|Year : 2016 | Volume
| Issue : 2 | Page : 721-724
Systemic lupus erythematous increased lung cancer risk: Evidence from a meta-analysis
Yusheng Wu1, Qian Hou2
1 Department of Internal Medicine, Hospital of Shandong University, Jinan 250012, China
2 Department of Internal Medicine, Chinese PLA 148th Hospital, Zibo 255300, Shandong, China
|Date of Web Publication||25-Jul-2016|
No. 44, Wenhuaxi Road, Jinan 250012, Shandong
Source of Support: None, Conflict of Interest: None
Aims: Several studies suggested that systemic lupus erythematosus (SLE) were associated with the risk of lung cancer. However, other studies did not confirm the result. Therefore, we conducted a meta-analysis to investigate this association.
Materials and Methods: A systematic literature search was conducted using the PubMed, Cochrane Library, EMBASE, Chinese National Knowledge Infrastructure, and WANFANG databases for relevant published articles. The strength of the associations between SLE and lung cancer risk was measured by odds ratio (ORs) and 95% confidence interval (CIs).
Results: All 12 studies, involving a total of 57,890 SLE patients were included in the meta-analysis. A statistically significant association between SLE and lung cancer risk was found. The data showed that SLE patients had an increased lung cancer risk (OR = 1.60; 95% CI: 1.44–1.77; P < 0.00001). In the subgroup analysis of study design, population and hospital based studies also showed an increased lung cancer risks (OR = 1.68; 95% CI: 1.49–1.89; P < 0.00001; OR = 1.38; 95% CI: 1.12–1.69; P = 0.002). In the subgroup analysis of follow-up duration, significant results were observed in the study with more than 10 years (OR = 1.72; 95% CI: 1.08–2.73; P = 0.02) and < 10 years (OR = 1.59; 95% CI: 1.43–1.77; P < 0.00001), respectively. In addition, studies with large and small sample size also showed an increased lung cancer risk (OR = 1.58; 95% CI: 1.42–1.76; P < 0.00001; OR = 1.76; 95% CI: 1.16–2.67; P = 0.007).
Conclusion: This meta-analysis suggested that SLE was associated with an increased lung cancer risk.
Keywords: Association, lung cancer, meta-analysis, systemic lupus erythematous
|How to cite this article:|
Wu Y, Hou Q. Systemic lupus erythematous increased lung cancer risk: Evidence from a meta-analysis. J Can Res Ther 2016;12:721-4
| > Introduction|| |
Lung cancer remains the deadliest cancer worldwide despite improvements in diagnostic and therapeutic techniques. Its incidence has yet to peak in many parts of the world, particularly in China, which has become a major public health challenges. The mechanism of lung carcinogenesis is not fully understood. Systemic lupus erythematosus (SLE) is an autoimmune disease that has multifaceted effects on its sufferers. SLE has an estimated incidence of 5/100,000 persons and a prevalence of 100/100,000 persons in the United States. A relapsing-remitting condition in which periods of mild disease activity alternate with flares of increased disease activity; SLE is manifested mainly in women, also in children and men, with clinical and pathologic manifestations involving almost all bodily organs. Several studies suggested that SLE were associated with the risk of lung cancer. However, other studies did not confirm the result.,,,,,,,,,,, Therefore, in order to derive a more comprehensive estimation of the association between SLE and lung cancer risk, we conducted a meta-analysis to investigate this association.
| > Materials and Methods|| |
A systematic literature search was conducted using the PubMed, Cochrane Library, EMBASE, Chinese National Knowledge Infrastructure, and WANFANG databases for relevant published articles (the last search update was May 18, 2015). Search terms “lung cancer,” “lung tumor,” “systemic lupus erythematosus,” and “SLE” were used individually and in various pairwise combinations. All eligible studies were retrieved, and their bibliographies were checked for other relevant publications.
Inclusion and exclusion criteria
All selected studies complied with the following two criteria: (1) Case-control or cohort study on the association between SLE and lung cancer risk; (2) sufficient published data for estimating the odds ratio (OR) with 95% confidence interval (CI). Studies were excluded if one of the following exists: (1) Not relevant to SLE or lung cancer, (2) animal studies, (3) editorials, reviews and abstracts, and (4) overlapping of studies.
The following information was extracted from each study: The first author's name; the year of publication; study design; race; age; the percent of male patients; follow-up years; the number of patients; and covariants.
The included studies were assessed independently by the two reviewers using the Newcastle–Ottawa Scale (NOS). The NOS employs a star rating system to assess the quality from three broad perspectives of the study: (1) Selection of the study groups, (2) comparability of the groups, and (3) identification of the exposure (for case-control studies) or outcome of interest (for cohort studies). Scores ranged from 0 to 9 stars.
The strength of the association between SLE and lung cancer risk was measured by ORs and 95% CIs. Between study heterogeneity was assessed by Chi-square test, and was quantified using the I2 statistic (ranged from 0% to 100%), which was defined as the percentage of the observed between-study variability that is due to heterogeneity rather than chance. A random-effects model (DerSimonian–Laird method) was used. To access the stability of the meta-analysis, a one-way sensitivity analysis was carried out. Publication bias was assessed by visual inspection of funnel plots, in which the standard error of log (OR) of each study was plotted against its log (OR). The Egger's test was used to assess publication bias statistically. All statistical tests were performed by using RevMan version 5.1 software (Nordic Cochrane Center, Copenhagen, Denmark) and Stata version 11.0 software (Stata Corporation, College Station, TX, USA). A P < 0.05 was considered significant. All the P values were two-sided.
| > Results|| |
The characteristics of the selected studies are listed in [Table 1]. All 12 studies, involving a total of 57,890 SLE patients were included in the meta-analysis. The publication years of all the selected studies ranged from 1996 to 2013 years. All of the included patients were Caucasians.
Quantitative data synthesis
As shown in [Figure 1], a statistically significant association between SLE and lung cancer risk was found. The data showed that SLE patients had an increased lung cancer risk (OR = 1.60; 95% CI: 1.44–1.77; P < 0.00001). In the subgroup analysis of study design, population and hospital based studies also showed an increased lung cancer risk (OR = 1.68; 95% CI: 1.49–1.89; P < 0.00001; OR = 1.38; 95% CI: 1.12–1.69; P = 0.002). In the subgroup analysis of follow-up duration, significant results were observed in study with more than 10 years (OR = 1.72; 95% CI: 1.08–2.73; P = 0.02) and <10 years (OR = 1.59; 95% CI: 1.43–1.77; P < 0.00001), respectively. In addition, studies with large and small sample size also showed an increased lung cancer risk (OR = 1.58; 95% CI: 1.42–1.76; P < 0.00001; OR = 1.76; 95% CI: 1.16–2.67; P = 0.007). All the results are shown in [Table 2].
In the sensitivity analysis, the pooled OR did not qualitatively change by omitting a single study at a time [Figure 2]. Publication bias was evaluated with both visual assessment of funnel plots and Egger's test in the meta-analysis. As illustrated in [Figure 3], symmetrical funnel plots indicated that there was no evidence of publication bias for the meta-analysis, and the results of Begg's test also led to the same conclusion (P = 0.622).
|Figure 2: Sensitivity analysis on the association between SLE and lung cancer|
Click here to view
|Figure 3: Funnel plot of publication bias on the association between SLE and lung cancer|
Click here to view
| > Discussion|| |
Some published studies have been reported inconclusive results about the association between SLE and lung cancer risk, probably due to limited predictive ability with relatively small sample size. A meta-analysis is a statistical method, which can overcome the problem of small sample size and inadequate statistical power in different studies. For this reason, a meta-analysis was performed to obtain a comprehensive conclusion on the basis of pooled data from all 12 eligible studies.
In the present meta-analysis, we found a significant association between SLE and lung cancer risk in the overall population. In the subgroup analysis by study design, follow-up duration, and sample size, the results indicated that SLE was significantly associated with the lung cancer risk.
Smoking has been confirmed, as an important etiologic agent for lung cancers in SLE (as in the general population). A recent case-cohort study in SLE found the lung cancer risk of lupus patients who smoked (compared to those who did not) to be increased almost four-fold (adjusted HR - 3.6, 95% CI: 1.32, 9.83). This underlines once again the universal importance of smoking cessation, particularly in chronic autoimmune disorders such as SLE.
Our study had some advantages. First, the methodological issues for meta-analysis, such as, one-way sensitivity analysis were well investigated. Second, this meta-analysis included almost all the studies, thus the statistical power was enough. Third, funnel plots and Egger's tests did not find potential publication bias. Finally, no heterogeneity was found in this meta-analysis. However, this meta-analysis had some limitations. First, subgroup analyzes were not performed on the factors such as alcohol and smoking because insufficient data could be extracted from the primary articles. Second, in view of small negative studies are less likely to published, the possibility of publication bias cannot be ruled out completely, even though the Egger's test and funnel plots did not provide any evidence of publication bias in this meta-analysis. Third, a lack of original data from the eligible studies limited evaluation of the effects of SLE in lung cancer risk in Asians.
| > Conclusion|| |
This meta-analysis suggested that SLE was associated with increased lung cancer risk.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Marshall HM, Bowman RV, Yang IA, Fong KM, Berg CD. Screening for lung cancer with low-dose computed tomography: A review of current status. J Thorac Dis 2013;5:S524-39.
Zhou C. Lung cancer molecular epidemiology in China: Recent trends. Transl Lung Cancer Res 2014;3:270-9.
Naleway AL, Davis ME, Greenlee RT, Wilson DA, McCarty DJ. Epidemiology of systemic lupus erythematosus in rural Wisconsin. Lupus 2005;14:862-6.
Lau CS, Mak A. The socioeconomic burden of SLE. Nat Rev Rheumatol 2009;5:400-4.
Abu-Shakra M, Gladman DD, Urowitz MB. Malignancy in systemic lupus erythematosus. Arthritis Rheum 1996;39:1050-4.
Mellemkjaer L, Andersen V, Linet MS, Gridley G, Hoover R, Olsen JH. Non-Hodgkin's lymphoma and other cancers among a cohort of patients with systemic lupus erythematosus. Arthritis Rheum 1997;40:761-8.
Ramsey-Goldman R, Mattai SA, Schilling E, Chiu YL, Alo CJ, Howe HL, et al.
Increased risk of malignancy in patients with systemic lupus erythematosus. J Investig Med 1998;46:217-22.
Sultan SM, Ioannou Y, Isenberg DA. Is there an association of malignancy with systemic lupus erythematosus? An analysis of 276 patients under long-term review. Rheumatology (Oxford) 2000;39:1147-52.
Cibere J, Sibley J, Haga M. Systemic lupus erythematosus and the risk of malignancy. Lupus 2001;10:394-400.
Nived O, Bengtsson A, Jönsen A, Sturfelt G, Olsson H. Malignancies during follow-up in an epidemiologically defined systemic lupus erythematosus inception cohort in southern Sweden. Lupus 2001;10:500-4.
Björnådal L, Löfström B, Yin L, Lundberg IE, Ekbom A. Increased cancer incidence in a Swedish cohort of patients with systemic lupus erythematosus. Scand J Rheumatol 2002;31:66-71.
Ragnarsson O, Gröndal G, Steinsson K. Risk of malignancy in an unselected cohort of Icelandic patients with systemic lupus erythematosus. Lupus 2003;12:687-91.
Tarr T, Gyorfy B, Szekanecz E, Bhattoa HP, Zeher M, Szegedi G, et al.
Occurrence of malignancies in Hungarian patients with systemic lupus erythematosus: Results from a single center. Ann N
Y Acad Sci 2007;1108:76-82.
Parikh-Patel A, White RH, Allen M, Cress R. Cancer risk in a cohort of patients with systemic lupus erythematosus (SLE) in California. Cancer Causes Control 2008;19:887-94.
Dreyer L, Faurschou M, Mogensen M, Jacobsen S. High incidence of potentially virus-induced malignancies in systemic lupus erythematosus: A long-term follow-up study in a Danish cohort. Arthritis Rheum 2011;63:3032-7.
Bernatsky S, Ramsey-Goldman R, Labrecque J, Joseph L, Boivin JF, Petri M, et al.
Cancer risk in systemic lupus: An updated international multi-centre cohort study. J Autoimmun 2013;42:130-5.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]