He Ming-Ming, Lo Chun-Han, Wang Kai, Polychronidis Georgios, Wang Liang, Zhong Rong, Knudsen Markus D, Fang Zhe, Song Mingyang
Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
JAMA Oncol. 2022 Feb 1;8(2):209-219. doi: 10.1001/jamaoncol.2021.5680.
Immune regulation is important for carcinogenesis; however, the cancer risk profiles associated with immune-mediated diseases need further characterization.
To assess the prospective association of 48 immune-mediated diseases with the risk of total and individual cancers and the prospective association of organ-specific immune-mediated diseases with the risk of local and extralocal cancers.
DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study used data from the UK Biobank cohort study on adults aged 37 to 73 years who were recruited at 22 assessment centers throughout the UK between January 1, 2006, and December 31, 2010, with follow-up through February 28, 2019.
Immune-mediated diseases.
The association of immune-mediated diseases with risk of cancer was assessed with multivariable hazard ratios (HRs) and 95% CIs after adjusting for various potential confounders using time-varying Cox proportional hazards regression. Heterogeneity in the associations of organ-specific immune-mediated diseases with local and extralocal cancers was assessed using the contrast test method.
A total of 478 753 participants (mean [SD] age, 56.4 [8.1] years; 54% female) were included in the study. During 4 600 460 person-years of follow-up, a total of 2834 cases of cancer were documented in 61 496 patients with immune-mediated diseases and 26 817 cases of cancer in 417 257 patients without any immune-mediated diseases (multivariable HR, 1.08; 95% CI, 1.04-1.12). Five of the organ-specific immune-mediated diseases were significantly associated with higher risk of local but not extralocal cancers: asthma (HR, 1.34; 95% CI, 1.14-1.56), celiac disease (HR, 6.89; 95% CI, 2.18-21.75), idiopathic thrombocytopenic purpura (HR, 6.94; 95% CI, 3.94-12.25), primary biliary cholangitis (HR, 42.12; 95% CI, 20.76-85.44), and autoimmune hepatitis (HR, 21.26; 95% CI, 6.79-66.61) (P < .002 for heterogeneity). Nine immune-mediated diseases were associated with an increased risk of cancers in the involved organs (eg, asthma with lung cancer [HR, 1.34; 95% CI, 1.14-1.57; P < .001] and celiac disease with small intestine cancer [HR, 6.89; 95% CI, 2.18-21.75; P = .001]); 13 immune-mediated diseases were associated with an increased risk of cancer in the near organs (eg, Crohn disease with liver cancer: [HR, 4.01; 95% CI, 1.65-9.72; P = .002]) or distant organs (eg, autoimmune hepatitis with tongue cancer [HR, 27.75; 95% CI, 3.82-199.91; P = .001]) or in different systems (eg, idiopathic thrombocytopenic purpura with liver cancer [HR, 11.96; 95% CI, 3.82-37.42; P < .001]).
In this cohort study, immune-mediated diseases were associated with an increased risk of total cancer. Organ-specific immune-mediated diseases had stronger associations with risk of local cancers than extralocal cancers. The associations for individual immune-mediated diseases were largely organ specific but were also observed for some cancers in the near and distant organs or different systems. Our findings support the role of local and systemic immunoregulation in cancer development.
免疫调节对癌症发生至关重要；然而，与免疫介导疾病相关的癌症风险特征仍需进一步明确。
评估48种免疫介导疾病与总体癌症及个体癌症风险的前瞻性关联，以及器官特异性免疫介导疾病与局部和非局部癌症风险的前瞻性关联。
设计、设置和参与者：这项前瞻性队列研究使用了英国生物银行队列研究的数据，研究对象为年龄在37至73岁之间的成年人，于2006年1月1日至2010年12月31日期间在英国22个评估中心招募，随访至2019年2月28日。
免疫介导疾病。
在使用时间变化的Cox比例风险回归对各种潜在混杂因素进行调整后，通过多变量风险比（HR）和95%置信区间（CI）评估免疫介导疾病与癌症风险的关联。使用对比检验方法评估器官特异性免疫介导疾病与局部和非局部癌症关联的异质性。
共纳入478753名参与者（平均[标准差]年龄为56.4[8.1]岁；54%为女性）。在4600460人年的随访期间，61496名患有免疫介导疾病的患者中共记录了2834例癌症病例，417257名无任何免疫介导疾病的患者中共记录了26817例癌症病例（多变量HR为1.08；95%CI为1.04 - 1.12）。五种器官特异性免疫介导疾病与局部癌症风险升高显著相关，但与非局部癌症无关：哮喘（HR为1.34；95%CI为1.14 - 1.56）、乳糜泻（HR为6.89；95%CI为2.18 - 21.75）、特发性血小板减少性紫癜（HR为6.94；95%CI为3.94 - 12.25）、原发性胆汁性胆管炎（HR为42.12；95%CI为20.76 - 85.44）和自身免疫性肝炎（HR为21.26；95%CI为6.79 - 66.61）（异质性P <.002）。九种免疫介导疾病与受累器官癌症风险增加相关（例如，哮喘与肺癌[HR为1.34；95%CI为1.14 - 1.57；P <.001]，乳糜泻与小肠癌[HR为6.89；95%CI为2.18 - 21.75；P =.001]）；13种免疫介导疾病与临近器官（例如，克罗恩病与肝癌：[HR为4.01；95%CI为1.65 - 9.72；P =.002]）或远处器官（例如，自身免疫性肝炎与舌癌[HR为27.75；95%CI为3.82 - 199.91；P =.001]）或不同系统（例如，特发性血小板减少性紫癜与肝癌[HR为11.96；95%CI为3.82 - 37.42；P <.001]）的癌症风险增加相关。
在这项队列研究中，免疫介导疾病与总体癌症风险增加相关。器官特异性免疫介导疾病与局部癌症风险的关联比与非局部癌症的关联更强。个体免疫介导疾病的关联在很大程度上具有器官特异性，但在一些临近和远处器官或不同系统的癌症中也有观察到。我们的研究结果支持局部和全身免疫调节在癌症发展中的作用。
