Blood Res 2021; 56(4): 301-314  https://doi.org/10.5045/br.2021.2021187
Twenty-year incidence trend of hematologic malignancies in the Republic of Korea: 1999–2018
Won-Ju Park1,2,3,#, Joo-heon Park4,#, Seunghyeon Cho1, Myung Geun Shin4
1Department of Occupational and Environmental Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 2Gwangju Jeonnam Regional Cancer Center, Hwasun, 3Jeollanamdo Public Health Policy Institute, Jeollanamdo Provincial Office, Muan, 4Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea
Correspondence to: Myung Geun Shin, M.D., Ph.D.
Won-Ju Park, M.D., Ph.D.
Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun 58128, Korea (M.G.S.)
Department of Occupational and Environmental Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun 58128, Korea (W.J.P.)
E-mail: M.G.S., mgshin@chonnam.ac.kr
W.J.P., wonjupark@jnu.ac.kr

#These authors contributed equally to this study.
Received: October 8, 2021; Revised: November 6, 2021; Accepted: November 12, 2021; Published online: December 9, 2021.
© The Korean Journal of Hematology. All rights reserved.

cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background
In this study, we presented the national cancer statistics on the incidence of hematologic malignancies in the Republic of Korea (ROK) over a period of 20 years, from 1999 to 2018.
Methods
We obtained data on the incidence of hematologic malignancies using the Korean Statistical Information Service (KOSIS). For each hematologic malignancy, the number of cases, crude incidence rate, and age-standardized incidence rate were calculated, and the statistical trends were confirmed by Poisson regression and Joinpoint regression analysis.
Results
All the investigated hematologic malignancies showed a statistically significant increase in incidence over 20 years. The 20-year trend of the age-standardized incidence rate was as follows: non-Hodgkin lymphoma [average annual percent change (AAPC)=2.26%, P-trend <0.05], leukemia (AAPC=0.94%, P-trend <0.05), myeloid leukemia (AAPC=1.44%, P-trend <0.05), multiple myeloma (AAPC=3.05%, P-trend <0.05), myeloproliferative disorders (AAPC=9.87%, P-trend <0.05), myelodysplastic syndrome (AAPC=7.59%, P-trend <0.05), malignant immunoproliferative diseases (AAPC=11.82%, P-trend <0.05), lymphoid leukemia (AAPC=2.21%, P-trend <0.05), and Hodgkin lymphoma (AAPC=4.04%, P<0.05).
Conclusion
It was confirmed that the incidence of hematologic malignancies has increased significantly in the ROK over the past 20 years. This study can be used as foundational data source for future studies. In addition, it can aid in the necessary actions of predicting future incidences and establishing future healthcare policies.
Keywords: Epidemiology, Hematologic neoplasms, Neoplasms, Registries, Statistics
INTRODUCTION

Since the national causes of death statistics were officially established in 1983, cancer has been the number one cause of death in the Republic of Korea (ROK) to date [1]. With the aging of the population, the incidence of cancer has also been increasing rapidly [2]. The Korea Central Cancer Registry (KCCR) registers cancer-related data and publishes books on cancer statistics every year. However, since the cancer statistics book mainly describes only the most common types of cancers, it is up to each researcher to analyze the statistical data of detailed cancers. This study intends to provide statistics on the incidence of hematologic malignancies over the past 20 years based on open national statistical data. The results of this study will be used as foundational data for future research and policy establishment on hematologic malignancies.

MATERIALS AND METHODS

Data collection

We obtained data on hematologic malignancies from 1999 to 2018 through the Korean Statistical Information Service (KOSIS). KOSIS is a national statistical

Malignancy classification

Hematologic malignancies were categorized according to the International Classification of Diseases for Oncology 3rd edition (ICD-O-3) [4]. For consistent comparison and convenience, these malignancies were converted to the Inter-national Classification of Diseases, 10th edition (ICD-10) [5]. Diseases not classified as malignant according to ICD-10 (myeloproliferative disorders and myelodysplastic syndromes) were referred to using ICD-O-3 codes without conversion. The classification of hematologic malignancies according to the ICD-10 was as follows: non-Hodgkin lymphoma (C82–86, C96), leukemia (C91–95), myeloid leukemia (C92–94), multiple myeloma (C90), myeloproliferative disorders (ICD-O-3 M995_/3, M996_/3, M997_/3), myelodysplastic syndrome (ICD-O-3 M9980/3, M9981/3, M9982/3, M9983/3, M9985/3, M9986/3, M9987/3, M9988/3, M9989/3), malignant immunoproliferative diseases (C88), lymphoid leukemia (C91), Hodgkin lymphoma (C81), and leukemia of unspecified cell type (C95) (Table 1).

Table 1

The classification of hematologic malignancies according to the Republic of Korea’s Cancer Control Act and Statistics Act.

AbbreviationICD-10 code (or ICD-O-3 code)
Non-Hodgkin lymphomaICD-10 C82–C86, C96Follicular lymphoma. Follicle center lymphoma. Other types of follicular lymphoma. Follicular lymphoma, unspecified. Small cell B-cell lymphoma. Mantle cell lymphoma. Diffuse large B-cell lymphoma. Lymphoblastic (diffuse) lymphoma. Burkitt lymphoma. Other non-follicular lymphoma. Non-follicular (diffuse) lymphoma, unspecified. Mature T/NK-cell lymphomas. Mycosis fungoides. Sézary disease. Peripheral T-cell lymphoma, not classified. Anaplastic large cell lymphoma. Cutaneous T-cell lymphoma, unspecified. Other mature T/NK-cell lymphomas. Mature T/NK-cell lymphomas, unspecified. Unspecified B-cell lymphoma. Mediastinal (thymic) large B-cell lymphoma. Other specified types of non-Hodgkin lymphoma. Non-Hodgkin lymphoma, unspecified. Other specified types of T/NK-cell lymphoma. Multifocal and multisystemic (disseminated) Langerhans-cell histiocytosis. Malignant mast cell neoplasm. Sarcoma of dendritic cells (accessory cells). Multifocal and unisystemic Langerhans-cell histiocytosis. Unifocal Langerhans-cell histiocytosis. Histiocytic sarcoma. Other specified.
LeukemiaICD-10 C91–95See myeloid leukemia, lymphoid leukemia, and leukemia unspecified.
Myeloid leukemiaICD-10 C92–C94Acute myeloblastic leukemia. Chronic myeloid leukemia. Myeloid sarcoma. Acute promyelocytic leukemia. Acute myelomonocytic leukemia. Acute myeloid leukemia. Other myeloid leukemia. Myeloid leukemia, unspecified. Acute monoblastic/monocytic leukemia. Chronic myelomonocytic leukemia. Juvenile myelomonocytic leukemia. Other monocytic leukemia. Monocytic leukemia, unspecified. Acute erythroid leukemia. Acute megakaryoblastic leukemia. Mast cell leukemia. Acute panmyelosis with myelofibrosis.
Multiple myelomaICD-10 C90Multiple myeloma. Plasma cell leukemia. Extramedullary plasmacytoma. Solitary plasmacytoma.
Myeloproliferative disordersICD-O-3 M995_/3, M996_/3, M997_/3Polycythemia vera. Chronic myeloproliferative disease. Essential thrombocythemia. Osteomyelofibrosis. Chronic eosinophilic leukemia.
Myelodysplastic syndromeICD-O-3 M9980/3 ∼M9983/3, M9985/3 ∼M9989/3Myelodysplastic syndromes.
Malignant immunoproliferative diseasesICD-10 C88Waldenström macroglobulinemia. Heavy chain disease. Immunoproliferative small intestinal disease. Extranodalmarginal zone B-cell lymphoma of mucosa-associated lymphoid tissue [MALT-lymphoma]. Other malignant immunoproliferative diseases. Malignant immunoproliferative disease, unspecified.
Lymphoid leukemiaICD-10 C91Acute lymphoblastic leukemia. Chronic lymphocytic leukemia of B-cell type. Prolymphocytic leukemia of B-cell type. Hairy cell leukemia. Adult T-cell lymphoma/leukemia. Prolymphocytic leukemia of T-cell type. Mature B-cell leukemia Burkitt-type. Other lymphoid leukemia. Lymphoid leukemia, unspecified.
Hodgkin lymphomaICD-10 C81Hodgkin lymphoma. Other Hodgkin lymphoma. Hodgkin lymphoma, unspecified.
Leukemia unspecifiedICD-10 C95Acute leukemia of unspecified cell type. Chronic leukemia of unspecified cell type. Leukemia, unspecified.


Statistical analysis

From the collected data, the number of incidence cases of each hematologic malignancy by year was determined. The average annual percent change (AAPC) was analyzed using the Joinpoint regression model which is a trend analysis software developed by the US National Cancer Institute [6]. This method describes changes in data trends by connecting several different line segments on a logarithmic scale at Joinpoints. Tests of significance were performed using the Monte Carlo permutation method. An AAPC for each line segment and the corresponding 95% confidence interval (CI) were estimated. The AAPC is tested to determine whether a difference exists from the null hypothesis of no change. In the final model, each Joinpoint informs a statistically significant change in trends, and each of these trends is described by an AAPC [7]. The crude incidence rate (CIR) for each year and the age-standardized incidence rate (ASR) was calculated by defining the 2000 mid-year population (the population count as of July 1, 2000) as the standard population [CIR=(the number of new patients/mid-year population) ×1,000,000]. From 1998 to 2018, each incidence rate ratio (IRR) was calculated according to the one-year increase through Poisson regression, and the 95% CI and P -value were calculated. The CIRs and ASRs were rounded to six decimal places. Poisson regression was performed by converting the number of cases per 10 million people into an integer. Poisson regression analyses were performed using SPSS (version 27.0, IBM Corp., Armonk, NY, USA), and the significance level was set at P <0.05.

RESULTS

Non-Hodgkin lymphoma

The number of newly diagnosed NHL cases increased by 148.0%, from 2,103 in 1999 to 5,216 in 2018. The AAPC in incidence cases during this period was 5.16%, and the trend was statistically significant. Within a one-year increase, the IRR increased significantly to 1.052 (95% CI, 1.051–1.054; P<0.001). The CIR per million population increased by 128.0% from 44.59 in 1999 to 101.67 in 2018. Within a one-year increase, the IRR increased significantly to 1.047 (95% CI, 1.044–1.051; P<0.001). The ASR per million population increased by 47.1% from 45.48 in 1999 to 66.88 in 2018. Within a one-year increase, the IRR increased significantly to 1.023 (95% CI, 1.019–1.026; P<0.001). The AAPC in the ASR during this period was 2.26%, and the trend was statistically significant (P<0.05) (Table 2, Fig. 1).

Table 2

The incidence case number of non-Hodgkin lymphoma and trend in crude incidence rates and age-standardized incidence rates per million population in the Republic of Korea from 1999 to 2018.

YearsN of casesCIRASRa)ASRa)
MenWomenTotalAAPC (%)AAPC (%)IRR (per yr)
19991,2528512,1035.16b)44.5896445.478512.26b)1.023b)
20001,2228162,03842.8744742.87447
20011,3329052,23746.7238545.78075
20021,3229192,24146.5655144.58582
20031,3759812,35648.7700045.65773
20041,5111,0572,56852.9644948.58076
20051,5051,0912,59653.3245347.61164
20061,6511,1212,77256.7021649.38565
20071,7411,1942,93559.7390450.59199
20081,7451,2563,00160.7432750.12326
20091,8761,3623,23865.2076452.63546
20101,9541,4293,38367.8230353.64297
20112,1101,5513,66173.0571256.72628
20122,1941,5803,77474.9622756.77698
20132,3141,6914,00579.2144657.80355
20142,4001,7134,11381.0233358.60555
20152,5601,8844,44487.2198261.06796
20162,8052,0194,82494.3791764.58155
20172,7362,0804,81694.0061363.41746
20183,0012,2155,216101.6746766.87682

a)Calculated by defining the 2000 mid-year Korean population (July 1, 2000) as the standard population. b)Statistically significant trend (P< 0.05).

Abbreviations: AAPC, average annual percent change; ASR, age-standardized incidence rate; CIR, crude incidence rate; IRR, incidence rate ratio.



Figure 1. Annual incidence of non-Hodgkin lymphoma in the Republic of Korea. Number of non-Hodgkin lymphoma cases (A). Crude and age-standardized incidence rate of non-Hodgkin lymphoma per million using the 2000 Korean standard population (B). a)Comparing 1999 and 2018. b)Average annual percent change by Joinpoint regression analysis. c)Incidence rate ratio per year from 1999 to 2018 as calculated by Poisson regression.
Abbreviations: AAPC, average annual percent change; ASR, age-standardized incidence rate; CI, confidence interval; CIR, crude incidence rate; IRR, incidence rate ratio.

Leukemia

The number of newly diagnosed leukemia cases increased by 64.5%, from 2,124 in 1999 to 3,494 in 2018. The AAPC in incidence cases during this period was 2.89%, and the trend was statistically significant. Within a one-year increase, the IRR increased significantly to 1.029 (95% CI, 1.028–1.031; P<0.001). The CIR per million population increased by 51.3% from 45.03 in 1999 to 68.11 in 2018. Within a one-year increase, the IRR increased significantly to 1.025 (95% CI, 1.021–1.028; P<0.001). The ASR per million population increased by 15.4% from 45.46 in 1999 to 52.45 in 2018. Within a one-year increase, the IRR increased significantly to 1.009 (95% CI, 1.006–1.013; P<0.001). The AAPC in the ASR during this period was 0.94%, and the trend was statistically significant (P<0.05) (Table 3, Fig. 2).

Table 3

The incidence case number of leukemia and trend in crude incidence rates and age-standardized incidence rates per million population in the Republic of Korea from 1999 to 2018.

YearsN of casesCIRASRa)ASRa)
MenWomenTotalAAPC (%)AAPC (%)IRR (per yr)
19991,1889362,1242.89b)45.0349045.458590.94b)1.009b)
20001,1059012,00642.2012742.20127
20011,2109982,20846.1181345.74454
20021,3339872,32048.2070547.29788
20031,2471,0342,28147.2174845.74993
20041,3211,0512,37248.9220346.79217
20051,3321,0152,34748.2098145.83396
20061,3421,1022,44449.9928147.05533
20071,3881,0902,47850.4372546.91184
20081,4551,1452,60052.6266348.27268
20091,5041,2122,71654.6954848.90856
20101,5721,1862,75855.2929148.55470
20111,6181,2832,90157.8909350.27748
20121,6211,2462,86756.9467048.31113
20131,7541,3173,07160.7409750.21212
20141,7851,3243,10961.2452050.30621
20151,8551,4333,28864.5316852.86386
20161,9951,4383,43367.1649554.19071
20171,9341,4543,38866.1322251.23865
20182,0371,4573,49468.1079952.44745

a)Calculated by defining the 2000 mid-year Korean population (July 1, 2000) as the standard population. b)Statistically significant trend (P< 0.05).

Abbreviations: AAPC, average annual percent change; ASR, age-standardized incidence rate; CIR, crude incidence rate; IRR, incidence rate ratio.



Figure 2. Annual incidence of leukemia in the Republic of Korea. Number of leukemia cases (A). Crude and age-standardized incidence rate of leukemia per million using the 2000 Korean standard population (B). a)Comparing to 1999 and 2018. b)Average annual percent change by Joinpoint regression analysis. c)Incidence rate ratio per year from 1999 to 2018 as calculated by Poisson regression.
Abbreviations: AAPC, average annual percent change; ASR, age-standardized incidence rate; CI, confidence interval; CIR, crude incidence rate; IRR, incidence rate ratio.

Myeloid leukemia

The number of newly diagnosed myeloid leukemia cases increased by 98.4%, from 1,222 in 1999 to 2,425 in 2018. The AAPC in incidence cases during this period was 3.81%, and the trend was statistically significant. Within a one-year increase, the IRR increased significantly to 1.038 (95% CI, 1.036–1.040; P <0.001). The CIR per million population increased by 82.4% from 25.91 in 1999 to 47.27 in 2018. Within a one-year increase, the IRR increased significantly to 1.034 (95% CI, 1.029–1.038; P <0.001). The ASR per million population increased by 29.9% from 26.21 in 1999 to 34.04 in 2018. Within a one-year increase, the IRR increased significantly to 1.014 (95% CI, 1.010–1.019; P <0.001). The AAPC in the ASR during this period was 1.44%, and the trend was statistically significant (P <0.05) (Table 4, Fig. 3).

Table 4

The incidence case number of myeloid leukemia and trend in crude incidence rates and age-standardized incidence rates per million population in the Republic of Korea from 1999 to 2018.

YearsN of casesCIRASRa)ASRa)
MenWomenTotalAAPC (%)AAPC (%)IRR (per yr)
19996965261,2223.81b)25.9099126.212181.44b)1.014b)
20006305421,17224.6559724.65597
20017206071,32727.7168327.39936
20028065881,39428.9657928.20531
20037686411,40929.1667827.92552
20048536581,51131.1640829.40229
20058126571,46930.1747828.04162
20068396771,51631.0102728.33077
20078736761,54931.5283728.48103
20089477431,69034.2073130.20098
20099807551,73534.9398630.13031
20101,0507481,79836.0466530.26675
20111,0848411,92538.4143532.02027
20121,0607871,84736.6866229.72320
20131,2388792,11741.8719132.97980
20141,2318622,09341.2306932.13509
20151,2859642,24944.1398334.03683
20161,3849142,29844.9592333.80285
20171,3459722,31745.2267832.37206
20181,4359902,42547.2701434.03950

a)Calculated by defining the 2000 mid-year Korean population (July 1, 2000) as the standard population. b)Statistically significant trend (P< 0.05).

Abbreviations: AAPC, average annual percent change; ASR, age-standardized incidence rate; CIR, crude incidence rate; IRR, incidence rate ratio.



Figure 3. Annual incidence of myeloid leukemia in the Republic of Korea. Number of myeloid leukemia cases (A). Crude and age-standardized incidence rate of myeloid leukemia per million using the 2000 Korean standard population (B). a)Comparing 1999 and 2018. b)Average annual percent change by Joinpoint regression analysis. c)Incidence rate ratio per year from 1999 to 2018 as calculated by Poisson regression.
Abbreviations: AAPC, average annual percent change; ASR, age-standardized incidence rate; CI, confidence interval; CIR, crude incidence rate; IRR, incidence rate ratio.

Multiple myeloma

The number of newly diagnosed MM cases increased by 266.5% from 469 in 1999 to 1,719 in 2018. The AAPC in incidence cases during this period was 7.33%, and the trend was statistically significant. Within a one-year increase, the IRR increased significantly to 1.071 (95% CI, 1.069–1.074; P<0.001). The CIR per million population increased by 237.1% from 9.94 in 1999 to 33.51 in 2018. Within a one-year increase, the IRR increased significantly to 1.067 (95% CI, 1.061–1.073; P<0.001). The ASR per million population increased by 71.4% from 10.22 in 1999 to 17.52 in 2018. Within a one-year increase, the IRR increased significantly to 1.030 (95% CI, 1.023–1.036; P<0.001). The AAPC in the ASR during this period was 3.05%, and the trend was statistically significant (P<0.05) (Table 5, Fig. 4).

Table 5

The incidence case number of multiple myeloma and trend in crude incidence rates and age-standardized incidence rates per million population in the Republic of Korea from 1999 to 2018.

YearsN of casesCIRASRa)ASRa)
MenWomenTotalAAPC (%)AAPC (%)IRR (per yr)
19992572124697.33b)9.9441510.224603.05b)1.030b)
200027521749210.3504610.35046
200131325156411.7801711.46171
200232823956711.7816411.07893
200333128561612.7514111.55148
200436231567713.9629912.21290
200540738779416.3095813.71200
200638638477015.7506012.94935
200745943088918.0947214.16175
200849242591718.5610114.26485
20095754621,03720.8833615.34012
20105695101,07921.6320015.12175
20116104691,07921.5319914.62146
20127065891,29525.7223517.05821
20137046461,35026.7015016.71056
20147716491,42027.9730416.87157
20157727041,47628.9686016.91477
20168457081,55330.3836817.22267
20178647791,64332.0706117.32490
20189277921,71933.5082017.51734

a)Calculated by defining the 2000 mid-year Korean population (July 1, 2000) as the standard population. b)Statistically significant trend (P< 0.05).

Abbreviations: AAPC, average annual percent change; ASR, age-standardized incidence rate; CIR, crude incidence rate; IRR, incidence rate ratio.



Figure 4. Annual incidence of multiple myeloma in the Republic of Korea. Number of multiple myeloma cases (A). Crude and age-standardized incidence rate of multiple myeloma per million using the 2000 Korean standard population (B). a)Comparing 1999 and 2018. b)Average annual percent change by Joinpoint regression analysis. c)Incidence rate ratio per year from 1999 to 2018 as calculated by Poisson regression.
Abbreviations: AAPC, average annual percent change; ASR, age-standardized incidence rate; CI, confidence interval; CIR, crude incidence rate; IRR, incidence rate ratio.

Myeloproliferative disorders

The number of newly diagnosed myeloproliferative disorders increased by 1,307.3% from 110 in 1999 to 1,548 in 2018. The AAPC in incidence cases during this period was 13.28%, and the trend was statistically significant. Within a one-year increase, the IRR increased significantly to 1.109 (95% CI, 1.105–1.112; P<0.001). The CIR per million population increased by 1,194.8% from 2.33 in 1999 to 30.17 in 2018. Within a one-year increase, the IRR increased significantly to 1.105 (95% CI, 1.097–1.112; P <0.001). The ASR per million population increased by 698.3% from 2.38 in 1999 to 19.00 in 2018. Within a one-year increase, the IRR increased significantly to 1.080 (95% CI, 1.072–1.089; P <0.001). The AAPC in the ASR during this period was 9.87%, and the trend was statistically significant (P <0.05) (Table 6, Fig. 5).

Table 6

The incidence case number of myeloproliferative disorders and trend in crude incidence rates and age-standardized incidence rates per million population in the Republic of Korea from 1999 to 2018.

YearsN of casesCIRASRa)ASRa)
MenWomenTotalAAPC (%)AAPC (%)IRR (per yr)
1999555511013.28b)2.332322.382919.87b)1.080b)
200065751402.945252.94525
200186921783.717863.64427
20021351162515.215504.96014
20032001543547.327926.76541
20041941693637.486806.68212
200528324252510.784049.50474
200628224552710.779969.23111
200736528765213.2708211.12117
200837032769714.1079811.45405
200940940281116.3321212.78754
201043140183216.6801012.76728
201150641892418.4388913.80286
201247744492118.2936613.27581
201350945696519.0866313.55994
20145954811,07621.1964714.81846
20156215111,13222.2171115.05132
20166406201,26024.6512816.13719
20177235841,30725.5120416.36598
20188097391,54830.1749219.00324

a)Calculated by defining the 2000 mid-year Korean population (July 1, 2000) as the standard population. b)Statistically significant trend (P< 0.05).

Abbreviations: AAPC, average annual percent change; ASR, age-standardized incidence rate; CIR, crude incidence rate; IRR, incidence rate ratio.



Figure 5. Annual incidence of myeloproliferative disorders in the Republic of Korea. Number of myeloproliferative disorders cases (A). Crude and age-standardized incidence rate of myeloproliferative disorders per million using the 2000 Korean standard population (B). a)Comparing 1999 and 2018. b)Average annual percent change by Joinpoint regression analysis. c)Incidence rate ratio per year from 1999 to 2018 as calculated by Poisson regression.
Abbreviations: AAPC, average annual percent change; ASR, age-standardized incidence rate; CI, confidence interval; CIR, crude incidence rate; IRR, incidence rate ratio.

Myelodysplastic syndrome

The number of newly diagnosed myelodysplastic syndromes increased by 882.0% from 139 in 1999 to 1,365 in 2018. The AAPC in incidence cases during this period was 11.49%, and the trend was statistically significant. Within a one-year increase, the IRR increased significantly to 1.099 (95% CI, 1.095–1.102; P<0.001). The CIR per million population increased by 802.0% from 2.95 in 1999 to 26.61 in 2018. Within a one-year increase, the IRR increased significantly to 1.095 (95% CI, 1.087–1.102; P<0.001). The ASR per million population increased by 410.3% from 3.00 in 1999 to 15.31 in 2018. Within a one-year increase, the IRR increased significantly to 1.064 (95% CI, 1.056–1.073; P<0.001). The AAPC in the ASR during this period was 7.59%, and the trend was statistically significant (P<0.05) (Table 7, Fig. 6).

Table 7

The incidence case number of myelodysplastic syndrome and trend in crude incidence rates and age-standardized incidence rates per million population in the Republic of Korea from 1999 to 2018.

YearsN of casesCIRASRa)ASRa)
MenWomenTotalAAPC (%)AAPC (%)IRR (per yr)
1999885113911.49b)2.947202.996307.59b)1.064b)
200090771673.513273.51327
2001129912204.595104.48965
2002165972625.444075.22327
20032341603948.155937.54460
20042531654188.621177.76107
20052801904709.654298.59289
200629919048910.002658.63391
200731425056411.479679.47229
200837726864513.0554510.52395
200944628072614.6203711.37083
201047930578415.7177811.62239
201148639087617.4810312.72050
201252131883916.6649011.46736
201354339693918.5723812.55258
201460038698619.4235412.77860
20156264071,03320.2741013.04959
20167424281,17022.8904713.84107
20177074511,15822.6036313.39331
20188285371,36526.6077315.30694

a)Calculated by defining the 2000 mid-year Korean population (July 1, 2000) as the standard population. b)Statistically significant trend (P< 0.05).

Abbreviations: AAPC, average annual percent change; ASR, age-standardized incidence rate; CIR, crude incidence rate; IRR, incidence rate ratio.



Figure 6. Annual incidence of myelodysplastic syndrome in the Republic of Korea. Number of myelodysplastic syndrome cases (A). Crude and age-standardized incidence rate of myelodysplastic syndrome per million using the 2000 Korean standard population (B). a)Comparing 1999 and 2018. b)Average annual percent change by Joinpoint regression analysis. c)Incidence rate ratio per year from 1999 to 2018 as calculated by Poisson regression.
Abbreviations: AAPC, average annual percent change; ASR, age-standardized incidence rate; CI, confidence interval; CIR, crude incidence rate; IRR, incidence rate ratio.

Malignant immunoproliferative diseases

The number of newly diagnosed malignant immunoproliferative diseases increased by 1,280.0%, from 95 in 1999 to 1,311 in 2018. The AAPC in incidence cases during this period was 14.76%, and the trend was statistically significant. Within a one-year increase, the IRR increased significantly to 1.114 (95% CI, 1.110–1.118; P<0.001). The CIR per million population increased by 1,171.6% from 2.01 in 1999 to 25.56 in 2018. Within a one-year increase, the IRR increased significantly to 1.110 (95% CI, 1.102–1.119; P<0.001). The ASR per million population increased by 751.7% from 2.05 in 1999 to 17.46 in 2018. Within a one-year increase, the IRR increased significantly to 1.090 (95% CI, 1.082–1.099; P<0.001). The AAPC in the ASR during this period was 11.82%, and the trend was statistically significant (P<0.05) (Table 8, Fig. 7).

Table 8

The incidence case number of malignant immunoproliferativediseases and trend in crude incidence rates and age-standardized incidence rates per million population in the Republic of Korea from 1999 to 2018.

YearsN of casesCIRASRa)ASRa)
MenWomenTotalAAPC (%)AAPC (%)IRR (per yr)
199945509514.76b)2.014272.0499411.82b)1.090b)
20003939781.640931.64093
20014950992.067802.00910
200298961944.031113.87658
20031651713366.955316.50023
20041751743497.198066.56316
20051982524509.243478.26204
20062122724849.900388.66932
20072272504779.708878.37596
200825132757811.699309.91273
200934838673414.7814712.09930
201031541673114.6552311.92735
201134848082816.5231612.85307
201241347188417.5587313.55260
201341250992118.2163613.44186
201443750794418.5961613.78266
201545949295118.6647313.50497
20165926031,19523.3795816.40845
20175746091,18323.0916215.98123
20186017101,31125.5551217.46422

a)Calculated by defining the 2000 mid-year Korean population (July 1, 2000) as the standard population. b)Statistically significant trend (P< 0.05).

Abbreviations: AAPC, average annual percent change; ASR, age-standardized incidence rate; CIR, crude incidence rate; IRR, incidence rate ratio.



Figure 7. Annual incidence of malignant immunoproliferative diseases in the Republic of Korea. Number of malignant immunoproliferative diseases cases (A). Crude and age-standardized incidence rate of malignant immunoproliferative diseases per million using the 2000 Korean standard population (B). a)Comparing 1999 and 2018. b)Average annual percent change by Joinpoint regression analysis. c)Incidence rate ratio per year from 1999 to 2018 as calculated by Poisson regression.
Abbreviations: AAPC, average annual percent change; ASR, age-standardized incidence rate; CI, confidence interval; CIR, crude incidence rate; IRR, incidence rate ratio.

Lymphoid leukemia

The number of newly diagnosed lymphoid leukemia cases increased by 48.5% from 550 in 1999 to 817 in 2018. The AAPC in incidence cases during this period was 2.77%, and the trend was statistically significant. Within a one-year increase, the IRR increased significantly to 1.028 (95% CI, 1.025–1.031; P<0.001). The CIR per million population increased by 36.6% from 11.66 in 1999 to 15.93 in 2018. Within a one-year increase, the IRR increased significantly to 1.024 (95% CI, 1.017–1.030; P<0.001). The ASR per million population increased by 33.7% from 11.62 in 1999 to 15.54 in 2018. Within a one-year increase, the IRR increased significantly to 1.022 (95% CI, 1.016–1.029; P<0.001). The AAPC in the ASR during this period was 2.21%, and the trend was statistically significant (P<0.05) (Table 9, Fig. 8).

Table 9

The incidence case number of lymphoid leukemia and trend in crude incidence rates and age-standardized incidence rates per million populationin the Republic of Korea from 1999 to 2018.

YearsN of casesCIRASRa)ASRa)
MenWomenTotalAAPC (%)AAPC (%)IRR (per yr)
19993162345502.77b)11.6615811.619042.21b)1.022b)
200028021649610.4346110.43461
200131622854411.3624411.42331
200233522255711.5738511.76349
200330324855111.4058911.63373
200430123253310.9930211.25614
200532822655411.3797311.87085
200633127260312.3345612.82142
200734426060412.2938312.87728
200834926060912.3267812.97963
200937328966213.3315213.75206
201036128164212.8709413.44971
201136330566813.3302813.76827
201238831270013.9039714.16193
201337131468513.5485413.57623
201443432676014.9714915.01366
201545635981515.9955316.01589
201648138386416.9037316.92706
201746336582816.1621816.11329
201846535281715.9256515.53953

a)Calculated by defining the 2000 mid-year Korean population (July 1, 2000) as the standard population. b)Statistically significant trend (P< 0.05).

Abbreviations: AAPC, average annual percent change; ASR, age-standardized incidence rate; CIR, crude incidence rate; IRR, incidence rate ratio.



Figure 8. Annual incidence of lymphoid leukemia in the Republic of Korea. Number of lymphoid leukemia cases (A). Crude and age-standardized incidence rate of lymphoid leukemia per million using the 2000 Korean standard population (B). a)Comparing 1999 and 2018. b)Average annual percent change by Joinpoint regression analysis. c)Incidence rate ratio per year from 1999 to 2018 as calculated by Poisson regression.
Abbreviations: AAPC, average annual percent change; ASR, age-standardized incidence rate; CI, confidence interval; CIR, crude incidence rate; IRR, incidence rate ratio.

Hodgkin lymphoma

The number of newly diagnosed Hodgkin lymphomas increased by 143.1% from 123 in 1999 to 299 in 2018. The AAPC in incidence cases during this period was 4.96%, and the trend was statistically significant. Within a one-year increase, the IRR increased significantly to 1.048 (95% CI, 1.042–1.053; P<0.001). The CIR per million population increased by 123.4% from 2.61 in 1999 to 5.83 in 2018. Within a one-year increase, the IRR increased significantly to 1.043 (95% CI, 1.031–1.055; P<0.001). The ASR per million population increased by 100.4% from 2.63 in 1999 to 5.27 in 2018. Within a one-year increase, the IRR increased statistically significantly to 1.039 (95% CI, 1.027–1.052; P<0.001). The AAPC in the ASR during this period was 4.04%, and the trend was statistically significant (P<0.05) (Table 10, Fig. 9).

Table 10

The incidence case number of Hodgkin lymphoma,trend in crude incidence rates, and age-standardized incidence rates per million population in the Republic of Korea from 1999 to 2018.

YearsN of casesCIRASRa)ASRa)
MenWomenTotalAAPC (%)AAPC (%)IRR (per yr)
199986371234.96b)2.607952.633354.04b)1.039b)
200090441342.819032.81903
2001100481483.091253.07055
200283621453.012942.98565
2003112461583.270653.22256
2004145592044.207464.14143
2005105531583.245483.09513
2006109681773.620593.47111
2007131742054.172573.92396
2008131882194.432784.23004
2009146742204.430414.16283
2010171772484.971954.57967
2011168982665.308175.12413
2012179902695.343105.02603
2013171932645.221634.82687
20141701112815.535515.16737
2015174982725.338394.95872
20162051103156.162825.66606
20171721172895.641155.47652
20181811182995.828365.27499

a)Calculated by defining the 2000 mid-year Korean population (July 1, 2000) as the standard population. b)Statistically significant trend (P< 0.05).

Abbreviations: AAPC, average annual percent change; ASR, age-standardized incidence rate; CIR, crude incidence rate; IRR, incidence rate ratio.



Figure 9. Annual incidence of Hodgkin lymphoma in the Republic of Korea. Number of Hodgkin lymphoma cases (A). Crude and age-standardized incidence rate of Hodgkin lymphoma per million using the 2000 Korean standard population (B). a)Comparing 1999 and 2018. b)Average annual percent change by Joinpoint regression analysis. c)Incidence rate ratio per year from 1999 to 2018 as calculated by Poisson regression.
Abbreviations: AAPC, average annual percent change; ASR, age-standardized incidence rate; CI, confidence interval; CIR, crude incidence rate; IRR, incidence rate ratio.
DISCUSSION

In the ROK, hematologic malignancies have a relatively low proportion of all cancers. None of the hematologic malignancies were among the top 10 types of cancers with the highest incidence in the ROK in 2018. Non-Hodgkin's lymphoma (5,216 cases), leukemia (3,494 cases), and multiple myeloma (1,719 cases) were ranked 11th, 14th, and 20th in the ROK in 2018, respectively [5]. The number of deaths in the ROK from non-Hodgkin lymphoma, leukemia, and multiple myeloma was 2,015, 1,911, and 961, respectively, in 2019, ranking 9th, 10th, and 16th in total cancer deaths, all in respective order [1]. Since the Annual Report of Cancer Statistics mainly describes the most common types of cancer, it is up to each researcher to analyze the statistical data of specific cancers. However, the incidence of hematologic malignancies has been increasing in the ROK. Thus, a more precise and periodic statistical analysis is needed [8]. All hematologic malignancies that were analyzed in this study showed a significant increase in the incidence. The order of increase in ASR over 20 years was as follows: malignant immunoproliferative diseases (AAPC=11.82%, IRR=1.090, P <0.05), myeloproliferative disorders (AAPC=9.87%, IRR=1.080, P <0.05), myelodysplastic syndrome (AAPC=7.59%, IRR=1.064, P <0.05), Hodgkin lymphoma (AAPC=4.04%, IRR=1.039, P <0.05), multiple myeloma (AAPC=3.05%, IRR=1.030, P <0.05), non-Hodgkin lymphoma (AAPC=2.26%, IRR=1.023, P <0.05), lymphoid leukemia (AAPC=2.21%, IRR=1.022, P <0.05), myeloid leukemia (AAPC=1.44%, IRR=1.014, P <0.05), and leukemia (AAPC=0.94%, IRR=1.009, P <0.05).

Several previous studies on hematologic malignancies in the ROK have shown similar results as obtained in this study. In the analysis from 1999 to 2008, the incidence and the ASR of all hematologic malignancies showed an increasing trend. The latter increased from 10.2% to 13.7%, and the AAPC was 3.9% [9]. Other studies from 1999 to 2012 on myeloid and lymphoid malignancies showed an increasing trend in CIR and overall ASR. The ASR for all myeloid malignancies increased from 3.31 in 1999 to 5.70 in 2012, with an AAPC of 5.4% [10]. In 2012, the ASR per 100,000 persons with Hodgkin's lymphoma, mature B-cell neoplasm, mature T/natural killer (NK)-cell neoplasm, and precursor cell neoplasm were 0.46, 6.60, 0.95, and 1.50, respectively, and increased yearly from 1999 [11]. In a recent study from 2005 to 2015, the incidence and prevalence rates of hematological malignancies increased steadily. From 2005 to 2015, the number of new patients with hematologic malignancies showed an overall gradual increase, with an increase rate of up to 56.7% over 10 years [8]. A similar trend has been observed worldwide. In an analysis of the global burden of disease data from 1990 to 2017, the number of new cases increased [12]. The ASR for all hematologic malignancies increased, except for acute lymphocytic leukemia and chronic myeloid leukemia [13]. Han et al. also demonstrated decreased ASR of acute lymphocytic leukemia and chronic myeloid leukemia, but this was not statistically significant, which is similar to the results from previous global research [8, 12, 13]. In this study, the incidence of leukemia was relatively low compared to that of other hematologic malignancies. In addition, in most hematological malignancies, the incidence was higher in males, which is also similar to the results of previous studies [8-15].

There are several possible factors contributing to the increasing trend in the incidence of hematologic malignancies. Age is the most important risk factor for cancer, and the overall incidence of cancer increases with an aging population [16]. Previous studies have also shown that the incidence of hematologic malignancies increases with age [9, 17]. However, it is difficult to explain how the incidence of hematologic malignancies increases because of the aging population alone. In addition to the increase in CIR, ASR also tends to increase significantly. In addition to the aging population, the following possibilities can be considered as possible causes for the increase in hematologic malignancies. First, there is a possibility of a detection bias. Improved access to healthcare facilities and the use of new screening and diagnostic technologies may be another cause [18, 19]. Exposure to diagnostic or therapeutic ionizing radiation, such as X-rays, computed tomography (CT), gamma rays, radiopharmaceuticals, and charged particles can also increase the risk of hematologic malignancies [20, 21]. One study found that the risk of radiation-induced malignancies from CT radiation may increase as CT-based screening becomes more widely used at the population level [22]. The increased exposure to extremely low-frequency electric and magnetic fields (ELF-EMFs) may be another cause [23, 24]. Over the last half century, the use of chemicals has continuously increased, and new chemicals have been developed. The possibility that such exposure to diverse chemical pollution in the workplace or residence may have been a cause of hematologic malignancies cannot be ruled out [25, 26]. Efforts are needed to determine new environmental cancer risk factors in the future.

This study had the following limitations. First, this study used the 61 sets of cancer incidence data provided by the KOSIS. Therefore, hematologic malignancies cannot be analyzed in greater detail. In the future, it will be necessary to analyze hematologic malignancies in a more subdivided manner. Clinically important diseases such as acute myeloid leukemia, acute lymphoid leukemia, chronic myeloid leukemia, chronic lymphoid leukemia, T-cell lymphoma, and B-cell lymphoma require additional detailed analysis. Second, the analysis results of this study may be slightly different from the annual report of cancer statistics. This is due to differences in statistical analysis methods, statistics package programs, and/or standard population settings (Segi’s world standard population or Korean standard population) used, along with differences in the handling of decimal places. It would be better to interpret the current state of occurrence based on trends rather than detailed numbers.

An aging society is when the proportion of the population aged ≥65 years comprises 7% of the total population, an ‘aged society’ when it is over 14%, and a ‘post-aged society’ when it is over 20%. The ROK entered an aging society in 2000, an aged society in 2018, and is expected to enter a post-aged society by 2025. In 2050, the proportion of the population aged ≥65 years is expected to be 39.8% [27]. It is highly likely that the incidence of hematologic malignancies will continue to increase with the aging population. In addition to social and medical preparations for the possibility of this increase, more research should be conducted in the future. More well-designed studies are needed to elucidate the causes of this increase.

ACKNOWLEDGMENTS

The authors thank all the Gwangju Jeonnam Regional Cancer Center members at Chonnam National University Hwasun Hospital. The authors also thank the Regional Cancer Registries in Korea and the Korea Central Cancer Registry. We thank the researchers for their efforts in collecting and managing data in each region.

Authors’ Disclosures of Potential Conflicts of Interest

No potential conflicts of interest relevant to this article were reported.

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