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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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Relative risk of overall malignancy in patients with SLE compared with the general population.(N, number of patients with SLE; n, number of cancer cases).
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pone.0122964.g002: Relative risk of overall malignancy in patients with SLE compared with the general population.(N, number of patients with SLE; n, number of cancer cases).

Mentions: Of all included studies, fifteen, involving 58,077 patients with SLE, estimated RRs for overall malignancy. As shown in Fig 2, RR of each study ranged from 0.89–2.60 and the pooled RR by random effects analysis was 1.28 (95% CI, 1.17–1.41), with substantial heterogeneity (Ι2 = 57.6%). The Galbraith plot showed that three studies might be the major source of the heterogeneity (Fig 3), two conducted in Europe [9,23] and one in North America [13]. The regional subgroup analysis suggested that the European studies, as well as North American ones produced substantial heterogeneity (Ι2, 61.3% vs. 65.6%; Table 2). The pooled RRs in two areas were equally 1.37 (Table 2 and S1 Fig). We also performed subgroup analyses by study type, diagnostic criteria for SLE, whether cancers diagnosed in the first year of SLE being excluded, gender, and SLE duration (Table 2). As shown in S2 Fig, a higher risk of overall cancer was noted in the hospital-based cohorts (pooled RR, 1.33; 95% CI, 1.14–1.55) compared with the population-based ones (pooled RR, 1.29; 95% CI, 1.09–1.53). Considerable heterogeneity was found in the hospital-based subgroup (Ι2 = 75.8%), moderate heterogeneity in the population-based one (Ι2 = 45.4%). The studies adopting the American College of Rheumatology criteria for the classification of SLE (ACR, 1982)[32] conferred a lower risk to develop a cancer (pooled RR, 1.40; 95% CI, 1.19–1.65) than the study with 1971 criteria of American Rheumatism Association (ARA, 1971)[33] did (RR, 2.6; 95% CI, 1.5–4.4; S3 Fig). The cohorts with ACR criteria produced substantial heterogeneity (Ι2 = 50.8%). When cancers diagnosed in the first year of SLE were excluded, the summary risk estimate was 1.25(95% CI, 1.10–1.43), otherwise, it increased (1.36; 95% CI, 1.14–1.63; S4 Fig). Both subgroups produced substantial heterogeneity (Ι2, 72.3% vs 56.6%). Males were at a higher risk to develop a cancer (pooled RR, 2.41; 95% CI, 1.46–3.98) than females (pooled RR, 1.62; 95% CI, 1.36–1.94; S5 Fig). Neither gender subgroup produced heterogeneity. Only the study [23] demonstrated that SLE population ≥ 50 years of age had a 1.60-fold cancer risk, the same as those <50 years of age. Two studies [23,24] evaluated SLE-duration-specific RRs and the pooled RRs were as follows: 2.21(95% CI, 1.71–2.85) for <1 y; 1.26 (95% CI, 1.07–1.47) for 1–4 y; 1.16 (95% CI, 0.86–1.55) for 5–9 y; 1.12 (95% CI, 0.89–1.41) for 10–19 y; and 1.43 (95% CI, 0.65–3.11) for 20+ y. There wasn’t heterogeneity between the two studies when it was less than 5 years since the diagnosis of SLE. The heterogeneity was moderate when it was 5–19 years. Considerable heterogeneity emerged when it was more than 20 years (Ι2 = 87.7%). Egger’s test was used to evaluate publication bias for the meta-analysis of overall malignancy. There was no apparent asymmetric distribution occurring in it (P = 0.055; Fig 4). When sensitivity analysis for the meta-analysis was executed, no significant change in pooled RR was found by sequential omission of individual studies, indicating that the result 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)

Relative risk of overall malignancy in patients with SLE compared with the general population.(N, number of patients with SLE; n, number of cancer cases).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0122964.g002: Relative risk of overall malignancy in patients with SLE compared with the general population.(N, number of patients with SLE; n, number of cancer cases).
Mentions: Of all included studies, fifteen, involving 58,077 patients with SLE, estimated RRs for overall malignancy. As shown in Fig 2, RR of each study ranged from 0.89–2.60 and the pooled RR by random effects analysis was 1.28 (95% CI, 1.17–1.41), with substantial heterogeneity (Ι2 = 57.6%). The Galbraith plot showed that three studies might be the major source of the heterogeneity (Fig 3), two conducted in Europe [9,23] and one in North America [13]. The regional subgroup analysis suggested that the European studies, as well as North American ones produced substantial heterogeneity (Ι2, 61.3% vs. 65.6%; Table 2). The pooled RRs in two areas were equally 1.37 (Table 2 and S1 Fig). We also performed subgroup analyses by study type, diagnostic criteria for SLE, whether cancers diagnosed in the first year of SLE being excluded, gender, and SLE duration (Table 2). As shown in S2 Fig, a higher risk of overall cancer was noted in the hospital-based cohorts (pooled RR, 1.33; 95% CI, 1.14–1.55) compared with the population-based ones (pooled RR, 1.29; 95% CI, 1.09–1.53). Considerable heterogeneity was found in the hospital-based subgroup (Ι2 = 75.8%), moderate heterogeneity in the population-based one (Ι2 = 45.4%). The studies adopting the American College of Rheumatology criteria for the classification of SLE (ACR, 1982)[32] conferred a lower risk to develop a cancer (pooled RR, 1.40; 95% CI, 1.19–1.65) than the study with 1971 criteria of American Rheumatism Association (ARA, 1971)[33] did (RR, 2.6; 95% CI, 1.5–4.4; S3 Fig). The cohorts with ACR criteria produced substantial heterogeneity (Ι2 = 50.8%). When cancers diagnosed in the first year of SLE were excluded, the summary risk estimate was 1.25(95% CI, 1.10–1.43), otherwise, it increased (1.36; 95% CI, 1.14–1.63; S4 Fig). Both subgroups produced substantial heterogeneity (Ι2, 72.3% vs 56.6%). Males were at a higher risk to develop a cancer (pooled RR, 2.41; 95% CI, 1.46–3.98) than females (pooled RR, 1.62; 95% CI, 1.36–1.94; S5 Fig). Neither gender subgroup produced heterogeneity. Only the study [23] demonstrated that SLE population ≥ 50 years of age had a 1.60-fold cancer risk, the same as those <50 years of age. Two studies [23,24] evaluated SLE-duration-specific RRs and the pooled RRs were as follows: 2.21(95% CI, 1.71–2.85) for <1 y; 1.26 (95% CI, 1.07–1.47) for 1–4 y; 1.16 (95% CI, 0.86–1.55) for 5–9 y; 1.12 (95% CI, 0.89–1.41) for 10–19 y; and 1.43 (95% CI, 0.65–3.11) for 20+ y. There wasn’t heterogeneity between the two studies when it was less than 5 years since the diagnosis of SLE. The heterogeneity was moderate when it was 5–19 years. Considerable heterogeneity emerged when it was more than 20 years (Ι2 = 87.7%). Egger’s test was used to evaluate publication bias for the meta-analysis of overall malignancy. There was no apparent asymmetric distribution occurring in it (P = 0.055; Fig 4). When sensitivity analysis for the meta-analysis was executed, no significant change in pooled RR was found by sequential omission of individual studies, indicating that the result 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