Zhang Min, Wang Yizhou, Wang Yutong, Bai Ye, Gu Dongqing
School of Public Health and Management, Chongqing Medical University, Chongqing, China.
Department of Pathology, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, China.
Front Oncol. 2022 May 4;12:860794. doi: 10.3389/fonc.2022.860794. eCollection 2022.
Observational studies suggested that systemic lupus erythematosus (SLE) might be associated with increased cancer incidence and cancer-related death, however, the results are inconsistent. We aim to comprehensively estimate the causal relationships between SLE and cancer morbidity and mortality using a meta-analysis of cohort studies and Mendelian randomization.
A systematic search was conducted using PubMed to identify cohort studies published before January 21, 2021. Meta-analysis was performed to calculate relative risk (RR) and corresponding 95% confidence intervals (CI). In addition, we further evaluated the potentially causal relationships identified by cohort studies using two-sample Mendelian randomization.
A total of 48 cohort studies involving 247,575 patients were included. We performed 31 main meta-analysis to assess the cancer risk and three meta-analyses to evaluate cancer mortality in SLE patients. Through meta-analyses, we observed an increased risk of overall cancer (RR=1.62, 95%CI, 1.47-1.79, <0.001) and cancer-related death (RR=1.52, 95%CI, 1.36-1.70, <0.001) in patients with SLE. Subgroup analysis by site-specific cancer showed that SLE was a risk factor for 17 site-specific cancers, including six digestive cancers (esophagus, colon, anus, hepatobiliary, liver, pancreatic), five hematologic cancers (lymphoma, Hodgkin's lymphoma, non-Hodgkin lymphoma, leukemia, multiple myeloma), as well as cancer in lung, larynx, cervical, vagina/vulva, renal, bladder, skin, and thyroid. In addition, further mendelian randomization analysis verified a weakly association between genetically predisposed SLE and lymphoma risk (odds ratio=1.0004, =0.0035).
Findings from our study suggest an important role of SLE in carcinogenesis, especially for lymphoma.
https://www.crd.york.ac.uk/PROSPERO/, CRD42021243635.
观察性研究表明，系统性红斑狼疮（SLE）可能与癌症发病率和癌症相关死亡增加有关，然而，结果并不一致。我们旨在通过队列研究的荟萃分析和孟德尔随机化来全面评估SLE与癌症发病率和死亡率之间的因果关系。
使用PubMed进行系统检索，以识别2021年1月21日前发表的队列研究。进行荟萃分析以计算相对风险（RR）和相应的95%置信区间（CI）。此外，我们使用两样本孟德尔随机化进一步评估队列研究确定的潜在因果关系。
共纳入48项队列研究，涉及247,575例患者。我们进行了31项主要荟萃分析以评估癌症风险，3项荟萃分析以评估SLE患者的癌症死亡率。通过荟萃分析，我们观察到SLE患者的总体癌症风险增加（RR = 1.62，95%CI，1.47 - 1.79，<0.001）和癌症相关死亡风险增加（RR = 1.52，95%CI，1.36 - 1.70，<0.001）。按特定部位癌症进行的亚组分析表明，SLE是17种特定部位癌症的危险因素，包括6种消化系统癌症（食管、结肠、肛门、肝胆、肝脏、胰腺）、5种血液系统癌症（淋巴瘤、霍奇金淋巴瘤、非霍奇金淋巴瘤、白血病、多发性骨髓瘤），以及肺癌、喉癌、宫颈癌、阴道/外阴癌、肾癌、膀胱癌、皮肤癌和甲状腺癌。此外，进一步的孟德尔随机化分析证实了遗传易感性SLE与淋巴瘤风险之间的弱关联（优势比 = 1.0004，P = 0.0035）。
我们的研究结果表明SLE在致癌过程中起重要作用，尤其是对淋巴瘤。
