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