Genetic association of plasma homocysteine levels with gastric cancer risk：a two-sample Mendelian randomization study
Menée à l'aide d'une méthode de randomisation mendélienne et des données de deux études d'association sur le génome entier portant sur 2 631 patients atteints d'un cancer gastrique et sur 4 373 témoins, cette étude analyse l'association entre le taux plasmatique d'homocystéine et le risque de développer la maladie
Background : The association of plasma homocysteine level (PHL) with gastric cancer (GC) risk was reported in observational studies. However, the causality is challenging due to confounding factors and the lack of evidence from well-designed cohort studies. Herein, we performed a two-sample Mendelian randomization (MR) analysis to investigate whether PHL is causally related to GC risk. Methods : We performed the MR analysis based on the results from genome-wide association studies (GWAS) consisting of 2631 GC patients and 4373 controls. An externally weighted genetic risk score (wGRS) was constructed with 15 single nucleotide polymorphisms (SNPs) with well-established associations with PHL. We utilized logistic regression model to estimate associations of PHL-related SNPs and wGRS with GC risk in total population and in strata by sex, age and study site, in addition to a series of sensitivity analyses. Results : High genetically predicted PHL was associated with an increased GC risk (per standard deviation (SD) increase in the wGRS: OR=1.07, 95% CI: 1.01-1.12, P=0.011), which was consistent in sensitivity analyses. Subgroup analyses provided evidence of a stronger association with GC risk in women than in men. MR-Egger and weighted median regression suggested that potentially unknown pleiotropic effects were not biasing the association between PHL and GC risk. Conclusions : These results revealed that genetically predicted high PHL was associated with an increased GC risk, suggesting that high PHL may have a causal role in the etiology of GC. Impact : These findings provide causal inference for PHL on GC risk, suggesting a causal role of high PHL in the etiology of GC.