Shah Ami A, Igusa Takeru, Goldman Daniel, Li Jessica, Casciola-Rosen Livia, Rosen Antony, Petri Michelle
Division of Rheumatology, Johns Hopkins University School of Medicine, 5200 Eastern Avenue, Mason F. Lord Building Center Tower, Suite 4100, Baltimore, MD, 21224, USA.
Departments of Civil and Systems Engineering, Johns Hopkins University, 3400 North Charles Street, Latrobe Hall 212, Baltimore, MD, 21218, USA.
Arthritis Res Ther. 2021 Feb 25;23(1):64. doi: 10.1186/s13075-021-02449-3.
Epidemiologic data suggest that patients with systemic lupus erythematosus (SLE) have a lower risk of breast cancer than women in the general population. In light of mechanistic studies suggesting that anti-DNA antibodies have anti-cancer effects, we sought to examine breast cancer risk in autoantibody strata in a well-characterized SLE cohort.
SLE patients without a cancer diagnosis prior to entry in the Hopkins Lupus Cohort were studied (N = 2431). Overall and site-specific cancer incidence was calculated in racial strata and compared with the US Surveillance, Epidemiology and End Results (SEER) registry. Breast cancer incidence was further examined in autoantibody subsets. Patients were considered positive for an autoantibody if they were ever positive for a specificity during their disease course.
Patients with SLE had a 37% lower risk of breast cancer (SIR 0.63, 95% CI 0.39-0.95). The risk of HPV-associated cancers (SIR 4.39, 95% CI 2.87-6.44) and thyroid cancer (SIR 2.27, 95% CI 1.04-4.30) was increased. Cancer risk varied by race, with breast cancer protection occurring in non-African Americans (SIR 0.29, 95% CI 0.11-0.63) and the increased risk of HPV-associated cancers occurring in African Americans (SIR 7.23, 95% CI 4.35-11.3). Breast cancer risk was decreased in patients ever positive for anti-dsDNA (SIR 0.55, 95% CI 0.29-0.96), anti-La (SIR 0.00, 95% CI 0.00-0.78), and lupus anticoagulant (SIR 0.37, 95% CI 0.10-0.94). Patients who were positive for fewer (0-2) SLE autoantibodies did not have a lower risk of breast cancer (SIR 0.84, 95% CI 0.47-1.39), but patients with 3+ autoantibodies had a 59% decreased risk (SIR 0.41, 95% CI 0.16-0.84).
Positivity for multiple SLE autoantibodies was associated with a lower risk of breast cancer, supporting the hypothesis that a highly diversified immune response may exert an anti-cancer effect against some cancers. Validation of racial differences in cancer risk in SLE is required to determine whether cancer screening strategies should be targeted to racial subgroups.
流行病学数据表明，系统性红斑狼疮（SLE）患者患乳腺癌的风险低于普通人群中的女性。鉴于机制研究表明抗DNA抗体具有抗癌作用，我们试图在一个特征明确的SLE队列中研究自身抗体分层中的乳腺癌风险。
对入组霍普金斯狼疮队列前未被诊断患有癌症的SLE患者进行研究（N = 2431）。计算种族分层中的总体和特定部位癌症发病率，并与美国监测、流行病学和最终结果（SEER）登记处的数据进行比较。进一步研究自身抗体亚组中的乳腺癌发病率。如果患者在病程中某一特异性自身抗体曾呈阳性，则被视为该自身抗体阳性。
SLE患者患乳腺癌的风险降低37%（标准化发病比[SIR] 0.63，95%置信区间[CI] 0.39 - 0.95）。人乳头瘤病毒（HPV）相关癌症（SIR 4.39，95% CI 2.87 - 6.44）和甲状腺癌（SIR 2.27，95% CI 1.04 - 4.30）的风险增加。癌症风险因种族而异，非裔美国人中存在乳腺癌保护作用（SIR 0.29，95% CI 0.11 - 0.63），而非洲裔美国人中HPV相关癌症风险增加（SIR 7.23，95% CI 4.35 - 11.3）。抗双链DNA（dsDNA）抗体曾呈阳性（SIR 0.55，95% CI 0.29 - 0.96）、抗La抗体（SIR 0.00，95% CI 0.00 - 0.78）和狼疮抗凝物曾呈阳性（SIR 0.37，95% CI 0.10 - 0.94）的患者乳腺癌风险降低。自身抗体阳性数量较少（0 - 2种）的患者患乳腺癌的风险并未降低（SIR 0.84，95% CI 0.47 - 1.39），但自身抗体阳性数量≥3种的患者风险降低59%（SIR 0.41，95% CI 0.16 - 0.84）。
多种SLE自身抗体呈阳性与较低的乳腺癌风险相关，支持高度多样化的免疫反应可能对某些癌症发挥抗癌作用这一假说。需要对SLE患者癌症风险的种族差异进行验证，以确定癌症筛查策略是否应针对不同种族亚组。
