Allergy, asthma, and the risk of breast and prostate cancer: a Mendelian randomization study

Abstract

Purpose 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. Methods 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 case = 180,129), asthma (n case = 14,085), breast (n case = 122,977), and prostate cancer (n case = 79,148) and calculated odds ratios (ORs) and 95% confidence intervals (CIs) of cancer for allergic disease. Results 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. Conclusion 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).

Instrumental Heterogeneity in Sex-Specific Two-Sample Mendelian Randomization: Empirical Results From the Relationship Between Anthropometric Traits and Breast/Prostate Cancer

“…When using sex-specific instruments, various sensitivity analyses also should be carried out to ensure the robustness of the results. Third, when only sex-combined summary statistics are available and one has to apply sex-combined IVs for exposures, explaining possible biases in the causal inference due to sex instrumental heterogeneity is strongly advocated ( Au Yeung and Schooling, 2019 ; Jiang et al, 2020 ; Papadimitriou et al, 2021 ).…”

Investigating asthma heterogeneity through shared and distinct genetics: Insights from genome-wide cross-trait analysis

“…In such situations, we suggest conducting the Mendelian randomization by using multiple methods as a sensitivity analysis. 56 If multiple methods arrive at a similar conclusion, then we would consider the results robust. However, when the conclusions reached by using these methods do not agree, we recommend close comparisons of their results, including for consistency of the direction for causal effect estimates, the magnitude of the effect, and the statistical significance (related to the power and sample size).…”

Current status and perspectives regarding the association between allergic disorders and cancer

“…Another approach to evaluate the relationship between allergies and cancer is “Mendelian Randomization,” which uses a functional genetic variation as an instrumental variable to investigate the association between modifiable exposures and disease 96 . A Mendelian randomization study did not show any causal relationship between allergic disease and risk of BC overall (OR = 1.00; 95% CI: 0.96–1.04) or by subtype (estrogen receptor [ER] positive (OR = 0.99; 95% CI: 0.95–1.04), and ER negative (OR = 1.05; 95% CI: 0.99–1.10) 97 …”