Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, 677 Huntington avenue, Boston, MA, 02115, USA.
Department of Clinical Neurosciences, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
Cancer Causes Control. 2020 Mar;31(3):273-282. doi: 10.1007/s10552-020-01271-7. Epub 2020 Jan 31.
The relationship of allergic diseases, such as asthma, hay fever, and eczema, with cancer is under debate. Observational studies have reported conflicting findings, but such studies are susceptible to confounding and reverse causation. Understanding the potential role of allergy in carcinogenesis may shed new light on the biological mechanisms underpinning intrinsic immunity and cancer.
We conducted a Mendelian randomization study, using germline genetic variants as instrumental variables, to determine the causal relevance of allergic disease and on two most common malignancies: breast cancer and prostate cancer. We used the summary statistics from the largest ever genome-wide association studies conducted on allergic disease (n = 180,129), asthma (n = 14,085), breast (n = 122,977), and prostate cancer (n = 79,148) and calculated odds ratios (ORs) and 95% confidence intervals (CIs) of cancer for allergic disease.
We did not observe any evidence to support a causal association between allergic disease and risk of breast cancer overall [OR 1.00 (95% CI 0.96-1.04), p = 0.95] or by subtype (estrogen receptor (ER)+ [0.99 (0.95-1.04), p = 0.71], ER- [1.05 (0.99-1.10), p = 0.11]). We also did not find any evidence for an association with prostate cancer [1.00 (0.94-1.05), p = 0.93] or advanced subtype [0.97 (0.90-1.05), p = 0.46]. Sensitivity analyses did not reveal directional pleiotropy.
Our study does not support a causal effect of allergic disease on the risk of breast or prostate cancer. Future studies may be conducted to focus on understanding the causal role of allergic disease in cancer prognosis or drug responses (e.g., immunotherapy).
哮喘、花粉热和湿疹等过敏性疾病与癌症之间的关系仍存在争议。观察性研究报告的结果相互矛盾，但此类研究易受混杂因素和反向因果关系的影响。了解过敏在致癌作用中的潜在作用可能会为固有免疫和癌症的生物学机制提供新的认识。
我们进行了一项孟德尔随机化研究，使用种系遗传变异作为工具变量，以确定过敏性疾病与两种最常见的恶性肿瘤（乳腺癌和前列腺癌）之间的因果关系。我们使用最大的全基因组关联研究的汇总统计数据来研究过敏性疾病（n=180129）、哮喘（n=14085）、乳腺癌（n=122977）和前列腺癌（n=79148），计算了过敏疾病的癌症比值比（OR）和 95%置信区间（CI）。
我们没有观察到任何证据表明过敏性疾病与乳腺癌的总体风险之间存在因果关系[OR 1.00（95%CI 0.96-1.04），p=0.95]或按亚型[雌激素受体（ER）+[0.99（0.95-1.04），p=0.71]，ER- [1.05（0.99-1.10），p=0.11]）。我们也没有发现与前列腺癌[1.00（0.94-1.05），p=0.93]或晚期亚型[0.97（0.90-1.05），p=0.46]相关的证据。敏感性分析并未显示出方向性的混杂。
我们的研究不支持过敏性疾病与乳腺癌或前列腺癌风险之间存在因果关系。未来的研究可能集中在了解过敏性疾病在癌症预后或药物反应（例如免疫疗法）中的因果作用。
