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Systemic lupus erythematous and malignancy risk: a meta-analysis.

Cao L, Tong H, Xu G, Liu P, Meng H, Wang J, Zhao X, Tang Y, Jin J - PLoS ONE (2015)

Bottom Line: However, the results have been inconclusive.A random or fixed effects model was chosen to calculate the pooled RR according to heterogeneity test.Although an increased risk of MM, and esophageal, bladder and non-melanoma skin cancers was identified from the accumulated data in these studies, this observation requires confirmation.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, the First Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China; Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.

ABSTRACT

Background: Pilot studies have estimated cancer incidence in patients with systemic lupus erythematous (SLE). However, the results have been inconclusive. To ascertain the correlation between SLE and malignancy more comprehensively and precisely, we conducted a meta-analysis.

Methods: PubMed, the Cochrane Library and Embase databases through June 2014, were searched to identify observational studies evaluating the association between SLE and malignancy. The outcomes from these studies were measured as relative risks (RRs). A random or fixed effects model was chosen to calculate the pooled RR according to heterogeneity test. Between-study heterogeneity was assessed by estimating I2 index. Publication bias was assessed by Egger's test.

Results: A total of 16 papers, including 59,662 SLE patients, were suitable for the meta-analysis. Of these papers, 15 reported RRs for overall malignancy, 12 for non-Hodgkin lymphoma (NHL) and lung cancer, 7 for bladder cancer, 6 for Hodgkin lymphoma (HL) and leukemia, 5 for skin melanoma, and liver and thyroid cancers, 4 for multiple myeloma (MM), and esophageal and vaginal/vulvar cancers and 3 for laryngeal and non-melanoma skin cancers. The pooled RRs were 1.28 (95% CI, 1.17-1.41) for overall cancer, 5.40 (95% CI, 3.75-7.77) for NHL, 3.26(95% CI, 2.17-4.88) for HL, 2.01(95% CI, 1.61-2.52) for leukemia, 1.45(95% CI, 1.04-2.03) for MM, 4.19(95% CI, 1.98-8.87) for laryngeal cancer, 1.59 (95% CI, 1.44-1.76) for lung cancer, 1.86(95% CI, 1.21-2.88) for esophageal cancer, 3.21(95% CI, 1.70-6.05) for liver cancer, 3.67(95% CI, 2.80-4.81) for vaginal/vulvar cancer, 2.11(95% CI, 1.12-3.99) for bladder cancer, 1.51(95% CI, 1.12-2.03) for non-melanoma skin cancer, 1.78(95% CI, 1.35-2.33) for thyroid cancer, and 0.65(95% CI, 0.50-0.85) for skin melanoma. Only the meta-analyses of overall malignancy, NHL, and liver and bladder cancers produced substantial heterogeneity (I2, 57.6% vs 74.3% vs 67.7% vs 82.3%). No apparent publication bias was detected except for NHL studies.

Conclusions: Our data support an association between SLE and malignancy, not only demonstrating an increased risk for NHL, HL, leukemia, and some non-hematologic malignancies, including laryngeal, lung, liver, vaginal/vulvar, and thyroid malignancies, but also a reduced risk for skin melanoma. Although an increased risk of MM, and esophageal, bladder and non-melanoma skin cancers was identified from the accumulated data in these studies, this observation requires confirmation.

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Galbraith plots of association between SLE and NHL.
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pone.0122964.g006: Galbraith plots of association between SLE and NHL.

Mentions: As shown in Fig 5, twelve studies, involving 58,098 SLE patients, demonstrated an increased incidence of NHL with the exception of one study [20]. Of them, one study [9] revealed a dramatically elevated RR (44.40; 95% CI, 11.90–111.00). The pooled RR of all studies was 5.40 (95% CI, 3.75–7.77), but with substantial heterogeneity (Ι2 = 74.3%). The possible source of heterogeneity might be attributed to two studies [9,21], one performed in Finland and the other in the USA, according to the Galbraith plot (Fig 6). The regional subgroup analysis confirmed the European studies produced considerable heterogeneity (Ι2 = 78.5%) while the North American studies didn’t (Table 3). The pooled RRs for two areas were 6.74 (95% CI, 2.98–15.25) and 7.86 (95% CI, 4.52–13.70), respectively (S1 Fig). One Asian study reported a RR of 15.37 with wide 95% CI (2.90–37.68). One international multicenter study [24] with 16,409 lupus patients presented a RR of 4.39 (95% CI, 3.46–5.49). The results of the other subgroup analyses were shown in Table 3. A higher risk was observed in the hospital-based subgroup than in the population-based one (pooled RR, 7.94 vs 5.06; S2 Fig). Considerable heterogeneity was present in the hospital-based cohorts (Ι2 = 84.5%). The heterogeneity among the population-based studies (Ι2 = 4.4%) might not be important. In the analysis stratified by diagnostic criteria for SLE, the risk of NHL (pooled RR and 95% CI) was significantly decreased in the subgroup with ACR criteria, 4.97 (3.94–6.27), compared to that with ARA criteria (S3 Fig). The heterogeneity in the subgroup with ACR criteria might not be important (Ι2 = 2.3%). When NHLs in the first year of SLE were excluded, the summary risk estimate was 3.92(95% CI, 2.97–5.18) with moderate heterogeneity (Ι2 = 34.4%), otherwise, it increased (8.15, 95% CI, 3.63–18.32) with considerable heterogeneity (Ι2 = 81.0%; S4 Fig). Only one study [12] demonstrated that females had a lower risk to develop NHL than males (RR, 4.1 vs. 9.4). The same study estimated RRs by different age groups (12.8 for 0–39 y; 8.1 for 40–59 y; 3.7 for >60 y) and length of follow-up (2.21 for <1 y; 1.26 for 1–4 y; 1.16 for 5–9 y; 1.12 for 10–19 y; 1.43 for >20 y). Egger’s test showed that Publication bias was potentially present in the meta-analysis of NHL (P = 0.035; Fig 7). Sensitivity analysis confirmed that the risk estimate for NHL was stable and reliable.


Systemic lupus erythematous and malignancy risk: a meta-analysis.

Cao L, Tong H, Xu G, Liu P, Meng H, Wang J, Zhao X, Tang Y, Jin J - PLoS ONE (2015)

Galbraith plots of association between SLE and NHL.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401738&req=5

pone.0122964.g006: Galbraith plots of association between SLE and NHL.
Mentions: As shown in Fig 5, twelve studies, involving 58,098 SLE patients, demonstrated an increased incidence of NHL with the exception of one study [20]. Of them, one study [9] revealed a dramatically elevated RR (44.40; 95% CI, 11.90–111.00). The pooled RR of all studies was 5.40 (95% CI, 3.75–7.77), but with substantial heterogeneity (Ι2 = 74.3%). The possible source of heterogeneity might be attributed to two studies [9,21], one performed in Finland and the other in the USA, according to the Galbraith plot (Fig 6). The regional subgroup analysis confirmed the European studies produced considerable heterogeneity (Ι2 = 78.5%) while the North American studies didn’t (Table 3). The pooled RRs for two areas were 6.74 (95% CI, 2.98–15.25) and 7.86 (95% CI, 4.52–13.70), respectively (S1 Fig). One Asian study reported a RR of 15.37 with wide 95% CI (2.90–37.68). One international multicenter study [24] with 16,409 lupus patients presented a RR of 4.39 (95% CI, 3.46–5.49). The results of the other subgroup analyses were shown in Table 3. A higher risk was observed in the hospital-based subgroup than in the population-based one (pooled RR, 7.94 vs 5.06; S2 Fig). Considerable heterogeneity was present in the hospital-based cohorts (Ι2 = 84.5%). The heterogeneity among the population-based studies (Ι2 = 4.4%) might not be important. In the analysis stratified by diagnostic criteria for SLE, the risk of NHL (pooled RR and 95% CI) was significantly decreased in the subgroup with ACR criteria, 4.97 (3.94–6.27), compared to that with ARA criteria (S3 Fig). The heterogeneity in the subgroup with ACR criteria might not be important (Ι2 = 2.3%). When NHLs in the first year of SLE were excluded, the summary risk estimate was 3.92(95% CI, 2.97–5.18) with moderate heterogeneity (Ι2 = 34.4%), otherwise, it increased (8.15, 95% CI, 3.63–18.32) with considerable heterogeneity (Ι2 = 81.0%; S4 Fig). Only one study [12] demonstrated that females had a lower risk to develop NHL than males (RR, 4.1 vs. 9.4). The same study estimated RRs by different age groups (12.8 for 0–39 y; 8.1 for 40–59 y; 3.7 for >60 y) and length of follow-up (2.21 for <1 y; 1.26 for 1–4 y; 1.16 for 5–9 y; 1.12 for 10–19 y; 1.43 for >20 y). Egger’s test showed that Publication bias was potentially present in the meta-analysis of NHL (P = 0.035; Fig 7). Sensitivity analysis confirmed that the risk estimate for NHL was stable and reliable.

Bottom Line: However, the results have been inconclusive.A random or fixed effects model was chosen to calculate the pooled RR according to heterogeneity test.Although an increased risk of MM, and esophageal, bladder and non-melanoma skin cancers was identified from the accumulated data in these studies, this observation requires confirmation.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, the First Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China; Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.

ABSTRACT

Background: Pilot studies have estimated cancer incidence in patients with systemic lupus erythematous (SLE). However, the results have been inconclusive. To ascertain the correlation between SLE and malignancy more comprehensively and precisely, we conducted a meta-analysis.

Methods: PubMed, the Cochrane Library and Embase databases through June 2014, were searched to identify observational studies evaluating the association between SLE and malignancy. The outcomes from these studies were measured as relative risks (RRs). A random or fixed effects model was chosen to calculate the pooled RR according to heterogeneity test. Between-study heterogeneity was assessed by estimating I2 index. Publication bias was assessed by Egger's test.

Results: A total of 16 papers, including 59,662 SLE patients, were suitable for the meta-analysis. Of these papers, 15 reported RRs for overall malignancy, 12 for non-Hodgkin lymphoma (NHL) and lung cancer, 7 for bladder cancer, 6 for Hodgkin lymphoma (HL) and leukemia, 5 for skin melanoma, and liver and thyroid cancers, 4 for multiple myeloma (MM), and esophageal and vaginal/vulvar cancers and 3 for laryngeal and non-melanoma skin cancers. The pooled RRs were 1.28 (95% CI, 1.17-1.41) for overall cancer, 5.40 (95% CI, 3.75-7.77) for NHL, 3.26(95% CI, 2.17-4.88) for HL, 2.01(95% CI, 1.61-2.52) for leukemia, 1.45(95% CI, 1.04-2.03) for MM, 4.19(95% CI, 1.98-8.87) for laryngeal cancer, 1.59 (95% CI, 1.44-1.76) for lung cancer, 1.86(95% CI, 1.21-2.88) for esophageal cancer, 3.21(95% CI, 1.70-6.05) for liver cancer, 3.67(95% CI, 2.80-4.81) for vaginal/vulvar cancer, 2.11(95% CI, 1.12-3.99) for bladder cancer, 1.51(95% CI, 1.12-2.03) for non-melanoma skin cancer, 1.78(95% CI, 1.35-2.33) for thyroid cancer, and 0.65(95% CI, 0.50-0.85) for skin melanoma. Only the meta-analyses of overall malignancy, NHL, and liver and bladder cancers produced substantial heterogeneity (I2, 57.6% vs 74.3% vs 67.7% vs 82.3%). No apparent publication bias was detected except for NHL studies.

Conclusions: Our data support an association between SLE and malignancy, not only demonstrating an increased risk for NHL, HL, leukemia, and some non-hematologic malignancies, including laryngeal, lung, liver, vaginal/vulvar, and thyroid malignancies, but also a reduced risk for skin melanoma. Although an increased risk of MM, and esophageal, bladder and non-melanoma skin cancers was identified from the accumulated data in these studies, this observation requires confirmation.

Show MeSH
Related in: MedlinePlus