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Doctoral Thesis in Medicine
Cancer Risk and Mortality in Adults with Intellectual Disability
Graduate School of Ajou University Department of Medicine
Hyun Jung Lee
Cancer Risk and Mortality in Adults with Intellectual Disability
Shin-Young Yim, Advisor
I submit this thesis as the Doctoral thesis in Medicine.
August, 2021
The Doctoral thesis of Hyun Jung Lee in the Graduate School of Ajou University, Department of Medicine is hereby approved.
Thesis Defense Committee Chair
Ueon Woo Rah Seal Member Bo Young Hong Seal Member Seon-Yong Jeong Seal Member Da Eun Jung Seal Member Shin-Young Yim Seal
Graduate School of Ajou University
21th June, 2021
감사의 글
제가 박사 과정을 마무리 하기까지 도움을 주신 많은 분들께 이 지면을 빌어 감사 의 인사를 전하려 합니다. 우선 지도 교수님이신 임신영 교수님의 사려 깊은 조언 과 헌신에 감사드립니다. 전공의 수련 시절에서부터 박사학위를 받기까지 오랜 시 간 저를 지도해 주시며 연구자로서의 마음가짐과 연구 기술을 익힐 수 있도록 격려 해 주셨습니다. 전공의 시절부터의 생각을 떠올려 보니, 도움과 격려가 필요한 모든 자리에 인자한 버팀목으로 서 계셨던 이일영 교수님과 재활의학도로서의 초석을 닦 을 수 있도록 지도편달을 아끼지 않으셨던 나은우 교수님, 윤승현 교수님께도 감사 의 인사를 올리고 싶습니다. 그리고 이 박사학위 논문에 관하여 귀한 조언을 해주 시고 인준을 허락해주신 정다은 교수님, 정선용 교수님, 홍보영 교수님께도 감사의 말씀을 올립니다. 본 연구 진행 과정에 있어 아낌없는 조언과 함께 많은 도움을 주 었던 동료 윤덕용 교수, 구예령 선생님, 이은영 선생님께도 감사의 마음을 전합니 다. 마지막으로 박사학위를 받는 지금의 시간까지 저를 믿고 지지해주신 부모님께 진심으로 고맙고 사랑한다는 인사를 올립니다. 감사의 마음을 전하고픈 이 모든 분 들이 오랜 시간 묵묵히 지켜봐 주며 보이는 곳에서 보이지 않는 곳에서 늘 저를 믿 고 지지해주었기에 지금 이 글을 쓸 수 있는 것이라 생각합니다. 더 멋진 연구자로 계속 성장해 나가겠다는 다짐으로 그 지지해준 마음에 답해 나가겠습니다. 격려와 응원과 도움을 주었던 내 가족들, 친구들, 동료들, 스승님들 모두에게 다시 한번 진 심으로 감사합니다.
ABSTRACT
Background: While life expectancy is continually increasing for people with intellectual disability (ID), there is limited research on cancer risk in adults with ID. Therefore, this study investigated the cancer risk in adults with ID.
Method: This retrospective propensity score-matched cohort study was conducted using data from the Korean National Health Insurance Service-National Health Information Database for the period 2007-2018. The study had two groups: the ID group and the control group.
Participants in ID group a) were newly registered with ID in the national disability registration system in 2007 or b) had at least two claims per year with ID-related disease codes in 2007.
For the control group, propensity-score matching was used for sex, age, residence, and insurance type. There were 8,187 total participants (2,729 in the ID group and 5,458 in the control group). Cancer incidence was investigated. Follow-up began on January 1, 2010 and ended either on the participant’s death or 31 December 2018 whichever occurred first.
Statistics: A Chi-square test was used to compare the sex, age, residence, insurance type and comorbidities between 2 groups. Cancer incidence and mortality were calculated.
The Cox-proportional hazards multivariate regression was used to calculate hazard ratio (HR) for cancer risk and mortality in both groups. An independent-samples t-test was conducted to compare the total number of days of outpatient visits and hospitalization between the ID group and control group.
Results: The incidence of cancer was 8.36 cases per 1,000 person-years in the ID group and 12.58 cases in the control group. After adjusting for covariate factors, the cancer risk was significantly lower in the ID group (adjusted HR, 0.68; 95% CI, 0.58-0.81). Furthermore, total number of days of outpatient visits were significantly lower in the ID group than the control group (mean ± standard deviation, 59.3 ± 85.6 vs. 65.0 ± 81.0). The mortality risk was significantly higher in the ID group (adjusted HR, 1.84; 95% CI, 1.65-2.04).
Conclusions: The findings suggested that the cancer risk in the ID group was significantly lower, compared to the control group; further research is required to understand the reason for the lower cancer risk in the ID group. The total number of days of outpatient visits was lower in the ID group and the mortality rate was high. Therefore, systematic health management policies are necessary for the health of the ID group.
Keywords: intellectual disability, cancer risk, cohort study, National Health Insurance Service-National Health Information Database, mortality, healthcare use status
Table of Contents
I. INTRODUCTION ··· 1
II. METHODS ··· 3
A. Study design ··· 3
B. The NHIS-NHID ··· 3
C. Study Population ··· 3
D. Explanatory variables ··· 5
E. Outcome definition ··· 5
F. Statistical analysis ··· 5
III. RESULTS ··· 7
A. Participant characteristics ··· 7
B. Incidence of cancer ··· 10
C. Hazard ratio (HR) of cancer from 2010 to 2018 ··· 13
D. Comparison of healthcare service use status between ID and control group from 2007 to 2009 ··· 14
E. Mortality rate and HR of death from 2010 to 2018 ··· 15
IV. DISCUSSION ··· 20
List of Tables
Table 1. Participant Characteristics ··· 8
Table 2. Participant Comorbidities ··· 9
Table 3. Incidence of Cancer in 2010-2018 ··· 11
Table 4. Hazard Ratio (HR) of Cancer ··· 13
Table 5. Comparison of Total Days of Outpatient Visit between Intellectual Disability Group and Control Group ··· 14
Table 6. Comparison of Total Days of Hospitalization between Intellectual Disability Group and Control Group ··· 14
Table 7. Participant Mortality ··· 16
Table 8. Hazard Ratio (HR) of Death ··· 18
Appendix Table A. Comparison of Incidence ratio of Cancers between the Intellectual Disability Group and Control Group ··· 27
List of Figures
Figure 1. Flow Diagram for Selection of the Study Population ··· 4 Figure 2. Comparison of Cumulative Incidence of Cancer between the Intellectual Disability Group and Control Group ··· 10 Figure 3. Comparison of Survival between Intellectual Disability Group and Control Group ··· 15
I. INTRODUCTION
Intellectual disability (ID) refers to a disability characterized by below-average intelligence and significant limitations in adaptive behavior (conceptual, social, and execution skills) that appear before the age of 18 years (1-3). The criteria for ID are having an intelligence quotient (IQ) of ≤ 70-75 and severe functional limitation appearing in at least two domains of adaptive behavior (1-3).
The prevalence of ID varies depending on the country's income (4, 5). In the United States and other countries with high incomes, it is at 1%, and in countries with low or moderate incomes, the prevalence is higher at 2% (4-6). This is because low-income countries do not have adequate prenatal screening methods, which can lead to relatively more hereditary diseases (7), as well as iodine deficiency, birth-related infections, and damage from poor maternal and child health facilities (8).
Over the past 200 years, with the improvement of hygiene awareness, the development of medical care and social welfare, the life expectancy of the general population worldwide has increased around the age of 80 in many developed countries (9). In the case of Korea, life expectancy started to increase later than in other developed countries but increased faster than any other country, and in 2015 it was 82.1 years old (9). As in the general population, life expectancy of people with ID has increased rapidly (10, 11). In the 1930s, the average age of death for people with ID was about 19 but increased to 66 in the 1990s (11). Also, several other studies have shown that the average age of death for people with ID is similar to the general population, and in particular, the life expectancy of people with Down syndrome has also increased (12-14).
As a result, interest in health promotion, social cost, and healthy aging for people with ID is increasing (15). According to the World Health Organization (WHO), active aging is “the process of optimizing opportunities for health, participation, and security over one’s lifetime to enhance the quality of life as people age,”(16, 17). As the aging population gradually increases, the demand for active aging will increase among people with ID.
Cancer is one of the most representative age-related diseases that causes a decline in quality of life and life span (18, 19), and the number one cause of death among Koreans in 2019 (20). Similar to the general population, people with ID are more likely
to develop age-related diseases, including cancer, and some studies have reported that cancer is the leading cause of death in people with ID (21, 22). Therefore, considering the period of increasing cancer incidence, the target group was adults with ID aged 40 years or older.
In this study, as part of a fundamental study on health conditions in adults with ID, I examine the risk of cancer in adults with ID. In most countries, the use of healthcare services by people with ID is lower compared to the general population, with significant barriers in accessing healthcare services (23, 24). Therefore, this study intends to compare the medical use and mortality rates of adults with ID and the general population concerning medical accessibility to assess the effects on cancer risk in adults with ID.
To the best of our knowledge, there are no studies assessing cancer risk among adults with ID in South Korea. Accordingly, this study aims to investigate cancer risk in adults with ID as part of our fundamental research for healthy aging in adults with ID using the National Health Insurance Service-National Health Information Database (NHIS-NHID).
II. METHODS
A. Study design
This retrospective propensity score-matched cohort study was conducted using the information in the NHIS-NHID from 1 January 2007 to 31 December 2018. The present study received a review exemption from the Institutional Review Board of Ajou University Hospital (AJIRB-SBR-EXP-19-503). Because the present study used non-personally identifiable data, the requirement for participant consent was waived.
B. The NHIS-NHID
The NHIS-NHID is a public database containing information on health care utilization, health screening, socio-demographic variables, and mortality rates for the South Korean population. The National Health Insurance System manages all medical expenses between beneficiaries, health care providers, and the government. Since it was first implemented for over 5 million employees in 1977, it has expanded the scope of the qualifying population in a relatively short period (25). Currently, 97% of Koreans are registered in the National Health Insurance System, and the remaining 3% of the population are registered in the medical aid system owing to low-income. The health care use database includes information on records on inpatient and outpatient usage like prescription records. The Korean standard classification of disease (KCD) based on the International Classification of Disease is used as the diagnosis code in the NHIS-NHID.
C. Study population
The inclusion criteria for the ID group were as follows: (1) participants who were newly registered with ID in the national disability registration system between January 1, 2007, and December 31, 2007, or (2) participants with an ID-related disease code (KCD codes F70-F79.9) appearing at least twice as the main or sub disease code between January 1, 2007, and December 31, 2007. The exclusion criteria were as follows: (1) participants with a diagnostic code for cancer (KCD codes C00-C97) between January 1, 2007, and December 31, 2009, were considered to already have cancer and were excluded; (2) people who died between January 1, 2007, and December 31, 2009; (3) all participants aged <40 years; (4) participant’s data related to
age and residence were omitted. For the control group, propensity score matching was used to match the age, sex, residence, and insurance type. We selected two participants per each one participant with ID. Based on these criteria, 2,279 participants in the ID group and 5,458 participants in the control group were enrolled to create a nine-year cohort observed from January 1, 2010, to December 31, 2018 (Figure 1).
Figure 1. Flow Diagram for Selection of the Study Population
NHIS-NHID = National Health Insurance Service-National Health Information Database
D. Explanatory variables
Detailed information about the participant’s sex, age, residence, insurance type, death, and comorbidities were obtained from the NHIS-NHID. Age was calculated as the mean age ± standard deviation and divided into five groups: 40-49, 50-59, 60-69, 70-79, and
≥ 80 years. Insurance type was divided into healthcare insurance where people pay the insurance premium based on income and medical aid recipients who do not pay insurance premium due to low income. Residence was defined by dividing the urban area including Seoul and other metropolitan cities and rural areas including other local provinces. Comorbidities were analyzed based on the definition of at least one claim filed between January 1, 2007, and December 31, 2009, for diabetes (KCD codes E10-14), hypertension (KCD codes I10-I15), chronic obstructive pulmonary disease (COPD) (KCD codesJ44), chronic kidney disease (CKD) (KCD code N18), dyslipidemia (KCD code E78), stroke (KCD codes I60-I64), or chromosomal abnormality (KCD codes Q90-Q99). Hospitalization days and outpatient visit days excluding psychiatry from January 1, 2007, to December 31, 2009, were investigated to compare the healthcare service use status between the ID and control groups.
E. Outcome definition
Incidence of cancer was the primary outcome of interest. Cancer was defined as claims made at least once with KCD codes C00-C97 as the main or sub disease code.
Follow-up began on January 1, 2010 and ended on either the participant’s date of death or the last date of the study period (December 31, 2018), whichever occurred first.
F. Statistical analysis
Chi-squared tests were performed to compare the proportions of categorical variables between the ID and control groups. Incidence of cancer was calculated by dividing the number of cancer cases by 1,000 person-years at risk. Cox proportional risk regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) to investigate the risk of cancer and mortality by considering explanatory factors, such as sex, age, residence, insurance type, and comorbidities in ID and control groups. After performing univariate Cox analysis with each variable, multivariate Cox analysis was performed using significant variables with p<0.05. Independent t-test was performed to compare the mean values of the total number of days of outpatient visits and
hospitalization between the ID and control groups. Moreover, the cumulative incidence for cancer between the ID and control groups was plotted. The mortality rate was calculated by dividing the number of deaths by 1,000 person-years. All statistical analyses were performed using the SAS system, version 9.4 (SAS Institute Inc., Cary, NC, USA), with a significance level set p-value< 0.05.
III. RESULTS
A. Participant characteristics
The propensity score-matched cohort had 8,187 individuals total, 2,729 were in the ID group and 5,458 were allocated to the control group. The demographic characteristics of each group are given in Table 1. There were no significant differences in sex, age group, insurance type, and residence between the ID and control groups, indicating the two groups were well-matched. The mean age of the ID group was 51.9 years (standard deviation (SD) = 9.7) and the control group was 52.1 years (SD = 9.8). The number of deaths was significantly higher in the ID group, 23.23% in the ID group and 13.96% in the control group. The mean age of death in the ID group was 65.5 (SD = 11.8) and the control group was 67.6 (SD = 12.6). Hypertension, dyslipidemia and CKD were significantly lower in the ID group than the control group (33.0% vs. 35.2%; p = 0.046, 24.5% vs. 29.0%; p < 0.0001, 0.9% vs. 1.7%; p = 0.003). Stroke and chromosomal abnormality was significantly higher in the ID group than the control group (13.1% vs. 7.1%; p <0.0001, 0.4% vs 0.0%; p = 0.001). Diabetes and COPD were not significantly different between the two groups (Table 2).
Table 1. Participant Characteristics
a Not estimable
SD = Standard deviation Characteristics
Group
p-value Control
(N=5,458) Intellectual disability (N=2,729)
Sex 0.969
Male 2,982 (54.6%) 1,493 (54.7%)
Female 2,476 (45.4%) 1,236 (45.3%)
Age (years, mean±SD) 52.1 ± 9.8 51.9 ± 9.7 0.292
Number of participants by age _a
40-49 years 2,718 (49.8%) 1,361 (49.9%)
50-59 years 1,656 (30.3%) 826 (30.3%)
60-69 years 716 (13.1%) 358 (13.1%)
70-79 years 318 (5.8%) 159 (5.8%)
≥80 years 50 (0.9%) 25 (0.9%)
Residence 0.276
Urban 1,722 (31.6%) 828 (30.3%)
Rural 3,736 (68.4%) 1,901 (69.7%)
Insurance type _a
Healthcare insurance 2,974 (54.5%) 1,487 (54.5%)
Medical aid 2,484 (45.5%) 1,242 (45.5%)
Number of deaths in 2010-2018 762 (13.96%) 634 (23.23%) <0.0001 Age at death (years, mean±SD) 67.6 ± 12.6 65.5 ± 11.8 0.001
Table 2. Participant Comorbidities Number of participants for comorbidities
Group
p-value Control
(N=5,458) Intellectual disability (N=2,729)
Diabetes 0.963
No 4,220 (77.3%) 2,108 (77.2%)
Yes 1,238 (22.7%) 621 (22.8%)
Hypertension 0.046
No 3,535 (64.8%) 1,829 (67.0%)
Yes 1,923 (35.2%) 900 (33.0%)
Dyslipidemia <0.0001
No 3,874 (71.0%) 2,061 (75.5%)
Yes 1,584 (29.0%) 668 (24.5%)
Chronic obstructive
pulmonary disease 0.253
No 5,181 (94.9%) 2,607 (95.5%)
Yes 277 (5.1%) 122 (4.5%)
Chronic kidney disease 0.003
No 5,363 (98.3%) 2,705 (99.1%)
Yes 95 (1.7%) 24 (0.9%)
Stroke <0.0001
No 5,072 (92.9%) 2,371 (86.9%)
Yes 386 (7.1%) 358 (13.1%)
Chromosomal abnormality 0.001
No 5,456 (100.0%) 2,719 (99.6%)
Yes 2 (0.0%) 10 (0.4%)
B. Incidence of cancer
Incidence of cancer in the ID group was significantly lower with an unadjusted HR of 0.66 (CI 0.56-0.79) (Figure 2). The incidence of cancer was 8.36 and 12.58 cases per 1,000 person-years in the ID and control groups, 12.51 and 9.71 cases per 1,000 person-years in men and women, respectively. Depending on the age group, cancer incidence gradually increased to 6.70 in the 40s age group, 13.14 in the 50s age group, 18.88 in the 60s age group, and 28.11 in the 70s age group, and it decreased to 24.03 in the 80s age group. For residence, the urban area was 10.83 and the rural area was 11.38, therefore the incidence rate was higher in the rural area, and there was no significant difference depending on insurance type (Table 3). Among the 729 cancer cases in this study, stomach cancer was the most common cancer in the ID group, followed by liver, colorectal, lung, prostate
,
thyroid, and breast cancer. The most common cancer in the control group was also gastric and lung cancer, followed by liver, colorectal, thyroid, and prostate cancer. (Appendix Table A).Table 3. Incidence of Cancer in 2010-2018
Variables Number of
participants
Number of participants with newly
developed cancer
Incidence (1,000
Person-Years) p-value
Group <0.0001
Control 5,458 552 12.58
Intellectual disability 2,729 177 8.36
Sex <0.0001
Male 4,475 436 12.51
Female 3,712 293 9.71
Number of participants by
age <0.0001
40-49 years 4,079 229 6.70
50-59 years 2,482 257 13.14
60-69 years 1,074 150 18.88
70-79 years 477 85 28.11
≥80 years 75 8 24.03
Insurance type 0.752
Healthcare insurance 4,461 408 11.31
Medical aid 3,726 321 11.07
Residence 0.535
Urban 2,550 220 10.83
Rural 5,637 509 11.38
Diabetes 0.002
No 6,328 538 10.54
Yes 1,859 191 13.65
Hypertension 0.002
No 5,364 427 9.75
Yes 2,823 302 14.21
Dyslipidemia 0.0008
No 5,935 493 10.37
Yes 2,252 236 13.48
Stroke 0.505
No 7,443 667 11.13
Yes 744 62 12.08
Variables Number of participants
Number of participants with newly
developed cancer
Incidence (1,000
Person-Years) p-value Chronic Obstructive
Pulmonary Disease <0.0001
No 7,788 673 10.81
Yes 399 56 19.91
Chronic Kidney Disease 0.249
No 8,068 717 11.16
Yes 119 12 15.44
C. Hazard ratio (HR) of cancer from 2010 to 2018
The risk of cancer decreased among the ID group (adjusted HR 0.68, CI 0.58-0.81) after adjustment for sociodemographic factors (sex, age group) and comorbidities (diabetes, hypertension, dyslipidemia, COPD). The risk of cancer increased with age (Age 50-59:
adjusted HR 1.93; CI 1.61-2.31, Age 60-69: adjusted HR 2.79; CI 2.25-3.46, Age 70-79:
HR 4.22; CI 3.24-5.50, Age ≥80: HR 3.85; CI 1.89-7.83), diabetes, hypertension, hyperlipidemia, and COPD did not significantly affect the cancer risk (Table 4).
Table 4. Hazard Ratio (HR) of Cancer
a Adjusted for sociodemographic factors (i.e., sex and age) and comorbidities (i.e., diabetes, hypertension, dyslipidemia and chronic obstructive pulmonary disease)
CI = Confidence interval
Variables HR(95% CI) HR(95% CI)
Unadjusted Adjusteda Group
Control 1[Reference] 1[Reference]
Intellectual disability 0.66(0.56-0.79) 0.68(0.58-0.81) Sex
Male 1[Reference] 1[Reference]
Female 0.78(0.67-0.90) 0.70(0.60-0.81)
Number of participants by age
40-49 years 1[Reference] 1[Reference]
50-59 years 1.96(1.64-2.35) 1.93(1.61-2.31)
60-69 years 2.83(2.30-3.47) 2.79(2.25-3.46)
70-79 years 4.27(3.33-5.48) 4.22(3.24-5.50)
≥80 years 3.69(1.82-7.47) 3.85(1.89-7.83)
Diabetes
No 1[Reference] 1[Reference]
Yes 1.30(1.10-1.53) 1.00(0.83-1.20)
Hypertension
No 1[Reference] 1[Reference]
Yes 1.46(1.26-1.70) 1.03(0.87-1.22)
Dyslipidemia
No 1[Reference] 1[Reference]
Yes 1.30(1.12-1.52) 1.10(0.93-1.31)
Chronic Obstructive Pulmonary Disease
No 1[Reference] 1[Reference]
Yes 1.85(1.41-2.43) 1.30(0.98-1.71)
D. Comparison of healthcare service use status between ID and control group from 2007 to 2009 Among the total days of medical use, the total number of days of outpatient visit was significantly lower in the ID group than in the control group (p=0.005) (Table 5).
In particular, in the 50-59 years and 60-69 years age groups, the total number of days of outpatient visits was significantly lower in the ID group. On the other hand, the total number of days of hospitalization was significantly higher than that of the control group (p<0.0001) (Table 6).
Table 5. Comparison of Total Days of Outpatient Visit between Intellectual Disability Group and Control Group
SD = Standard deviation
Table 6. Comparison of Total Days of Hospitalization between Intellectual Disability Group and Control Group
Age of participants Total days of outpatient visit, mean (SD)
t-value p-value Intellectual disability
group Control group
40-49 years (n= 3885) 51.9 (74.7) 49.8 (71.4) -0.86 0.388 50-59 years (n= 2387) 58.6 (89.4) 70.5 (81.2) 3.13 0.002 60-69 years (n= 1043) 72.9 (97.3) 87.1 (82.2) 2.34 0.020 70-79 years (n= 474) 91.4 (111.1) 110.5 (111.3) 1.76 0.079
≥80 years (n= 74) 79.4 (72.8) 80.7 (95.1) 0.06 0.956
Total (n= 7863) 59.3 (85.6) 65.0 (81.0) 2.8 0.005
Total days of hospitalization, mean (SD)
E. Mortality rate and HR of death from 2010 to 2018
The mortality rate between the two groups was 29.23 per 1,000 persons in the ID group and 16.69 in the control group (Figure 3). Men had a higher mortality rate of 25.64 and women 15.05, with an increase by age group. Also, the mortality rate was higher in the case of medical aid recipients and those with comorbid diseases, and rural over urban areas (Table 7). The mortality risk increased in the ID group (adjusted HR 1.84, CI 1.65-2.04), among men (adjusted HR of female 0.47, CI 0.42-0.53), with age (Age 50-59: adjusted HR 1.74; CI 1.52-2.01, Age 60-69: adjusted HR 3.22; CI 2.74-3.78, Age 70-79: HR 8.18; CI 6.86-9.77, Age ≥80: HR 23.32; CI 17.61-30.89), and medical aid (adjusted HR 1.80, CI 1.61-2.00). Most comorbidities increased the mortality risk, but in the case of hyperlipidemia, the mortality risk was lower (adjusted HR 0.81, CI 0.72-0.92) (Table 8).
Figure 3. Comparison of Survival between Intellectual Disability Group and Control Group
Table 7. Participant Mortality
Variables Number of
participants Number of
deaths Mortality
(1,000 Person-Years) p-value
Group <0.0001
Control 5,458 762 16.69
Intellectual disability 2,729 634 29.23
Sex <0.0001
Male 4,475 926 25.64
Female 3,712 470 15.05
Number of participants by
age <0.0001
40-49 years 4,079 366 10.47
50-59 years 2,482 413 20.23
60-69 years 1,074 297 35.22
70-79 years 477 256 79.60
≥80 years 75 64 190.87
Insurance <0.0001
Healthcare insurance 4,461 605 16.17
Medical aid 3,726 791 26.42
Residence <0.0001
Urban 2550 413 19.62
Rural 5637 983 21.23
Diabetes <0.0001
No 6,328 902 17.10
Yes 1,859 494 33.83
Hypertension <0.0001
Variables Number of
participants Number of
deaths Mortality
(1,000 Person-Years) p-value
No 7,788 1261 19.58
Yes 399 135 45.53
Chronic kidney disease <0.0001
No 8,068 1344 20.20
Yes 119 52 64.14
Chromosomal abnormality 0.0004
No 8.175 1391 21.88
Yes 12 5 60.24
Table 8. Hazard Ratio (HR) of Death
Variables HR (95% CI) HR (95% CI)
Unadjusted Adjusteda
Group
Control 1[Reference] 1[Reference]
Intellectual disability 1.76(1.59-1.96) 1.84(1.65-2.04) Sex
Male 1[Reference] 1[Reference]
Female 0.58(0.52-0.65) 0.47(0.42-0.53)
Number of participants by age
40-49 years 1[Reference] 1[Reference]
50-59 years 1.93(1.68-2.22) 1.74(1.51-2.01)
60-69 years 3.41(2.93-3.98) 3.22(2.74-3.78)
70-79 years 8.09(6.89-9.49) 8.18(6.86-9.77)
≥80 years 20.89(16.00-27.28) 23.32(17.61-30.89)
Insurance type
Healthcare insurance 1[Reference] 1[Reference]
Medical aid 1.07(0.95-1.21) 1.80(1.61-2.00)
Residence
Urban 1[Reference] 1[Reference]
Rural 1.08(0.97-1.22) 1.00(0.89-1.13)
Diabetes
No 1[Reference] 1[Reference]
Yes 2.01(1.80-2.24) 1.35(1.19-1.53)
Hypertension
a Adjusted for sociodemographic factors (i.e., sex and age) and comorbidities (i.e., diabetes, hypertension, dyslipidemia, stroke, chronic obstructive pulmonary disease, chronic kidney disease and chromosomal abnormality)
CI = Confidence interval
Variables HR (95% CI) HR (95% CI)
Unadjusted Adjusteda
No 1[Reference] 1[Reference]
Yes 2.40(2.01-2.87) 1.32(1.10-1.59)
Chronic kidney disease
No 1[Reference] 1[Reference]
Yes 3.28(2.49-4.33) 2.14(1.61-2.85)
Chromosomal abnormality
No 1[Reference] 1[Reference]
Yes 2.69(1.12-6.46) 3.95(1.63-9.55)
IV. DISCUSSION
This study was the first nationwide retrospective cohort study in South Korea to examine associations of cancer risk in adults with ID. This study found that the ID group showed a lower risk of cancer than the control group with an adjusted HR of 0.68 (95% CI; 0.56-0.79). The risk factors for cancer were being a man and old age.
According to the research on cancer incidence in people with ID, some studies showed no significant difference in cancer risk compared to the general population (22, 26, 27), and others showed a low cancer risk (28, 29). Studies in which cancer incidence is comparable to that of the general population included children. Therefore, there were fewer adult subjects compared to this study. On the other hand, according to a study by Satgé et al., the risk of cancer in adults with ID over 55 years of age was lower than the general population and similar to the results of this study (28). The reason being was that in Satgé et al.’s study all people with ID aged 55 years and over registered in the Swedish national record were targeted, hence the selection of the target group was similar to the present study. However, previous studies only compared cancer incidence, and no cancer risk study comprehensively considered healthcare service use or mortality. Healthcare use varies by country, and cancer detection can be affected by healthcare use and mortality. Therefore, this study targeted adults with ID aged 40 years and over in South Korea and compared the mortality rate and healthcare use status between adults with ID and the control group.
The reason for the low risk of cancer was twofold. First, if the healthcare service use is low, the risk of cancer may be low because it has not been detected even if it is present. It is difficult for people with ID to be aware of health problems, and even if
ID, even if the hospitalization period is long, cancer detection may be small. Previous studies have also found that people with ID often use medical services after profound disease progression or miss treatment periods due to minimal access to health services and preventative screening (23, 24, 31-34), which often leads to death when they go to the hospital (35).
In Korea, early cancer detection is mostly done through health checkups (36, 37), however, people with ID are less likely to have jobs (38, 39). People with jobs often experience early diagnosis of diseases through life-cycle health checkups. Although the health checkup rate among people with ID gradually increased from 42.5% in 2002 to 72.26% in 2018, the health checkup rate is still lower compared to the general population (40, 41).
Second, the mortality rate of people with ID under aged 40 is high. People with ID have delayed response in risk recognition, making the mortality rate from accidents such as fires, falls, and traffic accidents is high (42, 43). In addition, people with severe ID are known to have a reduced life expectancy at any age due to more severe related disabilities and neurological deficits, including genetic and biological associations (44-49). In this study, the mortality rate of the ID group was twice as high as that of the control group. Cancer is among the senile diseases, increasing with age (18, 50), thus, for a group with a lower life expectancy, the risk of cancer can be considered low. In previous studies, the causes of mortality in people with ID were central nervous system disease associated with ID or infectious diseases, such as urinary tract infection and respiratory tract infection (35, 51). Moreover, a study by Heslop et al. found that when better healthcare services were provided, potentially avoidable deaths reached 37%, suggesting that adequate health care can reduce the mortality rate (52). Therefore, since the mortality rate of people with ID is high due to diseases or accidents other than cancer, even if cancer was present at the time of death, it is possible that these patients died without its detection. Therefore, these findings suggest that access to health checkups and primary medical care services should be improved to detect cancer or other comorbidities early in adults with ID in Korea.
In this regard, it is necessary to educate caregivers to be more aware of the early signs of health problems of people with ID, including how people with ID individually express their health problems. In addition, policy development is necessary so that people with ID can receive health checkups for each life cycle. Higher use of primary medical care for people with ID will enable early detection of cancer as well as other comorbidities,
improving such individuals’ health conditions and consequently improving their quality of life and life expectancy. However, there is still a possibility that the cancer risk may be lower in adults with ID genetically or immunologically, even after considering medical access and mortality. Therefore, further research is needed to understand the reason or mechanism for lower cancer risk in adults with ID.
This study has several strengths. First, to the best of our knowledge, this was the first study exploring the association between adults with ID and cancer risk in Korea.
Second, the study target group included the newly registered persons with ID in the national disability registration system, comprehensively representing people older than 40 years with low cognitive function, including neurodevelopmental disorders and neurocognitive disorders. Third, the nine-year follow-up period from 2010 to 2018 was a long follow-up period that was not common in previous studies. Finally, the NHIS-NHID's cancer claim data do not appear to differ significantly from the cancer incidence rate by age as indicated by the Cancer Registration Headquarters (53), and the records of death in the NHIS-NHID were linked with South Korea’s national vital statistics; therefore, the reliability of this study is high.
This study also had limitations. First, although the selection bias between the ID group and the control group was resolved through propensity score matching, there may still be unmeasured confounding variables. Second, lifestyle variables such as smoking, drinking, and exercise habits that may affect cancer development were not included in the study; further, a risk analysis according to cancer type was not performed. Third, since data from the national disability registration database was used and participants newly registered as ID were included, it was not possible to distinguish between ID that occurred before the age of 18 or in adulthood. However, it represents adults with low cognitive function under the level of IQ 70, for whatever reason. It is thought that the
V. CONCLUSION
The cancer risk in adults with ID was lower than that of adults in the control group.
Outpatient visit use was lower in the ID group, and the mortality rate was higher.
Therefore, to lower the mortality rate and increase the detection of cancer in adults with ID, it is necessary to improve caregiver health awareness and medical policies for adults with ID to increase access to primary care. Moreover, further research is needed to understand the reason for the low cancer risk in the ID group.
REFERENCES
1. Schalock RL, Borthwick-Duffy SA, Bradley VJ, Buntinx WH, Coulter DL, Craig EM, et al. Intellectual disability: Definition, classification, and systems of supports:
ERIC; 2010.
2. Harris JC. Intellectual disability: Understanding its development, causes, classification, evaluation, and treatment: Oxford University Press; 2006.
3. Luckasson R, Borthwick-Duffy S, Buntinx WH, Coulter DL, Craig EMP, Reeve A, et al. Mental retardation: Definition, classification, and systems of supports: American Association on Mental Retardation; 2002.
4. Durkin M. The epidemiology of developmental disabilities in low‐income countries. Mental retardation and developmental disabilities research reviews.
2002;8(3):206-11.
5. Maulik PK, Mascarenhas MN, Mathers CD, Dua T, Saxena S. Prevalence of intellectual disability: a meta-analysis of population-based studies. Research in developmental disabilities. 2011;32(2):419-36.
6. Yim SY, Yu HH, Lee IY. The prevalence of mental retardation among third grade elementary school children in the Suwon area, Korea. Journal of Korean medical science. 2002;17(1):86.
7. Dave U, Shetty N, Mehta L. A community genetics approach to population screening in India for mental retardation—a model for developing countries. Annals of human biology. 2005;32(2):195-203.
8. Kuo-Tai T. Mentally retarded persons in the People's Republic of China: review of epidemiological studies and services. American Journal on Mental Retardation. 1988.
9. Roser M, Ortiz-Ospina E, Ritchie H. Life expectancy. Our World in Data. 2013.
13. Glasson EJ, Sullivan SG, Hussain R, Petterson B, Montgomery PD, Bittles AH.
The changing survival profile of people with Down's syndrome: implications for genetic counselling. Clinical genetics. 2002;62(5):390-3.
14. Bittles A, Glasson E. Clinical, social, and ethical implications of changing life expectancy in Down syndrome. Developmental medicine and child neurology.
2004;46(4):282.
15. Hogg J, Lucchino R, Wang K, Janicki M. Healthy ageing–adults with intellectual disabilities: ageing and social policy. Journal of Applied Research in Intellectual Disabilities. 2001;14(3):229-55.
16. Fernández-Ballesteros R, Robine JM, Walker A, Kalache A. Active aging: a global goal. Hindawi; 2013.
17. World Health Organization. Active ageing: A policy framework: World Health Organization. Noncommunicable Disease Prevention and Health Promotion Department.
2002.
18. Balducci L, Aapro M. Epidemiology of cancer and aging. Biological Basis of Geriatric Oncology: Springer; 2005. p. 1-15.
19. Pedersen JK, Engholm G, Skytthe A, Christensen K, Research AoGC. Cancer and aging: Epidemiology and methodological challenges. Acta Oncologica.
2016;55(sup1):7-12.
20. Vital Statistics Division, Statistics Korea. Cause of death statistics. 2019.
21. Heslop P, Blair P, Fleming P, Hoghton M, Marriott A, Russ L. Confidential Inquiry into premature deaths of people with learning disabilities (CIPOLD). Bristol:
Norah Fry Research Centre. 2013.
22. Sullivan SG, Hussain R, Threlfall T, Bittles AH. The incidence of cancer in people with intellectual disabilities. Cancer Causes & Control. 2004;15(10):1021-5.
23. Beange H, Durvasula S. Health inequalities in people with intellectual disability:
Strategies for improvement. Health Promotion Journal of Australia: Official Journal of Australian Association of Health Promotion Professionals. 2001;11(1):27.
24. Emerson E, Hatton C. Health inequalities and people with intellectual disabilities: Cambridge University Press; 2014. 5-8 p.
25. Bae J-Y. Impacts of health insurance coverage expansion on health care utilization and health status. Korean J Soc Welf Stud. 2010;41(2):35-65.
26. Patja K, Eero P, Iivanainen M. Cancer incidence among people with intellectual disability. Journal of Intellectual Disability Research. 2001;45(4):300-7.
27. Janicki MP, Davidson P, Henderson C, McCallion P, Taets J, Force L, et al.
Health characteristics and health services utilization in older adults with intellectual disability living in community residences. Journal of Intellectual Disability Research.
2002;46(4):287-98.
28. Satgé D, Axmon A, Trétarre B, Sandberg M, Ahlström G. Cancer diagnoses among older people with intellectual disability compared with the general population: a national register study. Journal of Intellectual Disability Research. 2020.
29. Hasle H, Friedman JM, Olsen JH, Rasmussen SA. Low risk of solid tumors in persons with Down syndrome. Genetics in Medicine. 2016;18(11):1151-7.
30. Disability NCo. The Current State of Health Care for People with Disabilities.
2009.
31. Brameld K, Spilsbury K, Rosenwax L, Leonard H, Semmens J. Use of health services in the last year of life and cause of death in people with intellectual disability:
a retrospective matched cohort study. BMJ open. 2018;8(2).
32. Emerson E, Baines S, Allerton L, Welch V. Health inequalities and people with learning disabilities in the UK. 2011.
33. Taggart L, Cousins W. Health promotion for people with intellectual and developmental disabilities: McGraw-Hill Education (UK); 2014.
34. Byrne JH, Lennox NG, Ware RS. Systematic review and meta-analysis of primary healthcare interventions on health actions in people with intellectual disability.
Journal of Intellectual and Developmental Disability. 2016;41(1):66-74.
35. Hosking FJ, Carey IM, Shah SM, Harris T, DeWilde S, Beighton C, et al.
Mortality among adults with intellectual disability in England: comparisons with the general population. American Journal of Public Health. 2016;106(8):1483-90.
36. Kim Y, Jun JK, Choi KS, Lee H-Y, Park E-C. Overview of the National Cancer screening programme and the cancer screening status in Korea. Asian Pac J Cancer Prev. 2011;12(3):725-30.
Issue of Employment for Adults with an Intellectual Disability in I reland. Journal of Applied Research in Intellectual Disabilities. 2013;26(4):335-43.
40. Public Rehabilitation Medical Support Division, National Rehabilitation Center.
Health screening rate for the disabled by city, county and district, 2018. [Korean]
Avalable at: https://www.nrc.go.kr:2451/viewer/skin/doc.html?fn=20200225100216342077_
2.xlsx&rs =/viewer/result/202107/
41. Park EK. Mortality in disabled and non-disabled people depending on health screening status: Graduate School of Public Health,,Yonsei University; 2020. [Korean]
42. Greenspan S, Switzky HN, Woods GW. Intelligence involves risk-awareness and intellectual disability involves risk-unawareness: Implications of a theory of common sense. Journal of Intellectual and Developmental Disability. 2011;36(4):246-57.
43. Finlayson J, Morrison J, Jackson A, Mantry D, Cooper SA. Injuries, falls and accidents among adults with intellectual disabilities. Prospective cohort study. Journal of Intellectual Disability Research. 2010;54(11):966-80.
44. Tyrer F, Smith L, McGrother C. Mortality in adults with moderate to profound intellectual disability: a population‐based study. Journal of Intellectual Disability Research. 2007;51(7):520-7.
45. Durvasula S, Beange H, Baker W. Mortality of people with intellectual disability in northern Sydney. Journal of Intellectual and Developmental Disability.
2002;27(4):255-64.
46. Alborz A, McNally R, Swallow A, Glendinning C. From the Cradle to the Grave: A literature review of access to. 2004.
47. Arvio M, Sillanpää M. Prevalence, aetiology and comorbidity of severe and profound intellectual disability in Finland. Journal of Intellectual Disability Research.
2003;47(2):108-12.
48. Cooper S-A, McLean G, Guthrie B, McConnachie A, Mercer S, Sullivan F, et al. Multiple physical and mental health comorbidity in adults with intellectual disabilities: population-based cross-sectional analysis. BMC family practice.
2015;16(1):1-11.
49. Carey IM, Shah SM, Hosking FJ, DeWilde S, Harris T, Beighton C, et al.
Health characteristics and consultation patterns of people with intellectual disability: a cross-sectional database study in English general practice. British Journal of General Practice. 2016;66(645):e264-e70.
50. Corazziari I, Quinn M, Capocaccia R. Standard cancer patient population for age standardising survival ratios. European Journal of Cancer. 2004;40(15):2307-16.
51. Axmon A, Björkman M, Ahlström G. Hospital readmissions among older people with intellectual disability in comparison with the general population. Journal of Intellectual Disability Research. 2019;63(6):593-602.
52. Heslop P, Blair PS, Fleming P, Hoghton M, Marriott A, Russ L. The Confidential Inquiry into premature deaths of people with intellectual disabilities in the UK: a population-based study. The Lancet. 2014;383(9920):889-95.
53. Seo H. A comparison of the cancer incidence rates between KCCR’s registered cancer statistics and NHIC’s data of insurance claims [master’s thesis]. Seoul: Korea University. 2012. [Korean]
APPENDIX
Table A. Comparison of Incidence ratio of Cancers between the Intellectual Disability Group and Control Group
ID, Intellectual disability; IR, Incidence rate; CNS, Central nervous system Type of cancer ID group
(N=2,729)
(1,000 IR Person- Years)
Control group (N=5,458)
(1,000 IR Person- Years)
Total
(N=8,187) p-value
All Cancer 177 8.36 552 12.58 729 <.0001
Head and Neck 11 0.52 26 0.59 37 0.77
Oropharyngeal 9 0.43 18 0.41 27 1.00
CNS 2 0.09 8 0.18 10
Bowel 49 2.32 149 3.40 198 0.01
Esophageal 1 0.05 10 0.23 11
Stomach 24 1.13 62 1.41 86
Colorectal 18 0.85 51 1.16 69
Anal 6 0.28 26 0.59 32
Digestive system 36 1.70 91 2.07 127 0.27
Liver 20 0.95 56 1.28 76
Gall bladder &biliary 8 0.38 13 0.30 21
Pancreas 8 0.38 22 0.50 30
Lung 17 0.80 62 1.41 79
Female organs 7 0.33 21 0.48 28 0.46
Breast 9 0.43 32 0.73 41 0.17
Uterine cervix 2 0.09 3 0.07 5
Uterine body 2 0.09 8 0.18 10
Ovary 3 0.14 10 0.23 13
Prostate 11 0.52 34 0.77 45 0.27
Urinary organ 9 0.43 26 0.59 35 0.44
Kidney 5 0.24 17 0.39 22
Bladder 4 0.19 9 0.21 13
Skin 2 0.09 16 0.36 18 0.08
Thyroid 9 0.43 44 1.00 53
Hematologic system 6 0.28 20 0.46 26 0.37
Lymphoma 1 0.05 10 0.23 11
Leukemia 1 0.05 4 0.09 5
Myeloma 4 0.19 6 0.14 9
Others 11 0.52 31 0.71 42 0.67
- 국문 요약 -
성인 지적장애인에서 암 발생 위험 연구
아주대학교 대학원 의학과 이 현 정
(지도교수: 임 신 영)
배경: 지적장애인들의 기대수명은 일반인구에서와 마찬가지로 증가하여 왔다. 기 대 수명의 증가와 함께 성인 지적장애인의 건강 상태에 대한 관심 또한 높아지고 있지만 현재까지 우리나라에서 지적장애인의 암 발생 위험에 관한 연구는 거의 없는 실정이다. 따라서 본 연구는 대한민국 성인 지적장애인에서의 암 발생 위험 을 조사하고자 하였다.
방법: 2007년 1월 1일부터 2018년 12월 31일까지의 국민건강보험 국민건강정보자 료를 사용하여 후향적 성향 점수 짝짓기 코호트 연구를 수행하였다. 연구는 지적 장애군과 대조군 두 그룹으로 나누어 진행하였다. 지적장애군의 포함 기준은 1) 2007년 1월 1일부터 2007년 12월 31일까지 새롭게 지적장애로 장애 등록 되어 있 는 경우 또는 2) 같은 기간 동안 지적장애 관련 질병코드 (F70-F79.9)로 적어도 2 번 이상 청구된 경우였다. 대조군은 성별, 연령, 거주지 및 보험 유형에 대해 성향
점수 짝짓기를 사용하여 지적장애인 1명당 2명을 짝지었다. 따라서 지적장애군
2729명, 대조군 5458명으로 총 8187명이 연구 대상으로 정해졌다. 연구 종료점은 암 발생일, 사망일, 연구종료일인 2018년 12월 31일 중 먼저 발생한 날짜였다. 지
(평균 ± 표준편차, 138.9±251.8 대 51.1±143.1). 사망률은 지적장애군에서 유의하게 더 높았다 (지적장애군 29.23/1000인년, 대조군 16.69/1000인년).
결론: 연구 결과 지적장애군에서 암발생률 및 암 위험비는 대조군에 비하여 유의 하게 낮았다. 또한, 지적장애군에서 사망률이 높았으며, 외래 이용 일수가 적었다.
따라서, 성인 지적장애인의 건강상태 증진을 위해서는 일차 의료 접근성을 높이기 위한 지적장애인 보호자의 건강에 대한 인식 개선과 체계적인 의료 정책이 필요 하겠다. 또한 의료 이용 상태나 사망률을 고려하였음에도 지적장애군에서 유전적 또는 면역학적으로 암 위험이 낮을 수 있다는 가능성은 있으므로 이에 대해서는 원인이나 기전을 이해하기 위한 추가적인 연구가 필요할 것으로 보인다.
핵심어: 지적 장애, 암 위험, 코호트 연구, 국민건강보험 국민건강정보자료, 사망 률, 의료이용일수
