Journal of Cancer 2016, Vol.

7 681

Ivyspring
International Publisher
Journal of Cancer
2016; 7(6): 681-686. doi: 10.7150/jca.14264
Research Paper

Effect of Ulcerative Colitis on Incidence of Colorectal

Cancer: Results from the Nationwide Population-Based
Cohort Study (2003-2013)
Jung-kyu Choi1, Dong-Wook Kim1, Sang-Yun Shin2, Eun-Cheol Park3, Jung-Gu Kang4
1. Institute of Health Insurance & Clinical Research, National Health Insurance Service Ilsan Hospital, Goyang, Korea
2. Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Korea
3. Department of Preventive Medicine & Institute of Health Services Research, Yonsei University College of Medicine, Seoul, Korea
4. Department of Surgery, National Health Insurance Service Ilsan Hospital, Goyang, Korea

Corresponding authors: Eun-Cheol Park, MD, PhD, Department of Preventive Medicine & Institute of Health Services Research, Yonsei University of College
of Medicine, Seoul, Korea. 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea. Tel: +82-2-2228-1862, Fax: +82-2-392-8133, e-mail: [email protected].
Jung-Gu Kang, MD, PhD, Department of Surgery, National Health Insurance Service Ilsan Hospital, Goyang, Korea. 100 Ilsan-ro, Ilsandong-gu, Goyang-si,
Gyeonggi-do, 410-719, Republic of Korea. Tel: +82-31-900-0010, Fax: +82-31-900-0343, e-mail: [email protected]

Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See
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Received: 2015.10.29; Accepted: 2016.01.22; Published: 2016.03.21

Abstract
Purpose: The colorectal cancer (CRC) is the third leading cause of death in Korea. Ulcerative
colitis (UC) is regarded as a risk factor of CRC. The aim of study is to confirm the incidence of
CRC among subjects with and without a diagnosis of UC based on a sample of the Korean
population. This study identified the effect of UC on incidence of CRC in Korea.
Method: The data were from the population-based cohort containing National Health Insurance
(NHI) claims from 2002 to 2013. We washed out first year (2002) for newly detected cases.
Subjects who were under 20 years of age, diagnosed UC and CRC in 2002 development of CRC
before diagnosis of UC since 2003, were excluded from analyses. Among 745,641 subjects during
11 years of follow-up (2003-2013), 7,448 patients with CRC were newly detected. Cox
proportional hazard regression model was used to estimate the hazard ratio (HR) of UC for CRC
incidence. Confounding variables including gender, baseline age, type of social security, income
level, residence, Charlson Comorbidity Index, hypertension and diabetes mellitus were
incorporated into the model.
Results: Overall annual incidence of UC and CRC were 6.7 and 95.4 per 100,000 during 11 years
(2003~2013), respectively. Among 522 of newly detected UC cases, CRC incident cases were 12
cases during 11 years. The effects were stronger for male. Advancing age and Charlson
Comorbidity Index, hypertension and diabetes mellitus increased the risk of CRC. This study
showed that the adjusted hazard ratio of UC in incidence of CRC is 1.92 (95% confidence interval:
1.09-3.38). Also, male patients with UC have more HR than female patients with UC.
Conclusion: The results of this study showed that patients with UC are the high risk group in
incidence of CRC. Furthermore, the effects of UC in male patients are higher than those in female.
The future study is needed to identify the effect of UC on mortality of CRC.
Key words: Colorectal cancer, ulcerative colitis, Korea, population-based cohort study

Introduction
The crude incidence rate per 100,000 of colorectal annual percentage change was 5.3% (male: 5.7%,
cancer (CRC) of 2012 is 57.6 (male: 69.3; female 45.9) female: 4.3%) during 14 years (1999 2012).[1] The
that is the third highest occurring cancer in Korea, and crude death rate per 100,000 of CRC of 2012 was 16.2

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Journal of Cancer 2016, Vol. 7 682

(male: 18.5; female: 13.8) that is the fourth common approved by the Institutional Review Board (IRB) of
cause of cancer death. National Health Insurance Medical Center (NHIMC)
The incidence of colorectal cancer has increased (IRB File No.: NHIMC 2015-07-029). This study used
by 2 to 4 times during the past few decades in many National Sample Cohort data (NHIS-2016-2-026),
Asian countries, including South Korea, China and provided by NHIS.
Japan.[2] One of the reasons for increasing CRC is
changes in dietary habits and lifestyle.[3, 4] Increased
consumption of meat and animal fat might be a
reason for rising incidence of colorectal cancer.
The incidence rate of CRC was high in patients
with long-term ulcerative colitis (UC).[5-7] The
prevalence for UC was higher in Western countries
than in Asian countries.[8-11] Even though the
prevalence in Western countries has begun to
stabilize, the prevalence of UC in Asia is steadily
increasing even now.[9-11] Recent studies on UC
effects on incidence of CRC are conducted in Eastern
countries. Registration program for Rare Intractable
Disease (RID), including UC, was established in 2006.
According to registration program, annual incidence
for UC was 4.6 per 100,000.[12]
While the incidence of UC in Korea is still lower
than those in Western countries, it is rapidly
increasing.[13] It is anticipated that the incidence of
UC-associated CRC will also increase. It is important
to identify risk factors that influence developing CRC.
The purpose of this study was to identify the Figure 1. Flowchart of the subjects included for analysis
association between UC and CRC using nationwide
population-based cohort data in Korea.
Study Variables
Method The diagnosis of CRC was a dependent variable.
Data and Study Population The CRC consists of malignant neoplasm of colon
(C18), malignant neoplasm of rectosigmoid junction
National Health Insurance Service (NHIS) has
(C19) and malignant neoplasm of rectum (C20). CRC
established the nationwide cohort containing medical
is a disease originating from the epithelial cells lining
care claims from 2002, the baseline year. The number
the colon or rectum of the gastrointestinal tract.
of cohort population was 1,025,340 accounting for
The diagnosis of UC was an independent
about 2% of total Korean population. The cohort was
variable. According to the 10th version of
followed until 2013. The sampling method is a
International Classification of Diseases (ICD-10), UC
stratified sampling by gender, age, and income level.
was designated with the code of main sick K51. The
Gender and age were categorized into 2 (male,
annual incidence of UC was 4.6 per 100,000 during 7
female) and 18 (0, 1~79 (5yrs), 80+). Income level was
years (2006-2012).[12] On average, patients with UC
categorized into 41 (medical aid: 1, industrial worker
have used clinics or hospitals 6.4 times per year in
(IW): 20, self-employee (SE): 20). Total stratified
Korea. Based on annual incidence and utilization, the
categories were 1,476 strata.
patients with UC were defined as visiting clinics or
We washed out first year (2002) for newly
hospitals 4 times annually.
detected cases. Subjects who were under 20 years of
Confounding variables included gender,
age (n=278,524), diagnosed UC (n=103) and CRC
baseline age, type of social security, income level,
(n=1,029) in 2002, and development of CRC before
residence, Charlson Comorbidity Index (CCI),[14, 15]
diagnosis of UC since 2003 (n=64) were excluded from
hypertension and diabetes mellitus. Age was divided
analyses (figure 1).
to 4 groups (20-34, 35-49, 50-64, 65 and over years).
Thus, the final sample included 745,641 subjects:
The type of social security consists of medical aid and
366,251 male (49.1%), 379,390 female (50.9%). The data
health insurance in Korea. Health insurance was
was observed for 7,807,280 person-years in subject.
divided into industrial worker (IW) and self-employer
All components and procedures of this study were
(SE). Income level was recoded into 5 categories, from

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 Journal of Cancer 2016, Vol. 7 683

quintile 1 (low) to quintile 5 (high), according to Statistical Analysis

insurance premiums of householders. The residence We compared independent variables using
was divided into capital city (Seoul), big cities, x2-test according to the presence of CRC. The results
medium and small cities and rural areas. The CCI was were expressed as frequency (%). After performing
recoded into 3 categories (0, 1, 2). The hypertension preliminary analyses, we used Cox proportional
and diabetes mellitus were defined as cases of subjects hazard regression model to estimate the hazard ratio
diagnosed with I10 ~ I15 and E10 ~ E14 in 2003. (HR) for the incidence of CRC. Covariates included
Survival time was the number of months between the baseline age (ref: 20-34 years old), type of social
baseline and the event of CRC. security (ref: Health insurance (IW)), income level (ref:
Table 1. General characteristics of subjects, according to 1 quintile), residence (ref: rural areas), CCI (ref: 0),
presence of colorectal cancer. Unit: N, (%). hypertension (ref: non-diagnosed), diabetes mellitus
(ref: non-diagnosed). Kaplan-Meier survival curve
With
Total No
With
p-value method was conducted to determine probability of
Cancer
Cancer incidence for group with UC relative to the reference
738,193 7,448
Total 745,641
(99.0) (1.0) group (non-diagnosed). Statistical analysis was
Male 366,251
362,047 4,204
<.0001
performed using the SAS version 9.2. P-value < 0.05
(98.8) (1.2)
Gender was considered to be significant.
376,146 3,244
Female 379,390
(99.1) (0.9)
20 ~ 34 269,032
268,630 402
<.0001
Results
(99.8) (0.2)
255,684 1,850 Baseline characteristics of subjects were shown
35 ~ 49 257,534
Age
(99.3) (0.7) according to incidence of CRC (Table 1). There were
136,752 3,076
50 ~ 64 139,828
(97.8) (2.2)
7,448 new cases of CRC during 11 years (2003~2013),
77,127 2,120 4,204 of which occurred in male and 3,244 of which
65 79,247
(97.3) (2.7) occurred in female. The incidence of CRC was higher
21,854 184
Medical aid 22,038
(99.2) (0.8)
0.0040 in male than in female. CRC developed in 2.3% of the
Type of
social
Health
362,785
359,050 3,735 UC group and 1.0% in the non-UC group. Figure 2
insurance (IW) (99.0) (1.0)
security shows the difference in development of CRC
Health 357,289 3,529
insurance (SE)
360,818
(99.0) (1.0) according to diagnosis of UC. Risk of CRC was over 2
1 quintile(low) 123,699
122,563 1,136
<.0001 fold higher in subjects with UC. The incidence of UC
(99.1) (0.9)
120,325 1,027
was 6.7 per 100,000 from 2003 to 2013. The incidence
2 quintile 121,352
(99.2) (0.8) of CRC was 95.4 per 100,000 from 2003 to 2013. 12 of
143,287 1,228 the patients with UC (n=522) were diagnosed CRC.
Income level 3 quintile 144,515
(99.2) (0.8)
165,322 1,610 Overall, annual incidence of CRC in male and female
4 quintile 166,932
(99.0) (1.0) were 110.2 and 81.2 per 100,000. Average durations at
186,696 2,447
5 quintile(high) 189,143
(98.7) (1.3)
CRC diagnosis of patients with UC were 3.39 year.
162,051 1,845
Seoul 163,896 <.0001
(98.9) (1.1)
193,071 1,759
Big cities 194,830
(99.1) (0.9)
Residence
Medium, small 303,063 2,824
305,887
Cities (99.1) (0.9)
80,008 1,020
Rural area 81,028
(98.7) (1.3)
544,897 4,414
0 549,311 <.0001
(99.2) (0.8)
Charlson
124,718 1,635
Comorbidity 1 126,353
(98.7) (1.3)
Index
68,578 1,399
2 69,977
(98.0) (2.0)
676,993 5,930
Non-Diagnosed 682,923 <.0001
(99.1) (0.9)
Hypertension
61,200 1,518 Figure 2. Difference in development of CRC according to diagnosis of UC
Diagnosed 62,718
(97.6) (2.4)
709,304 6,723
Non-Diagnosed 716,027 <.0001
Diabetes (99.1) (0.9)
mellitus 28,889 725 Table 2 showed the risk factors of being
Diagnosed 29,614
(97.5) (2.5) diagnosed with CRC during the follow-up period. HR
737,683 7,436
Ulcerative
Non-Diagnosed 745,119
(99.0) (1.0)
0.0028 of UC in CRC incidence of female (0.63 (95%
colitis
Diagnosed 522
510
12 (2.3)
confidence interval (CI): 0.60-0.65)) was lower than
(97.7)
male. HRs of age group steadily increased in CRC
IW: industrial worker, SE: self-employee

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 Journal of Cancer 2016, Vol. 7 684

incidence (4.73 (95% CI: 4.24-5.27) in 30-49 years old, Table 2. Risk factor influencing the incidence of colorectal cancer
14.40 (95%.CI: 12.96-16.00) in 50-64 years old, 22.39 HR 95% CI
(95% CI: 20.04-25.02) in 65 years old and over) than Gender (ref: Male) 1.00
Female 0.63 (0.60-0.65)
reference group (20-34 years old). HR medical aid Age (ref: 20 ~ 34) 1.00
group was 0.66 (95% CI: 0.56-0.78) than health 35 ~ 49 4.73 (4.24-5.27)
50 ~ 64 14.40 (12.96-16.00)
insurance IW group. HR of highest income level was
65 22.39 (20.04-25.02)
1.18 (95% CI: 1.10-1.28) than the lowest income group. Type of social security (ref: Health 1.00
HR of group residing in Seoul was 1.18 (95% CI: insurance_IW)
Medical aid 0.66 (0.56-0.78)
1.09-1.28) than group residing in rural area. HRs of Health insurance(SE) 0.96 (0.91-1.00)
group with CCI=1 and 2 were 1.12 (95% CI: Income level (ref: 1 quintile) 1.00
2 quintile 1.04 (0.95-1.13)
1.05-1.18) and 1.29 (95% CI: 1.20-1.37) than group with 3 quintile 1.03 (0.95-1.13)
CCI=0, respectively. HRs of group with hypertension 4 quintile 1.06 (0.98-1.15)
and diabetes mellitus were 1.13 (95% CI: 1.06-1.20) 5 quintile (high) 1.18 (1.10-1.28)
Residence (ref: Rural area) 1.00
and 1.15 (95% CI: 1.06-1.25) than group of healthy Seoul 1.18 (1.09-1.28)
subjects, respectively. HR of patients with UC was Big cities 0.96 (0.88-1.03)
Medium, small Cities 0.95 (0.89-1.03)
1.92 (95% CI: 1.09-3.38) than group without UC in Charlson Comorbidity Index (ref: 0) 1.00
incidence of CRC. 1 1.12 (1.05-1.18)
Figure 3 showed the results of Kaplan-Meier 2 1.29 (1.20-1.37)
Hypertension (ref: Non-diagnosed) 1.00
survival curves. The incidence probability of patients Diagnosed 1.13 (1.06-1.20)
with UC was higher than the group without UC. The Diabetes mellitus (ref: Non-diagnosed) 1.00
Diagnosed 1.15 (1.06-1.25)
incidence probability of male with UC was higher UC (ref: Non-diagnosed) 1.00
than that of female with UC. Diagnosed 1.92 (1.09-3.38)
IW: industrial worker, SE: self-employee

Discussion
This study was conducted to identify the UC
effect on the CRC incidence. This study confirms
previous findings that UC patients have a higher
frequency of CRC than non-UC patients.
Furthermore, male UC patients are at higher risk than
female UC patients.
According to results, the annual incidence of UC
and CRC were 6.7 and 95.4 per 100,000 during 11
years (2003~2013). In previous study using
registration program for RID in Korea, the annual
incidence of UC was 4.6 per 100,000 during 7 years
(2006~2012).[12] The crude incidence rate per 100,000
of CRC of 2012 was 57.6 (male: 69.3; female 45.9) in
2012.[1] The reason why incidence of UC and CRC in
this study might have excluded subjects under 20
years of age from analysis, is that subjects who were
less than 20 years of age account for about 25% of the
entire population.
CRC most frequently results from mutations in
the Wnt signaling pathways that increases signaling
activity. The mutations occur in the intestinal crypt
stem cell.[16] The risk factors of CRC include male
gender, increasing age, high intake of fat, alcohol or
red meat, obesity, income, smoking, a lack of physical
exercise, and family history of CRC.[17-19] The UC is
associated with development of CRC.[5-7, 19, 20] The
difference in result of analyses was explained by
Figure 3. Kaplan-Meier curve of subjects by gender over 10 years, according to
presence of ulcerative colitis
different methodology, target populations and
follow-up period.

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Journal of Cancer 2016, Vol. 7 685

A meta-analysis on the incidence of accumulated data via electronic data interchange

UC-associated CRC found that cumulative incidence (EDI) in Korea.
of CRC was 2% at 10-year, 8% at 20-year and 18% at This study had the following limitations. First,
30-year follow-up.[21] In case of Korea, the data based on claims data included only information
cumulative incidence of UC-associated CRC was 0.7% on each episode of health care utilization and
at 10-year, 7.9% at 20-year, and 33.2% at 30-year expenditure. Claim data used in analysis did not
follow-up.[22] According to the results, the include clinical findings and disease severity. The
cumulative incidence of UC-associated CRC was 2.3% variables used in this study were limited. Also,
at 11-year follow-up. important co-variates associated with risk of CRC in
Some epidemiologic studies have shown a UC are not available for the cohort thus limiting the
higher risk of CRC in male than in female. This value of the findings. The factors that influenced
difference in risk of CRC between genders is not association between UC and CRC were age at initial
easily explained.[19] Increasing age is associated with diagnosis, life style, and family history of CRC.[32-34]
an increased risk of CRC.[18] Socio-demographic Second, follow-up period was short (11 years), which
indicators, such as income and residence might might have precluded the detection of significant
partially explain the increased incidence of CRC.[17, effects of UC on subsequent incidence of CRC. The
23] Furthermore, the HR of CRC of the highest income incidence of CRC begins to increase 8 or 10 years after
level is significantly higher than that of lowest income the initial diagnosis of UC.[19, 30, 35]
level. Regional differences in screening also might In conclusion, the cancer caused financial and
affect detection of CRC. Risk factors associated with psychological burden to the caregiver, as well as pain
incidence of CRC are diagnoses of hypertension and of patients. CRC is a disease attributable to
diabetes mellitus.[18, 24] Finding from this study inappropriate behavior patterns and lifestyle.
revealed that patients with hypertension or diabetes Prevention is the best cure for cancer. To reduce the
mellitus might be more likely to be diagnosed as CRC incidence of CRC in patients with UC, it is important
than healthy people without hypertension or diabetes to identify predictive and protective factors for CRC.
mellitus. Developing cancer prevention strategies might be
In Korea, the target cancers of NCSP (National helpful in containing the incidence of cancer to
Cancer Screening Program) include stomach cancer, selected high-risk groups.
breast cancer, CRC, liver cancer, and cervical cancer. It
is recommended for individuals aged 50 years to get Abbreviations
CRC screening on a yearly basis. CRC screenings are CRC: Colorectal Cancer; UC: Ulcerative Colitis;
performed for screening items stipulated by the RID: Rare Intractable Disease; NHIS: National Health
health screening implementation standards such as Insurance Service; IW: Industrial Worker; SE:
Fecal Occult Blood Test (FOBT), double-contrast Self-Employee; NHIMC: National Health Insurance
examination of the colon, colonoscopy exam, and Medical Center; ICD: International Classification of
biopsy. Total inspection rate of cancer screening and Diseases; CCI: Charlson Comorbidity Index; HR:
inspection rate of CRC screening were 43.5% and Hazard Ratio; NCSP: National Cancer Screening
30.7% in 2013.[25] The inspection rate of CRC Program; FOBT: Fecal Occult Blood Test; EDI:
screening was lowest among the cancer screenings. Electronic Data Interchange.
There are a number of diseases related to UC.
Some studies found a highly increased risk for Acknowledgements
lymphoma and leukemia in patients with UC.[26, 27] The study was supported by the grant of the
The patients with UC have an increased risk of Institute of Health Insurance & Clinical Research of
developing connective tissue and brain cancer in NHIMC.
Sweden.[28] There was an increased risk of
hepatobiliary cancer and non-melanoma skin cancer Competing Interests
among patients with UC.[19, 29, 30] In addition, an The authors have declared that no competing
Italian population-based study showed an increased interest exists.
risk for Hodgkins disease among patients with
UC.[31] References
The source used in analysis was 1. Jung KW, Won YJ, Kong HJ, Oh CM, Cho H, Lee DH, et al. Cancer statistics in
population-based representative data containing all Korea: incidence, mortality, survival, and prevalence in 2012. Cancer research
and treatment : official journal of Korean Cancer Association. 2015; 47: 127-41.
medical claims and checkup results of population 2. Sung JJ, Lau JY, Goh KL, Leung WK, Asia Pacific Working Group on
Colorectal C. Increasing incidence of colorectal cancer in Asia: implications for
from 2002 to 2013. A number of studies have been screening. The Lancet Oncology. 2005; 6: 871-6.
carried out to identify the cause of disease utilizing

http://www.jcancer.org
 Journal of Cancer 2016, Vol. 7 686
3. Chiu BC, Ji BT, Dai Q, Gridley G, McLaughlin JK, Gao YT, et al. Dietary factors 33. Askling J, Dickman PW, Karlen P, Brostrom O, Lapidus A, Lofberg R, et al.
and risk of colon cancer in Shanghai, China. Cancer epidemiology, biomarkers Family history as a risk factor for colorectal cancer in inflammatory bowel
& prevention : a publication of the American Association for Cancer Research, disease. Gastroenterology. 2001; 120: 1356-62.
cosponsored by the American Society of Preventive Oncology. 2003; 12: 201-8. 34. Brackmann S, Andersen SN, Aamodt G, Langmark F, Clausen OP, Aadland E,
4. Yiu HY, Whittemore AS, Shibata A. Increasing colorectal cancer incidence et al. Relationship between clinical parameters and the colitis-colorectal cancer
rates in Japan. International journal of cancer Journal international du cancer. interval in a cohort of patients with colorectal cancer in inflammatory bowel
2004; 109: 777-81. disease. Scandinavian journal of gastroenterology. 2009; 44: 46-55.
5. Greenstein AJ, Sachar DB, Smith H, Janowitz HD, Aufses AH, Jr. A 35. Langholz E, Munkholm P, Davidsen M, Binder V. Colorectal cancer risk and
comparison of cancer risk in Crohn's disease and ulcerative colitis. Cancer. mortality in patients with ulcerative colitis. Gastroenterology. 1992; 103:
1981; 48: 2742-5. 1444-51.
6. Isbell G, Levin B. Ulcerative colitis and colon cancer. Gastroenterology clinics
of North America. 1988; 17: 773-91.
7. Chambers WM, Warren BF, Jewell DP, Mortensen NJ. Cancer surveillance in
ulcerative colitis. The British journal of surgery. 2005; 92: 928-36.
8. Yang SK, Loftus EV, Jr., Sandborn WJ. Epidemiology of inflammatory bowel
disease in Asia. Inflammatory bowel diseases. 2001; 7: 260-70.
9. Baumgart DC, Carding SR. Inflammatory bowel disease: cause and
immunobiology. Lancet. 2007; 369: 1627-40.
10. Thia KT, Loftus EV, Jr., Sandborn WJ, Yang SK. An update on the
epidemiology of inflammatory bowel disease in Asia. The American journal of
gastroenterology. 2008; 103: 3167-82.
11. Asakura K, Nishiwaki Y, Inoue N, Hibi T, Watanabe M, Takebayashi T.
Prevalence of ulcerative colitis and Crohn's disease in Japan. Journal of
gastroenterology. 2009; 44: 659-65.
12. Kim HJ, Hann HJ, Hong SN, Kim KH, Ahn IM, Song JY, et al. Incidence and
natural course of inflammatory bowel disease in Korea, 2006-2012: a
nationwide population-based study. Inflammatory bowel diseases. 2015; 21:
623-30.
13. Yang SK, Yun S, Kim JH, Park JY, Kim HY, Kim YH, et al. Epidemiology of
inflammatory bowel disease in the Songpa-Kangdong district, Seoul, Korea,
1986-2005: a KASID study. Inflammatory bowel diseases. 2008; 14: 542-9.
14. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of
classifying prognostic comorbidity in longitudinal studies: development and
validation. Journal of chronic diseases. 1987; 40: 373-83.
15. Sundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA. New
ICD-10 version of the Charlson comorbidity index predicted in-hospital
mortality. Journal of clinical epidemiology. 2004; 57: 1288-94.
16. Abdul Khalek FJ, Gallicano GI, Mishra L. Colon cancer stem cells.
Gastrointestinal cancer research : GCR. 2010;: S16-23.
17. Guimaraes RM, Rocha PG, Muzi CD, Ramos Rde S. Increase income and
mortality of colorrectal cancer in Brazil, 2001-2009. Arquivos de
gastroenterologia. 2013; 50: 64-9.
18. Qin M, Ma LQ, Tan J, Chen YR, Zhu LR, Lin R, et al. Risk factors for colorectal
neoplasms based on colonoscopy and pathological diagnoses of Chinese
citizens: a multicenter, case-control study. International journal of colorectal
disease. 2015; 30: 353-61.
19. Karlen P, Lofberg R, Brostrom O, Leijonmarck CE, Hellers G, Persson PG.
Increased risk of cancer in ulcerative colitis: a population-based cohort study.
The American journal of gastroenterology. 1999; 94: 1047-52.
20. Lakatos L, Mester G, Erdelyi Z, David G, Pandur T, Balogh M, et al. Risk
factors for ulcerative colitis-associated colorectal cancer in a Hungarian cohort
of patients with ulcerative colitis: results of a population-based study.
Inflammatory bowel diseases. 2006; 12: 205-11.
21. Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative
colitis: a meta-analysis. Gut. 2001; 48: 526-35.
22. Kim BJ, Yang SK, Kim JS, Jeen YT, Choi H, Han DS, et al. Trends of ulcerative
colitis-associated colorectal cancer in Korea: A KASID study. Journal of
gastroenterology and hepatology. 2009; 24: 667-71.
23. Perdue DG, Perkins C, Jackson-Thompson J, Coughlin SS, Ahmed F,
Haverkamp DS, et al. Regional differences in colorectal cancer incidence,
stage, and subsite among American Indians and Alaska Natives, 1999-2004.
Cancer. 2008; 113: 1179-90.
24. Kramer HU, Schottker B, Raum E, Brenner H. Type 2 diabetes mellitus and
colorectal cancer: meta-analysis on sex-specific differences. European journal
of cancer. 2012; 48: 1269-82.
25. NHIS. National Health Screening Statistical Yearbook 2013. 2014.
26. Greenstein AJ, Gennuso R, Sachar DB, Heimann T, Smith H, Janowitz HD, et
al. Extraintestinal cancers in inflammatory bowel disease. Cancer. 1985; 56:
2914-21.
27. Mir-Madjlessi SH, Farmer RG, Easley KA, Beck GJ. Colorectal and extracolonic
malignancy in ulcerative colitis. Cancer. 1986; 58: 1569-74.
28. Ekbom A, Helmick C, Zack M, Adami HO. Extracolonic malignancies in
inflammatory bowel disease. Cancer. 1991; 67: 2015-9.
29. Mellemkjaer L, Olsen JH, Frisch M, Johansen C, Gridley G, McLaughlin JK.
Cancer in patients with ulcerative colitis. International journal of cancer
Journal international du cancer. 1995; 60: 330-3.
30. Bernstein CN, Blanchard JF, Kliewer E, Wajda A. Cancer risk in patients with
inflammatory bowel disease: a population-based study. Cancer. 2001; 91:
854-62.
31. Palli D, Trallori G, Bagnoli S, Saieva C, Tarantino O, Ceroti M, et al. Hodgkin's
disease risk is increased in patients with ulcerative colitis. Gastroenterology.
2000; 119: 647-53.
32. Nuako KW, Ahlquist DA, Mahoney DW, Schaid DJ, Siems DM, Lindor NM.
Familial predisposition for colorectal cancer in chronic ulcerative colitis: a
case-control study. Gastroenterology. 1998; 115: 1079-83.

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