Abstract 1230P
Background
Epidemiology evidences have demonstrated that Behçet's disease (BD) may be associated with increased risk of several types of cancer. However, conventional observational studies are susceptible to potential confounders and inverse causation. In addition, the causal effects between BD and cancers remain unknown.
Methods
11 single nucleotide polymorphisms (SNPs) in BD were identified as reaching genome-wide significance (p < 5×10-8) and were thus retrieved from latest published genome-wide association studies (GWASs). Available genetic data on different types of cancer were extracted from several consortia or published studies, including the International Lung Cancer Consortium (ILCCO, 11, 348 cases and 15, 861 controls), Breast Cancer Association Consortium (BCAC, 122, 977 cases and 105, 974 controls) and so on. With two-sample Mendelian randomization (MR) analysis, study-specific estimates were summarized using inverse-variance-weighted (IVW), weighted median and MR-Egger methods. MR-Egger regression was conducted to evaluate the pleiotropy. Leave-one-out analysis was employed to appraise whether the MR estimate was biased by a single SNP.
Results
MR analysis indicated that BD patients were at lower risks of lung cancer (OR = 0.972, 95% CI: 0.947-0.996, p = 0.024), tongue cancer (OR = 0.999, 95% CI: 0.999-1.000, p = 0.004), penile cancer (OR = 0.999, 95% CI: 0.999-1.000, p = 0.030) and brain cancer (OR = 0.999, 95% CI: 0.999-1.000, p = 0.035) (Table). MR-Egger regression suggested the absence of directional horizontal pleiotropy. Leave-one-out results shown that by omitting the included 11 SNPs singly, no individual genetic variants appeared to have any significant effect on the overall results. Table: 1230P
Mendelian randomization estimates of the causal effect of genetically Behçet's disease on different types of cancer
| Cancer type | IVW | MR-Egger | Weighted median | |||
| OR (95% CI) | p-value | OR (95% CI) | p-value | OR (95% CI) | p-value | |
| Lung cancer | 0.972 (0.947, 0.996) | 0.024 | 0.955 (0.921, 0.951) | 0.050 | 0.963 (0.938, 0.998) | 0.004 |
| Breast cancer | 0.996 (0.987, 1.005) | 0.383 | 0.998 (0.982, 1.013) | 0.773 | 0.997 (0.987, 1.006) | 0.480 |
| Tongue cancer | 0.999 (0.999, 1.000) | 0.004 | 1.000 (1.000, 1.000) | 0.097 | 1.000 (1.000, 1.000) | 0.004 |
| Penile cancer | 0.999 (0.999, 1.000) | 0.030 | 1.000 (1.000, 1.000) | 0.160 | 1.000 (1.000, 1.000) | 0.807 |
| Brain cancer | 0.999 (0.999, 1.000) | 0.035 | 1.000 (0.999, 1.000) | 0.163 | 0.999 (0.999, 1.000) | 0.075 |
Conclusions
BD was causally correlated with reduced risk of lung cancer, brain cancer, tongue cancer and penile cancer, suggesting autoimmune or autoinflammatory etiopathology associated with BD activity might play a role in the suppression of cancer development.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
China National Science Foundation (Grant No. 81871893); Key Project of Guangzhou Scientific Research Project (Grant No. 201804020030); Cultivation of Guangdong College Students' Scientific and Technological Innovation (“Climbing Program” Special Funds) (Grant No. pdjh2020a0480).
Disclosure
All authors have declared no conflicts of interest.