2011;20:473-475. Published OnlineFirst February 4, 2011.
Cancer Epidemiol Biomarkers Prev
Ji-An Liang, Li-Min Sun, Chih-Hsin Muo, et al.
Taiwan
The Analysis of Depression and Subsequent Cancer Risk in
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10.1158/1055-9965.EPI-10-1280
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Research Article
The Analysis of Depression and Subsequent Cancer
Risk in Taiwan
Ji-An Liang1,2, Li-Min Sun3, Chih-Hsin Muo4,5, Fung-Chang Sung4,5, Shih-Ni Chang4,6,7, and Chia-Hung Kao2,8
Abstract
Background:Patients with depression are suggestive of having a tendency toward a marginally significant association with the subsequent cancer risk. The aim of this study was to evaluate the possible relationship between depression and cancer risk in Taiwan.
Methods:We used the data of the National Health Insurance system of Taiwan to assess this issue. The Cox proportional hazard regression analysis was conducted to estimate the effects of depression on the cancer risk. Results:In patients with depression, there was no significant change in the risk of developing overall cancer or for the site-specific cancer and all showed the same direction (positive) except for colorectal cancer, which had a negative direction.
Conclusions: This population-based study did not find Taiwanese patients with depression to have a higher risk to develop overall cancer or site-specific cancer.
Impact:Depression does not increase cancer risk.Cancer Epidemiol Biomarkers Prev; 20(3); 473–5. 2011 AACR.
Introduction
Depression accounts for almost 12% of all total years lived with disability worldwide in 2000 (1) and is more common among Taiwanese than previously suggested (2). It has been proposed as a predisposing factor in the development of cancer, and 2 meta-analyses suggested a tendency toward a small and marginally significant asso-ciation between depression and subsequent cancer risk (3, 4). To the best of our knowledge, there are no popula-tion-based studies which outline the possible relationship between depression and cancer in Taiwan. The aim of this
study was to investigate the risk of cancer among patients with depression in Taiwan.
Methods
This study used data retrieved from The National Health Research Institute, containing all reimbursement claims records from 1996 to 2008 for 1 million randomly selected insurants (5).
In this study, we identified newly diagnosed depres-sion patients in the period of 2000–2002 as the exposure group (ICD-9-CM 296.2–296.9). The index date for the depression patients was the date of their first medical visit. Subjects with the history of malignant cancer [International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) 140-208] diagnosed before index date or with missing information on age or sex were excluded. For the comparison group, we used a systematic random sampling method and selected 8 insured people without depression in the same period, with frequency matched with the depression group on age and sex.
Person-years of follow-up time were calculated for each person until cancer diagnosed or censored. We also considered hypertension (ICD-9-CM 401-405), diabetes mellitus (ICD-9-CM 250), hyperlipidemia (ICD-9-CM 272), and heart disease (ICD-9-CM 410-429) before the index date as baseline comorbidities.
We assessed the incidence density and rate ratio (RR) of cancer by each variable, using Poisson regression. The Cox proportion hazard regression analysis was used to estimate HR and 95% CI. All data measurements were Authors' Affiliations:1
Department of Radiation Oncology, China Medical University Hospital; 2
School of Medicine, College of Medicine, China Medical University, Taichung;3
Department of Radiation Oncology, Zuoy-ing Armed Forces General Hospital, Kaohsiung;4Management Office for Health Data, China Medical University Hospital;5Institute of Environmental Health, College of Public Health, and6The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University, Taichung;7 Insti-tute of Biomedical Sciences, Academia Sinica, Taipei; and8
Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan
Note: J-A. Liang and L-M. Sun contributed equally to this work. Corresponding Authors: Chia-Hung Kao, Department of Nuclear Med-icine and PET Center, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 404, Taiwan. Phone: 22052121-7412; Fax: 886-4-22336174. E-mail: d10040@mail.cmuh.org.tw; or Shih-Ni Chang, Manage-ment Office for Health Data, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 404, Taiwan. Phone: 886-4-22052121-7805; Fax: 886-4-22339216. E-mail: u9665856@cmu.edu.tw
doi: 10.1158/1055-9965.EPI-10-1280
2011 American Association for Cancer Research.
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done by SAS statistical software (version 9.1 for Win-dows; SAS Institute Inc.), and the significance level was set to be 0.05.
Results
The incidence of cancer was slightly higher in the depression group than in the nondepression group (5.50 vs. 5.42 per 1,000 person-years; Table 1). The inci-dence densities of cancer were higher in men and increased with age. The RR of cancer was higher in younger group than in the nondepression group (30–39 years of age, 3.30 vs. 1.84 per 1,000 person-years, RR¼ 1.80, 95% CI¼ 1.27–2.54).
The risk of cancer was not significant between the depression group and the nondepression group (adjusted HR ¼ 1.03, 95% CI ¼ 0.91–1.15; Table 2). Besides, the specific analyses on cancer type also did not observe any significant relationship between depression and cancer including hematologic malignancy, colorectal cancer,
lung cancer, breast cancer, uterus, cervical, ovary, and vaginal cancer, prostate cancer, and brain cancer.
Discussion
The results did not show any significant relationship between the depression and cancer risk; however, the RR had the direction toward positive association for overall cancer and site-specific cancer except for the colorectal cancer.
One large study with long follow-up time conducted in Baltimore area showed that major depression was asso-ciated with a higher hazard for overall cancer, as well as for breast cancer and prostate cancer, and the authors suggested the association between depression and hor-monally medicated cancers (6). Another nationwide cohort study from Denmark found that the standardized incidence ratio was 1.05 (95% CI ¼ 1.03–1.07) and con-cluded that most of the excess risk could be attributed to an increased risk of tobacco-related cancers (7).
Table 1. Comparisons of incidence density of cancer between depression group and nondepression group by characteristics
Variables Depression
No Yes
n Case Person-years Ratea
n Case Person-years Ratea RR 95% CI
All 67,352 2,571 474,401 5.42 8,419 321 58,341 5.50 1.02 (0.90–1.14) Sex Women 40,728 1,336 290,062 4.61 5,091 163 36,000 4.53 0.98 (0.84–1.16) Men 26,624 1,235 184,339 6.70 3,328 158 22,342 7.07 1.06 (0.89–1.25) Age, y <30 16,096 71 115,210 0.62 2,012 8 14,486 0.55 0.90 (0.43–1.86) 30–39 13,048 174 94,690 1.84 1,631 39 11,808 3.30 1.80 (1.27–2.54) 40–49 12,896 394 94,568 4.17 1,612 43 11,602 3.71 0.89 (0.65–1.22) 50–64 13,344 753 95,972 7.85 1,668 92 11,722 7.85 1.00 (0.81–1.24) 65 11,968 1,179 73,960 15.9 1,496 139 8,723 15.9 1.00 (0.84–1.19) Occupation White collar 34,978 1,071 249,095 4.30 4,075 119 28,979 4.11 0.96 (0.79–1.15) Blue collar 22,802 1,101 159,640 6.90 2,673 121 18,417 6.57 0.95 (0.79–1.15) Others 9,572 399 65,666 6.08 1,671 81 10,945 7.40 1.22 (0.96–1.55) Urbanization level 1 20,272 690 143,772 4.80 2,583 88 18,151 4.85 1.01 (0.81–1.26) 2 19,252 731 136,461 5.36 2,631 95 18,262 5.20 0.97 (0.78–1.20) 3 12,103 429 84,959 5.05 1,352 54 9,309 5.80 1.15 (0.87–1.52) 4 15,720 721 109,170 6.60 1,853 84 12,619 6.66 1.01 (0.80–1.26) Comorbidity Hypertension 13,743 1,028 90,298 11.4 2,422 170 15,681 10.8 0.95 (0.81–1.12) Diabetes mellitus 4,710 361 30,214 12.0 898 68 5,520 12.3 1.03 (0.80–1.34) Hyperlipidemia 7,006 478 48,429 9.87 1,386 79 9,376 8.43 0.85 (0.67–1.08) Heart disease 10,276 754 66,916 11.3 2,445 147 15,964 9.2 0.82 (0.68–0.98) aPer 1,000 person-year. Liang et al.
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Multivariate model (Table 2) analyses for our study showed no significant increment of the overall cancer risk for patients with depression. For the site-specific cancer analysis, we still could not find any significant relation-ship between depression and any cancer risk. All the directions were toward positive relationship except for the colorectal cancer. Our data showed that the HR for colorectal cancer was 0.77 (95% CI¼ 0.55–1.10). It may be comparable with The Danish cohort study, which detected a marginally significantly lower risk for reactive depression, and the possibility of decreased motivation for surveillance among patients with depressed mood should be considered (7). Positive relationship between depression and breast cancer may exist (6, 8), but most researches did not show this association (3). Although showing the tendency of positive relationship, our data did not support any significant finding for breast caner either. We specified brain tumor to see whether there is an increased risk among patients with depression similar to the findings of the Danish cohort study. Unfortunately, 1.44 HR did not accompany with a significant higher risk. In conclusion, this population-based retrospective cohort study failed to prove any significant association
between depression and subsequent overall or any site-specific cancer risk in Taiwan. Although meta-analyses suggested a tendency toward a marginally significant association, our data provide little, if any, support in the positive direction for most cancers.
Disclosure of Potential Conflicts of Interest No potential conflicts of interest were disclosed. Grant Support
This study was supported by the National Sciences Council, Execu-tive Yuan (grant numbers DOH 97-HP-1101, 2008–2010), China Medical University Hospital (grant number 1MS1, DMR-94-080), Taiwan Department of Health Clinical Trial and Research Center and for Excellence (grant number DOH 100-TD-B-111-004), and Taiwan Department of Health Cancer Research Center for Excellence (DOH100-TD-C-111-005).
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received December 8, 2010; revised January 13, 2011; accepted January 14, 2011; published OnlineFirst February 4, 2011.
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Table 2. HRs and 95% CIs of cancer associated with depression in Cox's regression analysis in different cancer
Variable Case Multivariate model,aHR (95% CI)
All cancers 2,892 1.03 (0.91–1.15)
Hematologic malignancyb 130 1.10 (0.64–1.87)
Colorectal cancer 408 0.77 (0.55–1.10)
Lung cancer 363 1.01 (0.65–1.58)
Breast cancer (women only) 325 1.09 (0.78–1.53)
Uterus, cervical, ovary, and vaginal cancer (women only) 208 1.16 (0.84–1.60)
Prostate cancer (men only) 123 1.33 (0.79–2.23)
Brain cancer 35 1.44 (0.55–3.76)
a
Adjusted for age, sex, urbanization, and comorbidity. bICD-9-CM: hematologic malignancy, 200.xx
–203.xx and 205.xx–208.xx; colorectal cancer, 153.xx and 154.xx; lung cancer, 162.xx; breast cancer, 174.xx and 175.xx; uterus, cervical, ovary, and vaginal cancer, 179.xx–184.xx; prostate cancer, 185.xx; brain cancer, 179.xx and 180.xx–184.xx.
Depression and Cancer Risk in Taiwan
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