观察性研究已经探讨了干燥综合征（Sjögren's syndrome，SS）与某些癌症之间的关联，然而，因果关系仍不清楚。我们使用Mendelian随机化（Mendelian randomization，MR）方法研究了SS与不同类型癌症之间的因果关系。我们在欧洲人群中使用公共基因组关联研究（genome-wide association studies, GWASs）汇总统计数据进行了两样本Mendelian随机化，以评估SS与九种癌症之间的因果关系。样本量从1080到372,373不等。我们使用倒置方差加权（inverse variance weighted, IVW）方法来估计因果效应。研究中明确了Bonferroni校正的P值阈值为P < 0.0031，P值在0.0031和0.05之间被认为暗示着相关性。我们进行了敏感性分析以验证因果关系。此外，我们还进行了附加分析，评估了SS与被广泛接受的癌症风险因素之间的关联。在校正了异质性和水平不等基因效应之后，结果表明，患有SS的患者与淋巴瘤的风险显著相关（比值比[odds ratio, OR] = 1.0010，95%置信区间[confidence interval, CI]：1.0005-1.0015，P = 0.0002），与前列腺癌的风险降低（OR = 0.9972，95% CI：0.9960-0.9985，P = 2.45 x 10-5）和子宫内膜癌（OR = 0.9414，95% CI：0.9158-0.9676，P = 1.65 x 10-5）也呈现显著相关关系。在肝胆管癌（OR = 0.9999，95% CI：0.9997-1.0000，P = 0.0291）和泌尿道癌（OR = 0.9996，95% CI：0.9992-1.0000，P = 0.0281）中发现了暗示性关联。SS对其他癌症类型没有因果作用。附加的MR分析表明，SS与癌症之间的因果关系并不是通过广泛接受的癌症风险因素介导的。未观察到SS对癌症的因果关联证据。SS与淋巴瘤、前列腺癌和子宫内膜癌有显著的因果关系，并在肝胆管癌和泌尿道癌中找到了暗示性的相关证据，这表明SS在这些恶性肿瘤的发生中可能起到重要作用。© 2023. BioMed Central Ltd., part of Springer Nature.

Several observational studies have explored the associations between Sjögren's syndrome (SS) and certain cancers. Nevertheless, the causal relationships remain unclear. Mendelian randomization (MR) method was used to investigate the causality between SS and different types of cancers.We conducted the two-sample Mendelian randomization with the public genome-wide association studies (GWASs) summary statistics in European population to evaluate the causality between SS and nine types of cancers. The sample size varies from 1080 to 372,373. The inverse variance weighted (IVW) method was used to estimate the causal effects. A Bonferroni-corrected threshold of P < 0.0031 was considered significant, and P value between 0.0031 and 0.05 was considered to be suggestive of an association. Sensitivity analysis was performed to validate the causality. Moreover, additional analysis was used to assess the associations between SS and well-accepted risk factors of cancers.After correcting the heterogeneity and horizontal pleiotropy, the results indicated that patients with SS were significantly associated with an increased risk of lymphomas (odds ratio [OR] = 1.0010, 95% confidence interval [CI]: 1.0005-1.0015, P = 0.0002) and reduced risks of prostate cancer (OR = 0.9972, 95% CI: 0.9960-0.9985, P = 2.45 × 10-5) and endometrial cancer (OR = 0.9414, 95% CI: 0.9158-0.9676, P = 1.65 × 10-5). Suggestive associations were found in liver and bile duct cancer (OR = 0.9999, 95% CI: 0.9997-1.0000, P = 0.0291) and cancer of urinary tract (OR = 0.9996, 95% CI: 0.9992-1.0000, P = 0.0281). No causal effect of SS on other cancer types was detected. Additional MR analysis indicated that causal effects between SS and cancers were not mediated by the well-accepted risk factors of cancers. No evidence of the causal relationship was observed for cancers on SS.SS had significant causal relationships with lymphomas, prostate cancer, and endometrial cancer, and suggestive evidence of association was found in liver and bile duct cancer and cancer of urinary tract, indicating that SS may play a vital role in the incidence of these malignancies.© 2023. BioMed Central Ltd., part of Springer Nature.