Rheumatol Int DOI 10.1007/s00296-014-2982-6
Original Article
No overall increased risk of cancer in patients with rheumatoid arthritis: a nationwide dynamic cohort study in Taiwan Wen‑Kuan Huang · Meng‑Jiun Chiou · Chang‑Fu Kuo · Yung‑Chang Lin · Kuang‑Hui Yu · Lai‑Chu See
Received: 22 December 2013 / Accepted: 3 March 2014 © Springer-Verlag Berlin Heidelberg 2014
Abstract The association between rheumatoid arthritis (RA) and cancer is still controversial. This study aimed to estimate cancer incidence (both overall and site-specific) among patients with RA and to determine whether their cancer risk was higher than in the general population. We used the nationwide dynamic cohort from the National Health Insurance Research Database of Taiwan and obtained a total of 30,504 patients with no history of cancer who were newly diagnosed with RA between 1996 and 2008; they were followed up until 2010. Standardized incidence ratios (SIR) by age for various types of cancer were calculated in 5-year calendar periods by 5-year age intervals (quinquinquennium) to compare elevated risk of increasing age and increased cancer rate in later calendar years in Taiwan. During 225,432 person-years of follow-up, 1,595 cancers occurred, corresponding to 7.08 per 1,000 person-years. The SIR for all cancers was 0.93 (95 % CI 0.88–0.97). Most cancers were found in the first 2 years after diagnosis of RA, W.-K. Huang · Y.-C. Lin Division of Hematology‑Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan M.-J. Chiou · L.-C. See (*) Department of Public Health, College of Medicine, Chang Gung University, 259 Wen‑Hwa 1st Road, Kweisan, Taoyuan 333, Taiwan e-mail: [email protected]; [email protected] C.-F. Kuo · K.-H. Yu Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan L.-C. See Biostatistics Core Laboratory, Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
but the incidence decreased afterward. A significant excess of Hodgkin’s lymphoma (SIR 3.31, 95 % CI 1.24–8.81) and non-Hodgkin’s lymphoma (SIR 3.18, 95 % CI 2.64–3.83) was seen among patients with RA, whereas the risk of colorectal cancer was 29 % lower than the general population. In conclusion, this study showed that patients with RA do not have increased overall risk of cancers but have higher risk of hematologic malignancies and lower risk of colorectal cancer, than the general population. Keywords Rheumatoid arthritis · Cancer · Cohort study · Standardized incidence ratio
Introduction The risk of cancer in patients with rheumatoid arthritis (RA) has been investigated extensively in several populationbased studies. For all cancers, some studies have shown an increased risk in patients with RA [1–4], whereas other studies found similar [5–9], or less [10, 11] overall cancer risk among patients with RA than the general population. A review by Chakravarty et al. [12] did not find increased incidence of cancer in patients with RA. A meta-analysis of observational studies by Smitten et al. [13] demonstrated an overall 5 % increased risk of cancer. Among site-specific malignancies, most studies consistently indicated that patients with RA have a higher risk for developing hematopoietic malignancy [1, 3, 5, 6, 8, 14–17] and lower risk of colorectal cancer [2, 5–7, 9, 17]. The inflammatory process that results in immunologic imbalance has been suggested as an important factor in lymphoma development [18]. Non-steroid anti-inflammation drugs (NSAID) may play a role in decreased colon cancer among patients with RA, though the mechanism is unclear [19].
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In the few studies conducted in Asian populations to examine the association between cancer and RA [20– 22], overall cancer incidence in patients with RA was not significantly higher than the general population in two reports [21, 22]. Yamada et al. [20] enrolled 7,566 patients with RA from 2001 to 2005 and found 173 patients diagnosed with cancer during 25,567 personyears (6.77 per 1,000 person-years). The standardized incidence ratio (SIR) was 1.18 (95 % confidence internal, 1.02–1.37). In this study, we used a nationwide dynamic cohort in Taiwan who were with newly diagnosed RA between 1996 and 2008, and followed them until 2010. Unlike a fixed cohort, the advantages of a dynamic cohort (patients were recruited at different times) are that the numbers of participants do not decline over time and do not suffer from the aging problem over time [23]. This study aimed to: (a) estimate both crude and age-specific incidences of cancers (all and site-specific) among patients with RA; and (b) investigate whether patients with RA were at higher risk for all and site-specific cancers than the general population.
Rheumatol Int
Study population Patients with RA was identified with the International Classification of Diseases, Clinical Modification (ICD-9-CM) of 714.0 and verified with the Registry of Catastrophic Illness Database. In Taiwan, patients with RA are eligible for a catastrophic illness certificate after being reviewed by two specialists based on clinical presentations, laboratory studies, imaging studies, and fulfilling the diagnostic criteria of the 1987 American College of Rheumatology classification [24]. An advantage of holding a catastrophic illness certificate is exemption from co-payment for medical treatment for the catastrophic illness, namely RA here. Patients younger than 18 years of age were excluded (n = 930). Patients with primary or metastatic cancers before diagnosis of RA were also excluded (n = 654). As other autoimmune rheumatic diseases are reportedly associated with cancer, we also excluded patients with systemic lupus erythematosus (ICD-9-CM 710.0), Sjögren’s syndrome (ICD-9-CM 710.2), systemic sclerosis (ICD-9-CM 710.1), dermatomyositis (ICD-9-CM 710.4) and polymyositis (ICD-9-CM 710.3) (n = 969). Identification of cancer cases
Materials and methods Data sources Taiwan began the National Health Insurance (NHI) program in 1995 to provide compulsory universal health insurance for citizens in Taiwan. Currently, 98 % of the population are covered in the Taiwan NHI program. The bureau of NHI cooperates with the National Health Research Institute to manage and maintain all the insurance claim data as National Health Insurance Research Databases (NHIRDs). The databases comprise comprehensive information including date of birth, gender, diagnostic codes, surgery or procedures received, medications prescribed, admission date, hospitalization, discharge date, and medical institutions codes and expenditure amounts. Approval from institutional review board of Chang Gung Medical Foundation was obtained (101–4763B). The identification number of each patient had already been encrypted for privacy protection; therefore, informed consent was not needed and was waived. Study design The nationwide dynamic cohort study was used. Patients who were newly diagnosed with RA from January 1, 1996 to December 31, 2008 in Taiwan were identified and were followed up until either the date of diagnosis of cancer, date of death, or December 31, 2010; whichever came first.
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Cases of newly diagnosed cancer were identified using code ICD-9-CM (140–208.91) and verified using catastrophic illnesses database. In Taiwan, registration of cancer as a catastrophic illness is approved after evaluating pathology and/or cytology evidence and a comprehensive review for exemption from all copayments. Statistical analysis Crude incidence rates of cancers were calculated as the total number of cancers during the follow-up time divided by person-years at risk. Person-years at risk was defined as the sum of patients from the diagnosis of RA to the diagnosis of first cancer, dropout from the NHI program, death or December 31, 2010; whichever came first. For age-specific rates, as an individual patient aged, he or she contributed data to successive 5-year age groups over the follow-up period. The total number of personyears was the amount of observation time contributed by each individual according to given 5-year age categories, summed up for all individuals. These person-years formed the denominators of the rates by various 5-year age categories [25]. The numerators of the rates by 5-year age categories were the number of cancers based on the age diagnosed with the cancer, not the age of RA diagnosis. SIRs were computed as ratios of observed numbers of cancers in this study to the expected number of cancers on the basis of the age–time-specific incidence rates in
Rheumatol Int
5-year age intervals from the general Taiwanese population (1996–2000, 2001–2005, 2006–2010) from Taiwan National Cancer Registry [25]. This quinquinquennium method (5-year age intervals × 5-year calendar cancer rate) could synchronize with the national cancer incidence rates which were typically published by 5-year age intervals every 5-year calendar years [26]. The standard mortality ratio (SMR) was also computed as the ratio of observed deaths for patients with RA in this study to expected deaths, based on the age–time-specific mortality rate for the general Taiwanese population. The death status in patients with RA was based on Registry of Catastrophic Illness Database. The mortality rate for the general population was based on Ministry of Health and Welfare (1996–2010) [27]. Confidence intervals of SIRs and SMRs were based on the Poisson distribution of observed cancer cases [28].
Risk of hematological cancers in patients with RA Among 1,595 patients with all cancers, 144 (9.0 %) were hematologic cancers. Patients with RA had a significantly higher risk of hematologic malignancies than the general population (SIR 2.27, 95 % CI 1.93–2.67). Significantly, higher risks of hematologic cancer in patients with RA than the general population were consistently seen for both genders, three age groups and all follow-up periods. The highest risk was in the first year (SIR 3.68) and declined gradually about half (SIR 1.92) after 8-year follow-up (Table 2). Among 144 cases of hematologic cancers, 111 (77.1 %) were non-Hodgkin’s lymphoma (NHL), 29 (20.1 %) were leukemia, and 4 (2.8 %) were Hodgkin’s lymphoma. Patients with RA had higher risk of Hodgkin’s lymphoma than the general population (SIR 3.31, 95 % CI 1.24–8.81), followed by NHL (SIR 3.18, 95 % CI 2.64–3.83) and leukemia (SIR 1.06, 95 % CI 0.74–1.53; Table 2).
Results
Risk of site‑specific solid cancers in patients with RA
Incidence of all cancers in patients with RA
Patients with RA did not have a higher site-specific rate of solid cancer than the general population. In fact, they had significantly lower risk of colorectal cancer than the general population did (SIR 0.71, 95 % CI 0.61–0.82; Table 3).
This dynamic cohort consisted of 30,504 patients with RA. Three times as many women (n = 23,680) were included as men (n = 6,824). Median age at the time of RA diagnosis for this cohort was 53.6 years. In the average follow-up of 7.4 years, contributing a total of 225,432 person-years, 1,595 patients had cancers after being diagnosed with RA, corresponding to 7.08 per 1,000 person-years (95 % CI 6.73–7.42). Figure 1a (males) and b (females) display age-specific incidence rate of all cancers for patients with RA and the Taiwan general population for three 5-calendar-year periods. Males had a higher incidence rate of all cancers than females did, among both general population and patients with RA. The all-cancer incidence rates rose as age increased, but dropped after age 80 for both male and female patients with RA. The rates were highest for the general population over the years 2006–2010, followed by 2001–2005, and 1996–2000. The incidence rate of all cancers for patients with RA during the study period was lower than for the general population (SIR 0.93, 95 % CI 0.88–0.97). The lower SIR for all cancers was mainly due to the elderly group (SIR 0.83, 95 % CI 0.78–0.89). When stratified by follow-up time since RA diagnosis, risk of all cancers was highest for the first year of follow-up (SIR 1.31, 95 % CI 1.16– 1.49) and decreased thereafter. Younger groups (18–39, 40–64 years old) had significantly higher SIRs in the first year after RA diagnosis, but patients older than 65 years had significantly lower SIR after 4 years of follow-up (Table 1).
Discussion To our best knowledge, this is the largest study to estimate risk of cancer among patients with RA in an Asian population. We found patients with RA had lower risk for developing all cancers than the general population did (SIR 0.93, 95 % CI 0.88–0.97); and this lower SIR was mainly due to the elderly group (SIR 0.83, 95 % CI 0.78–0.89). They had increased risk of hematologic malignancies, and reduced risk of colorectal cancer, than the general population, consistent with previous studies [1, 3–5, 7, 9]. Whether overall cancer incidence for patients with RA is higher than for the general population is unsettled. Several studies have shown overall cancer risk does not increase in the RA population [11, 12], but several studies of more than 20,000 patients with RA found overall cancer risk to be just slightly higher (1–8 %) [1, 3, 5, 7]. Ethnicity may also influence the estimation of cancer risk [29]. A contemporary study in Korea found risk of malignancy did not significantly differ from the general population [21], whereas an excess risk of 18 % in incidence of all malignancies among RA patients was reported in Japan [20]. In our study, we cautiously calculated SIR using the quinquinquennium method and shifting age over time during the follow-up period. The SIR of all cancers for patients with RA was 0.93 (95 % CI 0.88–0.97), which was attributed to
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Rheumatol Int
Fig. 1 a Incidence rate (the number of new cancer cases per 100,000 person-year) of all cancers for male patients with rheumatoid arthritis (RA) and men in the general Taiwanese population (1996–2010). b Incidence rate (the number of new cancer cases per 100,000 person-year) of all cancers for female patients with RA and for women in the general Taiwanese population (1996–2010)
lower incidence of all cancers in patients aged 65 years or older. The SMR was 1.03 (95 % CI 1.0–1.08) in this age group (≥65 years), which suggests that the higher death rate of older patients with RA obscures the cancer incidence, especially after a long follow-up period. In this study, SIRs were significantly higher than one for the first year and became insignificant after 2 years of follow-up. These findings agree with previous studies that assessed change in SIRs stratified by time since the start of follow-up [1, 5, 7]. Why cancer risk was higher
13
for patients with RA for the first year after RA diagnosis is unclear. Increased frequency of surveillance and health checkup for younger patients with RA (18–39 and 40– 64 years old) may be a reason, but requires further investigation. Chen’s 1996–2005 cohort study of patients with RA excluded those aged
Original Article
No overall increased risk of cancer in patients with rheumatoid arthritis: a nationwide dynamic cohort study in Taiwan Wen‑Kuan Huang · Meng‑Jiun Chiou · Chang‑Fu Kuo · Yung‑Chang Lin · Kuang‑Hui Yu · Lai‑Chu See
Received: 22 December 2013 / Accepted: 3 March 2014 © Springer-Verlag Berlin Heidelberg 2014
Abstract The association between rheumatoid arthritis (RA) and cancer is still controversial. This study aimed to estimate cancer incidence (both overall and site-specific) among patients with RA and to determine whether their cancer risk was higher than in the general population. We used the nationwide dynamic cohort from the National Health Insurance Research Database of Taiwan and obtained a total of 30,504 patients with no history of cancer who were newly diagnosed with RA between 1996 and 2008; they were followed up until 2010. Standardized incidence ratios (SIR) by age for various types of cancer were calculated in 5-year calendar periods by 5-year age intervals (quinquinquennium) to compare elevated risk of increasing age and increased cancer rate in later calendar years in Taiwan. During 225,432 person-years of follow-up, 1,595 cancers occurred, corresponding to 7.08 per 1,000 person-years. The SIR for all cancers was 0.93 (95 % CI 0.88–0.97). Most cancers were found in the first 2 years after diagnosis of RA, W.-K. Huang · Y.-C. Lin Division of Hematology‑Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan M.-J. Chiou · L.-C. See (*) Department of Public Health, College of Medicine, Chang Gung University, 259 Wen‑Hwa 1st Road, Kweisan, Taoyuan 333, Taiwan e-mail: [email protected]; [email protected] C.-F. Kuo · K.-H. Yu Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan L.-C. See Biostatistics Core Laboratory, Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
but the incidence decreased afterward. A significant excess of Hodgkin’s lymphoma (SIR 3.31, 95 % CI 1.24–8.81) and non-Hodgkin’s lymphoma (SIR 3.18, 95 % CI 2.64–3.83) was seen among patients with RA, whereas the risk of colorectal cancer was 29 % lower than the general population. In conclusion, this study showed that patients with RA do not have increased overall risk of cancers but have higher risk of hematologic malignancies and lower risk of colorectal cancer, than the general population. Keywords Rheumatoid arthritis · Cancer · Cohort study · Standardized incidence ratio
Introduction The risk of cancer in patients with rheumatoid arthritis (RA) has been investigated extensively in several populationbased studies. For all cancers, some studies have shown an increased risk in patients with RA [1–4], whereas other studies found similar [5–9], or less [10, 11] overall cancer risk among patients with RA than the general population. A review by Chakravarty et al. [12] did not find increased incidence of cancer in patients with RA. A meta-analysis of observational studies by Smitten et al. [13] demonstrated an overall 5 % increased risk of cancer. Among site-specific malignancies, most studies consistently indicated that patients with RA have a higher risk for developing hematopoietic malignancy [1, 3, 5, 6, 8, 14–17] and lower risk of colorectal cancer [2, 5–7, 9, 17]. The inflammatory process that results in immunologic imbalance has been suggested as an important factor in lymphoma development [18]. Non-steroid anti-inflammation drugs (NSAID) may play a role in decreased colon cancer among patients with RA, though the mechanism is unclear [19].
13
In the few studies conducted in Asian populations to examine the association between cancer and RA [20– 22], overall cancer incidence in patients with RA was not significantly higher than the general population in two reports [21, 22]. Yamada et al. [20] enrolled 7,566 patients with RA from 2001 to 2005 and found 173 patients diagnosed with cancer during 25,567 personyears (6.77 per 1,000 person-years). The standardized incidence ratio (SIR) was 1.18 (95 % confidence internal, 1.02–1.37). In this study, we used a nationwide dynamic cohort in Taiwan who were with newly diagnosed RA between 1996 and 2008, and followed them until 2010. Unlike a fixed cohort, the advantages of a dynamic cohort (patients were recruited at different times) are that the numbers of participants do not decline over time and do not suffer from the aging problem over time [23]. This study aimed to: (a) estimate both crude and age-specific incidences of cancers (all and site-specific) among patients with RA; and (b) investigate whether patients with RA were at higher risk for all and site-specific cancers than the general population.
Rheumatol Int
Study population Patients with RA was identified with the International Classification of Diseases, Clinical Modification (ICD-9-CM) of 714.0 and verified with the Registry of Catastrophic Illness Database. In Taiwan, patients with RA are eligible for a catastrophic illness certificate after being reviewed by two specialists based on clinical presentations, laboratory studies, imaging studies, and fulfilling the diagnostic criteria of the 1987 American College of Rheumatology classification [24]. An advantage of holding a catastrophic illness certificate is exemption from co-payment for medical treatment for the catastrophic illness, namely RA here. Patients younger than 18 years of age were excluded (n = 930). Patients with primary or metastatic cancers before diagnosis of RA were also excluded (n = 654). As other autoimmune rheumatic diseases are reportedly associated with cancer, we also excluded patients with systemic lupus erythematosus (ICD-9-CM 710.0), Sjögren’s syndrome (ICD-9-CM 710.2), systemic sclerosis (ICD-9-CM 710.1), dermatomyositis (ICD-9-CM 710.4) and polymyositis (ICD-9-CM 710.3) (n = 969). Identification of cancer cases
Materials and methods Data sources Taiwan began the National Health Insurance (NHI) program in 1995 to provide compulsory universal health insurance for citizens in Taiwan. Currently, 98 % of the population are covered in the Taiwan NHI program. The bureau of NHI cooperates with the National Health Research Institute to manage and maintain all the insurance claim data as National Health Insurance Research Databases (NHIRDs). The databases comprise comprehensive information including date of birth, gender, diagnostic codes, surgery or procedures received, medications prescribed, admission date, hospitalization, discharge date, and medical institutions codes and expenditure amounts. Approval from institutional review board of Chang Gung Medical Foundation was obtained (101–4763B). The identification number of each patient had already been encrypted for privacy protection; therefore, informed consent was not needed and was waived. Study design The nationwide dynamic cohort study was used. Patients who were newly diagnosed with RA from January 1, 1996 to December 31, 2008 in Taiwan were identified and were followed up until either the date of diagnosis of cancer, date of death, or December 31, 2010; whichever came first.
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Cases of newly diagnosed cancer were identified using code ICD-9-CM (140–208.91) and verified using catastrophic illnesses database. In Taiwan, registration of cancer as a catastrophic illness is approved after evaluating pathology and/or cytology evidence and a comprehensive review for exemption from all copayments. Statistical analysis Crude incidence rates of cancers were calculated as the total number of cancers during the follow-up time divided by person-years at risk. Person-years at risk was defined as the sum of patients from the diagnosis of RA to the diagnosis of first cancer, dropout from the NHI program, death or December 31, 2010; whichever came first. For age-specific rates, as an individual patient aged, he or she contributed data to successive 5-year age groups over the follow-up period. The total number of personyears was the amount of observation time contributed by each individual according to given 5-year age categories, summed up for all individuals. These person-years formed the denominators of the rates by various 5-year age categories [25]. The numerators of the rates by 5-year age categories were the number of cancers based on the age diagnosed with the cancer, not the age of RA diagnosis. SIRs were computed as ratios of observed numbers of cancers in this study to the expected number of cancers on the basis of the age–time-specific incidence rates in
Rheumatol Int
5-year age intervals from the general Taiwanese population (1996–2000, 2001–2005, 2006–2010) from Taiwan National Cancer Registry [25]. This quinquinquennium method (5-year age intervals × 5-year calendar cancer rate) could synchronize with the national cancer incidence rates which were typically published by 5-year age intervals every 5-year calendar years [26]. The standard mortality ratio (SMR) was also computed as the ratio of observed deaths for patients with RA in this study to expected deaths, based on the age–time-specific mortality rate for the general Taiwanese population. The death status in patients with RA was based on Registry of Catastrophic Illness Database. The mortality rate for the general population was based on Ministry of Health and Welfare (1996–2010) [27]. Confidence intervals of SIRs and SMRs were based on the Poisson distribution of observed cancer cases [28].
Risk of hematological cancers in patients with RA Among 1,595 patients with all cancers, 144 (9.0 %) were hematologic cancers. Patients with RA had a significantly higher risk of hematologic malignancies than the general population (SIR 2.27, 95 % CI 1.93–2.67). Significantly, higher risks of hematologic cancer in patients with RA than the general population were consistently seen for both genders, three age groups and all follow-up periods. The highest risk was in the first year (SIR 3.68) and declined gradually about half (SIR 1.92) after 8-year follow-up (Table 2). Among 144 cases of hematologic cancers, 111 (77.1 %) were non-Hodgkin’s lymphoma (NHL), 29 (20.1 %) were leukemia, and 4 (2.8 %) were Hodgkin’s lymphoma. Patients with RA had higher risk of Hodgkin’s lymphoma than the general population (SIR 3.31, 95 % CI 1.24–8.81), followed by NHL (SIR 3.18, 95 % CI 2.64–3.83) and leukemia (SIR 1.06, 95 % CI 0.74–1.53; Table 2).
Results
Risk of site‑specific solid cancers in patients with RA
Incidence of all cancers in patients with RA
Patients with RA did not have a higher site-specific rate of solid cancer than the general population. In fact, they had significantly lower risk of colorectal cancer than the general population did (SIR 0.71, 95 % CI 0.61–0.82; Table 3).
This dynamic cohort consisted of 30,504 patients with RA. Three times as many women (n = 23,680) were included as men (n = 6,824). Median age at the time of RA diagnosis for this cohort was 53.6 years. In the average follow-up of 7.4 years, contributing a total of 225,432 person-years, 1,595 patients had cancers after being diagnosed with RA, corresponding to 7.08 per 1,000 person-years (95 % CI 6.73–7.42). Figure 1a (males) and b (females) display age-specific incidence rate of all cancers for patients with RA and the Taiwan general population for three 5-calendar-year periods. Males had a higher incidence rate of all cancers than females did, among both general population and patients with RA. The all-cancer incidence rates rose as age increased, but dropped after age 80 for both male and female patients with RA. The rates were highest for the general population over the years 2006–2010, followed by 2001–2005, and 1996–2000. The incidence rate of all cancers for patients with RA during the study period was lower than for the general population (SIR 0.93, 95 % CI 0.88–0.97). The lower SIR for all cancers was mainly due to the elderly group (SIR 0.83, 95 % CI 0.78–0.89). When stratified by follow-up time since RA diagnosis, risk of all cancers was highest for the first year of follow-up (SIR 1.31, 95 % CI 1.16– 1.49) and decreased thereafter. Younger groups (18–39, 40–64 years old) had significantly higher SIRs in the first year after RA diagnosis, but patients older than 65 years had significantly lower SIR after 4 years of follow-up (Table 1).
Discussion To our best knowledge, this is the largest study to estimate risk of cancer among patients with RA in an Asian population. We found patients with RA had lower risk for developing all cancers than the general population did (SIR 0.93, 95 % CI 0.88–0.97); and this lower SIR was mainly due to the elderly group (SIR 0.83, 95 % CI 0.78–0.89). They had increased risk of hematologic malignancies, and reduced risk of colorectal cancer, than the general population, consistent with previous studies [1, 3–5, 7, 9]. Whether overall cancer incidence for patients with RA is higher than for the general population is unsettled. Several studies have shown overall cancer risk does not increase in the RA population [11, 12], but several studies of more than 20,000 patients with RA found overall cancer risk to be just slightly higher (1–8 %) [1, 3, 5, 7]. Ethnicity may also influence the estimation of cancer risk [29]. A contemporary study in Korea found risk of malignancy did not significantly differ from the general population [21], whereas an excess risk of 18 % in incidence of all malignancies among RA patients was reported in Japan [20]. In our study, we cautiously calculated SIR using the quinquinquennium method and shifting age over time during the follow-up period. The SIR of all cancers for patients with RA was 0.93 (95 % CI 0.88–0.97), which was attributed to
13
Rheumatol Int
Fig. 1 a Incidence rate (the number of new cancer cases per 100,000 person-year) of all cancers for male patients with rheumatoid arthritis (RA) and men in the general Taiwanese population (1996–2010). b Incidence rate (the number of new cancer cases per 100,000 person-year) of all cancers for female patients with RA and for women in the general Taiwanese population (1996–2010)
lower incidence of all cancers in patients aged 65 years or older. The SMR was 1.03 (95 % CI 1.0–1.08) in this age group (≥65 years), which suggests that the higher death rate of older patients with RA obscures the cancer incidence, especially after a long follow-up period. In this study, SIRs were significantly higher than one for the first year and became insignificant after 2 years of follow-up. These findings agree with previous studies that assessed change in SIRs stratified by time since the start of follow-up [1, 5, 7]. Why cancer risk was higher
13
for patients with RA for the first year after RA diagnosis is unclear. Increased frequency of surveillance and health checkup for younger patients with RA (18–39 and 40– 64 years old) may be a reason, but requires further investigation. Chen’s 1996–2005 cohort study of patients with RA excluded those aged
