Date 2013/June/21
Type of manuscript: original article
Manuscript title: No association between depression and risk of hepatocellular carcinoma in older people in Taiwan
Running head：depression and hepatocellular carcinoma Authors' full names:
Shih-Wei Lai1,2, Cheng-Li Lin3,4, Kuan-Fu Liao5,6, Wen-Chi Chen5,7
1School of Medicine, China Medical University and 2Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan
3 Department of Public Health, China Medical University and 4Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
5Graduate Institute of Integrated Medicine, China Medical University and 6Department of Internal Medicine, Taichung Tzu Chi General Hospital 7Department of Urology, China Medical University Hospital, Taichung,
Taiwan
Corresponding author: Kuan-Fu Liao, Department of Internal Medicine,
Taichung Tzu Chi General Hospital, No.66, Sec. 1, Fongsing Road, Tanzi District, Taichung City, 427, Taiwan
Phone: 886-4-2205-2121 Fax: 886-4-2203-3986
Abstract
Objectives. The objective of this study was to determine whether there is a
relationship between depression and risk of hepatocellular carcinoma (HCC) in older people in Taiwan. Methods. A case-control study was conducted to analyze the database from the Taiwan National Health Insurance program. We selected 1815 subjects aged 65 years or older with newly diagnosed HCC as the case group and 7260 subjects without HCC as the comparison group, from 2000 to 2010. Both groups were compared to measure the risk of HCC. Results. After controlling for confounders, the odds of HCC was 0.81 in subjects with depression (95%
confidence interval = 0.59, 1.11), as compared with non-depression subjects.
Conclusions. We conclude that no association is detected between depression and
risk of hepatocellular carcinoma in older people in Taiwan. Key words: depression; hepatocellular carcinoma; older people
Introduction
Until now, controversies exist regarding the relationship between depression and subsequent cancer risk. That is, some studies showed an increased risk, but others showed no increased risk. Similarly, no specific evidence is available about the relationship between depression and risk of hepatocellular carcinoma (HCC) in older people. In order to explore this issue, a population-based case-control study was conducted to analyze the database from the Taiwan National Health Insurance program.
Methods
The details of the Taiwan National Health Insurance program can be documented in previous studies.5-7 In this case-control study, we randomly selected 1815 subjects aged 65 years or older with newly diagnosed HCC as the case group (1132 men and 683 women, mean age 74.31 years and standard deviation 6.29 years) (according to International Classification of Diseases 9th Revision-Clinical Modification, ICD-9 codes 155, 155.0 and 155.2) and 7260 subjects without HCC as the comparison group (4528 men and 2732 women, mean age 74.09 years and standard deviation 6.53 years). Both groups were matched with sex, age and index year of diagnosing HCC, from 2000 to 2010. The index date was defined as the date of diagnosing HCC. In order to reduce the confounding effects, subjects with any cancer (ICD-9 codes 140–
208), major psychiatric diseases (ICD-9 codes 291–293, 294.0, 294.8–294.9, 295, 296.0–296.1, 296.4–296.9, and 297–298), other dementia (290.0–290.4, and 294.1) or mental retardation (ICD-9 codes 317–319) diagnosed before the index date were excluded. Depression (ICD-9 codes 331.0) and other co-morbidities potentially associated with HCC were diagnosed before the index date.7
Results
We compared the basic characteristics and co-morbidities between the HCC group and the comparison group. Table 1 shows that the HCC group was more likely to have diabetes mellitus, cirrhosis, other chronic hepatitis, hepatitis B infection, hepatitis C infection and alcoholism, with statistical significance. There were 114 subjects with depression among the HCC group (6.28%) and 385 subjects with depression among the comparison group (5.30%), without significant difference (P = 0.10). After controlling for confounding factors, multivariable logistic regression analysis demonstrated that the odds ratio (OR) of HCC was 0.81 in subjects with depression (95% confidence interval (CI) = 0.59, 1.11), as compared with non-depression subjects (Table 2).
Discussion
To date, there is no consensus about the association between depression and subsequent cancer risk.1-4 One cohort study by Chen et al in Taiwan showed that
cancer (95% CI = 1.03, 3.14), but HCC not mentioned specifically.2 In this present study, despite we controlled for co-morbidities potentially associated with HCC, no association is detected between depression and HCC risk in older people (OR = 0.81, 95% CI = 0.59, 1.11). General speaking, 70-90% of all HCC cases are significantly associated cirrhosis or other chronic liver diseases worldwide.8 Depression is a mood disorder, not causing chronic inflammation of liver. Therefore, these two diseases should have their unique pathogenesis without potential linking. Since formal depression diagnostic procedures were not recorded in this database, more prospective studies are necessary to validate our findings.
Funding
This study was supported in part by Taiwan Department of Health Clinical Trial and
Research Center of Excellence (DOH 102-TD-B-111-004) and China Medical University Hospital (Grant number 1MS1).The funding agency did not influence the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Specific author contributions
Shih-Wei Lai: (1) substantial contributions to the conception of this article; (2) conducted the study and interpreted the data; (3) initiated the draft of the article and critically revised the article.
Cheng-Li Lin: (1) conducted the statistical analysis and critically revised the article. Kuan-Fu Liao and Wen-Chi Chen: (1) conducted the study and critically revised the article.
Acknowledgements
The authors thank the National Health Research Institute in Taiwan for providing the
insurance claims data.
Conflict of Interest Statement
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Table 1. Characteristics between hepatocellular carcinoma group and comparison group Hepatocellular carcinoma No N=7260 Yes N=1815 n (%) n (%) P value
Age group (year)
65-74 4260 58.68 1065 58.68 0.99
75-84 3000 41.32 750 41.32
Sex
Men 4528 62.37 1132 62.37 0.99
Women 2732 37.63 683 37.63
Comorbidities before index date*
Depression 385 5.30 114 6.28 0.10
Diabetes mellitus 1941 26.74 636 35.04 <0.0001
Cirrhosis 137 1.89 990 54.56 <0.0001
Other chronic hepatitis 1163 16.02 1033 56.91 <0.0001
Hepatitis B infection 112 1.54 361 19.89 <0.0001
Hepatitis C infection 135 1.86 600 33.06 <0.0001
Alcoholism 57 0.79 24 1.32 0.03
Data are presented as the number of subjects in each group, with percentages given in parentheses. Chi-square test comparing subjects with and without hepatocellular carcinoma
*Co-morbidities included before index date were as follows: depression (ICD-9 codes 296.2– 296.3,
300.4, and 311), diabetes mellitus (ICD-9 codes 250), cirrhosis (ICD-9 codes 571.2, and 571.5– 571.6),
other chronic hepatitis (ICD-9 codes 571.40– 571.41, 571.49, and 571.8– 571.9), hepatitis B infection (ICD-9 codes V02.61, 070.20, 070.22, 070.30 , and 070.32), hepatitis C infection (ICD-9 codes V02.62, 070.41, 070.44, 070.51 , and 070.54), and alcoholism (ICD-9 codes 303, 305.00, 305.01, 305.02, 305.03, and V11.3)
Table 2. Odds ratio and 95% confidence interval of hepatocellular carcinoma associated with depression and other comorbidities
Crude Adjusted †
Variable OR (95%CI) OR (95%CI)
Age (per one year) 1.01 (1.00, 1.01) 1.04 (1.03, 1.05)
Comorbidities before index date (yes vs. no)
Depression 1.20 (0.97, 1.49) 0.81 (0.59, 1.11)
Diabetes mellitus 1.48 (1.33, 1.65) 1.04 (0.89, 1.22)
Cirrhosis 62.39 (51.46, 75.65) 28.55 (23.17, 35.19)
Other chronic hepatitis 6.93 (6.19, 7.75) 2.23 (1.89, 2.63)
Hepatitis B infection 15.84 (12.72, 19.73) 5.87 (4.40, 7.84)
Hepatitis C infection 26.06 (21.42, 31.72) 7.72 (6.00, 9.93)
Alcoholism 1.70 (1.05, 2.74) 0.85 (0.43, 1.68)
†Adjusted for age, diabetes mellitus, cirrhosis, other chronic hepatitis, hepatitis B infection, hepatitis C infection, and alcoholism
