The correlations between 91 inflammatory cytokines and malignant neoplasms of the stomach: an exploratory mendelian randomization analysis
- Journal of Cancer Prevention & Current Research
-
Hua Wang,1 Sisi Liu,2 Shaoyu
Xie,1 Yanping Yang,2 Sheng Li,1 Bo
Wen1
Abstract
Numerous
studies have suggested a possible link between inflammatory cytokines and
gastric malignancies; however, the causal relationships remain ambiguous. To
address this uncertainty, the present study utilized Mendelian randomization
(MR) to investigate the causal effects of inflammatory cytokine levels on the
development of malignant gastric neoplasms. Genetic variation datasets for
91 inflammatory cytokines were collected from genome-wide association studies (GWASs),
and information on malignant neoplasms of the stomach was obtained from the
Finnish database. The primary analysis was carried out via
the inverse variance weighted (IVW) method. To evaluate the robustness and
validity of the causal inferences, pleiotropy residual sum and outlier tests,
MR-Egger intercepts, Cochran's Q tests, and leave-one-out analyses were
conducted. Additionally, we utilized reverse MR to examine the possibility of
reverse causation. The IVW results indicated that the levels of interleukin-10
receptor subunit beta (IL-10RA) (OR = 1.1468; 95% CI: 1.0064-1.3068; P = 0.0398) and the levels of
tumor necrosis factor ligand superfamily member 14 (OR
= 1.1693;
95% CI: 1.0016-1.3651; P = 0.0476) increased the likelihood of a
high risk of malignant
neoplasm of the stomach, whereas matrix metalloproteinase-1 (MMP-1)
had a protective effect on the malignant neoplasm of the
stomach
(OR = 0.7813; 95% CI: 0.6125-0.9968; P = 0.0471). IL-10RA and MMP-1
were also validated in a subset of adenocarcinomas and papillary adenocarcinomas of the stomach. TNFSF14 and PD-L1 revealed
positive evidence to support causality with malignant neoplasms of the stomach and adenocarcinoma,
respectively. This study reveals potential associations
between 91 inflammatory cytokines and the risk of malignant gastric neoplasms,
as indicated by MR analysis. These findings provide important insights that may
facilitate the development of diagnostic biomarkers and aid in the
identification of novel therapeutic targets for gastric cancer.
Keywords
inflammatory cytokines, gastric malignant neoplasm, gastric adenocarcinoma, MR