) 0.2 (0.1) 0.1 (0.1) 0.7 (0.5) Adenocarcinoma 0.2 (0.1) (0.1) 0.2 (0.1) 0.1 (0.1) 0.7 (0.5) Lymphoma 0.1 (0.1) (0.1) NOTE: High risk of adenoma defined as having a history of colorectal polyps or a family history of colorectal cancer. Proximal adenomas included adenomas located in the cecum, ascending colon, hepatic flexure, and transverse colon. Distal adenoma included adenomas located in the splenic flexure, descending colon, sigmoid colon, and rectum. Among women at average risk of colorectal adenoma, the prevalence of adenomas and of advanced adenomas were 20.0% and 1.6%, respectively (Table 3). The ageadjusted prevalence ratios (95% CI) for adenomas and advanced adenomas comparing men and women were 1.70 ( ) and 1.72 ( ), respectively. Although the prevalence of adenomas and advance adenomas was higher in men compared with women, the patterns of increasing prevalence of adenomas with age was similar in men and women. We only identified 6 cases of cancer among women, all of them adenocarcinomas. Participants with a family history of colorectal cancer or with a history of colorectal polyps, considered at high 502 Cancer Epidemiol Biomarkers Prev; 23(3) March 2014 Cancer Epidemiology, Biomarkers & Prevention

5 Prevalence of Colorectal Adenoma in Koreans Table 3. Prevalence of colorectal neoplasms by age group in women (N ¼ 6,747) Age (yr) % (SE%) Overall (N ¼ 6,747) (N ¼ 39) (N ¼ 377) (N ¼ 2,274) (N ¼ 2,944) (N ¼ 1,013) (N ¼ 100) Any adenoma Risk of adenoma Average risk 20.0 (0.6) (1.6) 15.3 (0.8) 21.1 (0.9) 30.9 (1.7) 40.1 (5.8) High risk 24.9 (1.5) (2.7) 19.3 (2.3) 25.4 (2.1) 38.3 (3.9) 57.5 (11.6) Number of adenomas One 15.6 (0.4) (1.4) 13.1 (0.7) 16.5 (0.7) 21.4 (1.3) 23.0 (4.2) Two 3.4 (0.2) (0.3) 2.1 (0.3) 3.4 (0.3) 6.7 (0.8) 16.0 (3.7) Three or more 1.8 (0.2) (0.2) 2.0 (0.3) 4.1 (0.6) 5.0 (2.2) Largest adenoma size <5 mm 13.3 (0.4) (1.3) 10.0 (0.6) 13.9 (0.6) 21.0 (1.3) 21.0 (4.1) 5 9 mm 6.2 (0.3) (0.5) 4.9 (0.5) 6.5 (0.5) 9.0 (0.9) 19.0 (3.9) 10 mm 1.4 (0.1) (0.3) 1.0 (0.2) 1.5 (0.2) 2.3 (0.5) 4.0 (2.0) Adenoma location Proximal only 9.9 (0.4) (0.8) 7.0 (0.5) 11.2 (0.6) 14.9 (1.1) 18.0 (3.9) Distal only 8.4 (0.3) (1.2) 7.4 (0.5) 8.0 (0.5) 12.1 (1.0) 16.0 (3.7) Proximal and distal 2.6 (0.2) (0.3) 1.5 (0.3) 2.6 (0.3) 5.2 (0.7) 10.0 (3.0) Year of colonoscopy (1.4) (4.5) 12.0 (2.0) 18.0 (2.1) 38.9 (4.7) 50.0 (15.1) (1.2) (2.3) 18.2 (1.9) 22.1 (1.9) 21.5 (3.4) 36.8 (11.4) (0.8) (2.4) 15.7 (1.2) 21.9 (1.2) 29.0 (2.2) 43.6 (8.0) (0.9) (2.3) 16.3 (1.4) 23.0 (1.4) 38.9 (2.7) 46.7 (9.3) P temporal trend Advanced adenomas Risk of adenoma Average risk 1.6 (0.2) (0.3) 0.8 (0.2) 1.9 (0.3) 2.7 (0.6) 2.5 (1.8) High risk 1.7 (0.4) (0.8) 0.9 (0.5) 2.9 (1.4) 9.3 (6.4) Adenoma 10 mm 1.4 (0.1) (0.3) 1.0 (0.2) 1.5 (0.2) 2.2 (0.5) 4.0 (2.0) Villous adenoma 0.3 (0.1) (0.1) 0.3 (0.1) 0.4 (0.2) 1.0 (1.0) High-grade dysplasia 0.1 (0.1) (0.1) 0.1 (0.1) 0.5 (0.2) 0.0 Year of colonoscopy (0.5) (0.7) 0.6 (0.4) 7.4 (2.5) (0.3) (0.4) 1.9 (0.6) (5.3) (0.2) (0.3) 1.9 (0.4) 2.6 (0.8) 5.1 (3.6) (0.3) (0.6) 1.4 (0.4) 2.0 (0.5) 2.7 (0.9) 3.3 (3.3) P temporal trend Colorectal cancer Any cancer 0.1 (0.1) (0.1) 0.1 (0.1) 1.0 (1.0) Adenocarcinoma 0.1 (0.1) (0.1) 0.1 (0.1) 1.0 (1.0) Lymphoma NOTE: High risk of adenoma defined as having a history of colorectal polyps or a family history of colorectal cancer. Proximal adenomas included adenomas located in the cecum, ascending colon, hepatic flexure, and transverse colon. Distal adenoma included adenomas located in the splenic flexure, descending colon, sigmoid colon, and rectum. risk for colorectal adenomas, had a significantly higher prevalence of adenomas compared with participants of average risk (36.9% vs. 29.1%; age- and sex-adjusted prevalence ratio ¼ 1.16; 95% CI, ; Table 4). The higher prevalence of adenomas in high-risk compared with average-risk participants was evident across all ages (Fig. 2A). For advanced adenomas, however, participants at high risk had a lower prevalence compared with those at average risk (2.1% vs. 2.5%; age- and sex-adjusted prevalence ratio ¼ 0.74; 95% CI, ), particularly among men. In more detailed analyses by age, high-risk participants had lower prevalence of advanced adenomas Cancer Epidemiol Biomarkers Prev; 23(3) March

6 Yang et al. Table 4. Prevalence of colorectal adenoma and advanced adenoma by gender and year of colonoscopy (N ¼ 19,372) Overall (N ¼ 19,372) Men and women Men Women <50 yr (N ¼ 7,456) 50 yr (N ¼ 11,916) P value <50 yr (N ¼ 4,766) 50 yr (N ¼ 7,859) P value <50 yr (N ¼ 2,690) 50 years, (N ¼ 4,057) P value Any adenoma Risk of adenoma 0.86 a 0.39 a 0.58 a Average risk 29.1 (0.4) 21.6 (0.6) 34.1 (0.5) < (0.7) 40.1 (0.7) < (0.8) 23.9 (0.8) <0.001 High risk 36.9 (0.8) 27.7 (1.3) 41.4 (1.0) < (1.6) 45.3 (1.2) < (2.0) 29.7 (1.9) <0.001 P value <0.001 <0.001 < < Colonoscopy year 0.96 b 0.98 b 0.46 b (0.8) 20.6 (1.1) 33.6 (1.0) 23.4 (1.3) 36.5 (1.2) 11.5 (1.8) 23.7 (2.0) (0.8) 21.9 (1.1) 34.9 (1.0) 24.8 (1.5) 40.0 (1.2) 16.3 (1.7) 22.4 (1.7) (0.5) 23.2 (0.8) 35.3 (0.7) 28.7 (1.1) 41.8 (0.9) 14.6 (1.1) 24.3 (1.0) (0.6) 24.4 (0.9) 39.1 (0.9) 31.0 (1.3) 47.0 (1.2) 14.8 (1.2) 27.7 (1.2) P value trend < <0.001 <0.001 < Advanced adenoma Risk of adenoma 0.11 a 0.47 a 0.05 a Average risk 2.5 (0.1) 1.2 (0.1) 3.4 (0.2) < (0.2) 4.2 (0.3) < (0.2) 2.2 (0.3) <0.001 High risk 2.1 (0.3) 1.5 (0.3) 2.5 (0.3) (0.4) 2.7 (0.4) (0.7) 1.7 (0.6) P value Colonoscopy year 0.10 b 0.51 b 0.66 b (0.3) 1.7 (0.4) 4.4 (0.5) 1.9 (0.4) 5.0 (0.6) 1.0 (0.6) 2.2 (0.7) (0.3) 1.1 (0.3) 3.3 (0.4) 1.3 (0.4) 4.0 (0.5) 0.7 (0.4) 1.6 (0.5) (0.2) 1.1 (0.2) 2.9 (0.2) 1.3 (0.3) 3.3 (0.3) 0.8 (0.3) 2.2 (0.4) (0.2) 1.4 (0.2) 2.8 (0.3) 1.5 (0.3) 3.2 (0.4) 1.2 (0.4) 2.2 (0.4) P value trend NOTE: Prevalence estimates are presented as % (SE%). a P value for interaction between age (categorized as <50 and 50 years) and risk stratum. b P value for interaction between age (categorized as <50 and 50 years) and trend over years of colonoscopy. after the 5th decade of life (Fig. 2B). Finally, the prevalence of colorectal adenomas significantly increased every year of the study, whereas the prevalence of advanced adenomas decreased in men (Table 4). Discussion In this large cross-sectional study of asymptomatic men and women attending a health screening program, among those at average risk of colorectal adenoma we found that 34.5% of men and 20.0% of women had prevalent colorectal adenomas, and 3.1% of men and 1.6% of women had prevalent advanced adenomas. The prevalence of colorectal adenomas and of advanced adenomas increased significantly with age in both men and women, particularly for multiple, larger, and advanced adenomas. The prevalence of adenomas increased annually over the study period in both men and women. Our estimates of the prevalence of colorectal adenomas are consistent with previous studies based on more selected and smaller screening samples (7, 11). In one study, the prevalence of colorectal adenomas among average risk asymptomatic Koreans 50 years of age or older were 39.9% and 23.0% among men and women, respectively (7), whereas in another study, the prevalence among Korean men 40 to 69 years of age was 36.3% (11). These estimates are actually higher than estimates from studies in Western countries. In the United States, a large study from the Clinical Outcomes Research Initiative database reported that adenoma detection rates in men 50 to 59, 60 to 69, and 70 to 79 years of age were 27.8%, 33.6%, and 34.3%, respectively (12), and a retrospective analysis of Northern California Kaiser Permanente participants reported adenoma prevalence of 30.6% and 20.2%, respectively, for men and women 50 years of age or older (13). The prevalence estimates observed in our study and in an earlier survey conducted in 2003 to 2004 among 11 university hospitals in Korea (40.7%; ref. 7) suggest that the prevalence of adenomas in participants 50 years of age and older in Korea is high and possibly higher than in Western countries. The prevalence of colorectal adenomas in participants 40 to 49 years of age at average risk in our study was 27.9% and 15.3% in men and women, respectively. Current guidelines in Korea, based on guidelines published by the American College of Gastroenterology and the U.S. Multi-Society Task Force on Colorectal Cancer (8, 14 16), recommend screening colonoscopy after age 50 in both men and women at average risk. There is an ongoing debate on the appropriateness of these criteria to different ethnicities and different countries, as the application of 504 Cancer Epidemiol Biomarkers Prev; 23(3) March 2014 Cancer Epidemiology, Biomarkers & Prevention

7 Prevalence of Colorectal Adenoma in Koreans Figure 2. Prevalence of adenoma and advanced adenoma by age, sex, and risk strata. Adjusted prevalence estimates of adenoma (A) and advanced adenoma (B) were derived from spline regression models using restricted cubic splines with knots at the 5th, 27.5th, 50th, 72.5th, and 95th age percentiles (corresponding to 39, 47, 52, 57, and 66 years) of the distribution of age. The models adjusted for age, sex, risk strata, and included age sex and age risk strata interactions. these guidelines to different populations has often not been thoroughly assessed. The prevalence of colorectal adenomas in men and women 40 to 49 years of age in our study population was much higher compared with other Western estimates (15, 17 19). Indeed, the prevalence in our study was comparable with U.S. participants 40 to 49 years of age with a first-degree relative with adenomas (26.7%), although the gender ratio differs slightly (20). Given the high prevalence of adenomas detected in our study in men and women 40 to 49 years of age, costeffectiveness studies should be conducted to evaluate a screening approach tailored to the Korean population. In our study, the prevalence of colorectal adenoma significantly increased annually from 2006 to 2009 in men and women older than 50. Although temporal changes in risk factors, such as diet, physical activity, obesity, and smoking, may have influenced this increasing prevalence, a more likely explanation may be higher detection rates because of improved equipment or colonoscopy techniques over time. Similar to other Korean studies and in contrast with Western estimates, the high prevalence of adenomas was accompanied by a lower prevalence of advanced adenomas. The prevalence of advanced adenomas among participants in our study was 3.6%, 5.1%, and 7.4% for men 50 to 59, 60 to 69, and 70 to 79 years of age, respectively, and 1.9%, 2.7%, and 2.5% for women 50 to 59, 60 to 69, and 70 to 79 years of age, respectively. These estimates are similar to estimates from previous Korean studies of 2.5% to 4.1% in participants 50 years of age and older (6, 7), but are lower than estimates from Western studies of 4.4% to 10.5% (21 23). The reasons for the lower prevalence of advance adenomas among Koreans are unclear. Our study also identified a lower prevalence of advanced adenomas in participants considered at high risk, as well as a decreasing prevalence of advanced adenomas from 2006 to 2009 in men 50 years of age and older. Earlier detection and previous removal of adenomas in screening programs may have reduced the occurrence of advanced adenomas in participants considered at high risk of colorectal adenoma, particularly in a cohort assembled from health screening visits. The time lag between the previous and current colonoscopy among these participants may be too short for the further development of advanced adenomas. In addition, the relatively lower prevalence of advanced adenomas in participants 50 years of age or older may reflect cohort effects, as elder participants may belong to cohorts with lower risks of progression of adenomas. There are several limitations in our study. First, our study was performed in a large Korean health screening center and generalizability of our results to other populations is unknown. The screening population had a higher socioeconomic status and might be more health conscious compared with the general population. Screening colonoscopies are not reimbursed by the Korean National Health Insurance Corporation. In our sample, approximately 30% of screening colonoscopies were paid for by the employers and 70% paid by the participants (out of pocket). Our results may thus not generalize to populations with different coverage structure for screening colonoscopies. Second, misclassification might have occurred during histology reporting and during polyp size measurement. However, colonoscopists were not aware of the study objectives and these measurement errors were more likely to be nondifferential in nature. Third, the questionnaire used in our center included history of colorectal polyp but not of colorectal adenoma. As a consequence, participants with a history of nonneoplastic polyps may have been included in the high-risk group thus underestimating the prevalence of adenomas among high-risk participants. Fourth, Cancer Epidemiol Biomarkers Prev; 23(3) March

8 Yang et al. although we excluded repeated colonoscopies during the study period, we did not have information on the performance of colonoscopies before the study period, except in participants who reported a history of polyps. As a consequence, the prevalence of polyps for average-risk participants in our study is likely to underestimate the prevalence in unscreened individuals, as the average-risk group in our study included participants with prior colonoscopy but no history of polyps. The strengths of our study include the large number of participants who underwent a health screening colonoscopy. We were able to evaluate the age-specific prevalence of colorectal adenoma, specifically among the younger and older populations, because of the wide age range of participants. The use of data from multiple years also allowed us to perform temporal analysis from 2006 to In conclusion, the prevalence of colorectal adenomas in our study population was comparable and possibly higher than the prevalence reported in Western countries, and this prevalence increased every year for the duration of the study. The prevalence of colorectal adenoma started rising at earlier ages in men compared with women, but the prevalence of adenomas among men and women 40 to 49 years of age was above the proposed minimum detection rates for screening colonoscopy. Cost-effectiveness studies should investigate the optimal age for starting colonoscopy screening among Korean men and women. Furthermore, additional studies should be conducted to identify the causes for the increasing prevalence of colorectal adenomas in Korean men and women over time. Disclosure of Potential Conflicts of Interest No potential conflicts of interest were disclosed. Authors' Contributions Conception and design: M.H. Yang, J.C. Rhee, E. Guallar, J. Cho Development of methodology: S. Rampal, E. Guallar, J. Cho Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): M.H. Yang, J. Sung, Y.-H. Choi, H.J. Son, J.H. Lee, D.K. Chang, J. Cho Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): S. Rampal, J. Sung, J.H. Lee, D.K. Chang, E. Guallar, J. Cho Writing, review, and/or revision of the manuscript: M.H. Yang, S. Rampal, J. Sung, Y.-H. Choi, J.H. Lee, Y.-H. Kim, D.K. Chang, J.C. Rhee, E. Guallar, J. Cho Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): S. Rampal, J. Cho Study supervision: P.-L. Rhee, E. Guallar, J. Cho The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. 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10 The Prevalence of Colorectal Adenomas in Asymptomatic Korean Men and Women Moon Hee Yang, Sanjay Rampal, Jidong Sung, et al. Cancer Epidemiol Biomarkers Prev 2014;23: Published OnlineFirst January 17, Updated version Access the most recent version of this article at: doi: / epi Cited articles This article cites 23 articles, 2 of which you can access for free at: alerts Sign up to receive free -alerts related to this article or journal. Reprints and Subscriptions Permissions To order reprints of this article or to subscribe to the journal, contact the AACR Publications Department at pubs@aacr.org. To request permission to re-use all or part of this article, use this link Click on "Request Permissions" which will take you to the Copyright Clearance Center's (CCC) Rightslink site.