Personal history of irradiation and risk of breast cancer: A Mendelian randomisation study.

Background: Studies on the relationship between personal history of irradiation and breast cancer have been reported for a long time. Still, epidemiological studies have not been conclusive, and the causal relationship is unclear. To address this issue, we employed Mendelian randomisation (MR) analysis to examine the association between individual radiation exposure history and breast cancer.

Methods: We used a series of quality control methods to select single nucleotide polymorphism (SNP) closely related to exposure. Meanwhile, several analysis methods were used to analyse the sample data to make the conclusion more reliable. To evaluate the horizontal pleiotropy, heterogeneity and stability of SNPs for breast cancer, the MR-Egger intercept test, Cochran's Q test and 'leave one' sensitivity analysis were used. Finally, the outlier variation determined by the Mendelian Randomisation Pleiotropy RESidual Sum and Outlier test is gradually eliminated to reduce the influence of heterogeneity and horizontal pleiotropy.

Results: After implementing rigorous quality control procedures, we carefully chose 102 qualified instrumental variables closely associated with the selected exposure for sensitivity analysis. This was conducted to evaluate the heterogeneity, level multiplicity, and stability of SNPs in the context of personal radiation history and its correlation with breast cancer. The results of the inverse variance weighted method analysis revealed a positive correlation between personal radiation and a heightened risk of breast cancer (odds ratio (OR) = 1.52; 95% confidence interval (CI) = 1.30-1.77). We also validated on another data set; the results were similar (OR = 1.51; 95% CI = 1.27-1.81). Furthermore, the findings from the sensitivity analysis were consistent. At the genetic level, our research demonstrated that personal radiation exposure is associated with an elevated risk of breast cancer.

Conclusions: Using genetic data provides evidence and strengthens the causal link that personal radiation causes breast cancer.