Abstract
ObjectiveThe purpose of this paper is to examine cancer incidence in patients with ANCA-associated vasculitis (AASV) derived from population-based cohort studies by means of meta-analysis.MethodsRelevant electronic databases were searched for studies characterizing the associated risk of overall malignancy in patients with AASV. Standardized incidence rates (SIRs) with 95% confidence intervals (CIs) were used to evaluate the strength of association. We tested for publication bias and heterogeneity and stratified for site-specific cancers.ResultsSix studies (n = 2,578) were eventually identified, of which six provided the SIR for overall malignancy, five reported the SIR for non-melanoma skin cancer (NMSC), four for leukemia, five for bladder cancer, three for lymphoma, three for liver cancer, four for lung cancer, three for kidney cancer, four for prostate cancer, four for colon cancer and four for breast cancer. Overall, the pooled SIR of cancer in AASV patients was 1.74 (95%CI = 1.37–2.21), with moderate heterogeneity among these studies (I2 = 65.8%, P = 0.012). In sub-analyses for site-specific cancers, NMSC, leukemia and bladder cancer were more frequently observed in patients with AASV with SIR of 5.18 (95%CI = 3.47–7.73), 4.89 (95%CI = 2.93–8.16) and 3.84 (95%CI = 2.72–5.42) respectively. There was no significant increase in the risk of kidney cancer (SIR = 2.12, 95%CI = 0.66–6.85), prostate cancer (SIR = 1.45, 95%CI = 0.87–2.42), colon cancer (SIR = 1.26, 95%CI = 0.70–2.27), and breast cancer (SIR = 0.95, 95%CI = 0.50–1.79). Among these site-specific cancers, only NMSC showed moderate heterogeneity (I2 = 55.8%, P = 0.06). No publication bias was found by using the Begg’s test and Egger's test.ConclusionsThis meta-analysis shows that AASV patients treatment with cyclophosphamide (CYC) are at increased risk of late-occurring malignancies, particularly of the NMSC, leukemia and bladder cancer. However, there is no significant association between AASV and kidney cancer, prostate cancer, colon cancer and breast cancer. These findings emphasize monitoring and preventative management in AASV patients after cessation of CYC therapy is momentous.
Highlights
The anti-neutrophil cytoplasm antibody associated vasculitides (AASVs), including graulomatosis with polyangiitis (GPA, Wegener’s granulomatosis) and microscopic polyangiitis (MPA), are a group of multisystem disorders characterized by necrotizing inflammation of small blood vessels[1]
The pooled standardized incidence rate (SIR) of cancer in AASV patients was 1.74 (95%confidence interval (CI) = 1.37–2.21), with moderate heterogeneity among these studies (I2 = 65.8%, P = 0.012)
In sub-analyses for site-specific cancers, non-melanoma skin cancer (NMSC), leukemia and bladder cancer were more frequently observed in patients with AASV with SIR of 5.18 (95%CI = 3.47–7.73), 4.89 (95%CI = 2.93–8.16) and 3.84 (95%CI = 2.72–5.42) respectively
Summary
The anti-neutrophil cytoplasm antibody associated vasculitides (AASVs), including graulomatosis with polyangiitis (GPA, Wegener’s granulomatosis) and microscopic polyangiitis (MPA), are a group of multisystem disorders characterized by necrotizing inflammation of small blood vessels[1]. 25–50% of the patients will relapse[6], leading to increased duration and quantity of CYC which would cause toxic effects especially for cardiovascular and cancer morbidity[7]. The latter has drawn more attention recently. Much effort has been devoted to this field which demonstrated the SIRs for overall cancer has increased to more than 1.6 associated with AASV[6,8–13], but the risk of overall cancer appeared to be somewhat reduced in one study (SIR = 0.8, 95%CI = 0.5–1.4)[14]. Given the fact that individual studies may have insufficient statistical power because of sample size, we undertook the present meta-analysis to quantitatively confirm the incidence of cancer in AASV patients versus the general population, which may provide a realistic perspective on risk in the clinical setting
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