Recent research has shown a connection between circulating blood cell traits and the occurrence of EC[9]. However, the majority of existing studies are observational and may be influenced by external factors. In this analysis using Mendelian randomization, genetic data from a GWAS meta-analysis was used to assess the potential causal link between circulating blood cell characteristics and the risk of EC.This study provides new evidence that altered circulating blood traits are associated with EC susceptibility.
Circulating blood cell traits have been shown to have a significant correlation with the risk of developing certain types of cancer, including lung cancer, breast cancer, and gastric cancer[16]. In EC, changes in specific blood cell traits may be strongly associated with susceptibility and prognosis [9]. Our findings support and expand upon existing observational evidence, highlighting the significant role of certain blood cell traits in the pathophysiology of EC.BAS, a type of leukocyte, can traverse the capillary wall and localize to sites of bacterial invasion to combat infections by surrounding, engulfing, and destroying the pathogens. An increase in BAS counts is often linked to allergic diseases, hematological disorders, malignant tumors, and infectious diseases.[17].In a prior observational investigation, a correlation was discovered between elevated preoperative BAS counts in blood of patients with EC and the prognosis of EC[18]. Prior to surgery, lower counts of preoperative BAS were associated with advanced tumor staging and were determined as an autonomous risk element for unfavorable recurrence-free survival (RFS). In cases of EC, individuals with low BAS counts showed a greater predisposition to hematogenous metastasis in contrast to individuals with elevated BAS counts. However, our research proposes that an elevation in BAS counts in the bloodstream could indeed escalate the incidence of EC, contradicting prior results. This discrepancy could be attributed to potential confounding factors in observational studies that may lead to biased results. HBG is a crucial protein responsible for transporting oxygen in red blood cells, giving blood its characteristic red color.[19]. Hemoglobin levels are commonly used as a marker in blood tests and changes in its levels can indicate various health conditions like anemia[20], pulmonary heart disease[21], and cancers[22]. A previous 12-year cohort study revealed a link between anemia and increased risk of cancers like esophageal, gastric, and breast cancers.[9].Additionally, the study showed that esophageal cancer patients with high HBG levels prior to surgery had a longer survival time[23].Our Mendelian randomization analysis aligns with previous observational studies suggesting that hemoglobin levels may lower the risk of EC.
The reverse analysis results revealed that EC has the potential to reduce LYM counts in the bloodstream, aligning with the findings of an earlier observational study. The diminished lymphocyte counts in individuals with EC might be attributed to extended tumor length, advanced T stage, a weight loss of ≥ 3 kg and body mass index of ≤ 18.5 kg/m2 within the preceding 3 months[24]. In addition, the reduced number of LYM severely affected their response to therapy, survival, prognosis, and toxicity [25]. Additionally, our research uncovered a correlation between EC and the reduction in MPV. While there is a lack of empirical evidence demonstrating a direct link between EC and a decline in MPV, a separate study indicated a marked difference in 5-year overall survival (OS) and recurrence-free survival (RFS) rates between individuals with high MPV and those with low MPV. This study ultimately concluded that elevated MPV served as a stand-alone prognostic indicator for both OS and RFS outcomes[8].
There are some strengths to our study.Firstly, studies on circulating blood cell traits in patients with EC are very limited, and most of the extant studies are observational. This study is the first to explore the connection between circulating blood cell traits and EC using a large-scale GWAS dataset and MR analysis. By utilizing this method, our findings are more trustworthy compared to observational studies. Additionally, the study's validity was confirmed through the use of an extensive database, stringent adjustments for numerous comparisons, and convenient examination of gene expression in human specimens.However,there are several restrictions in our research.Firstly, our investigation was carried out with a European population and did not encompass other demographics, thus restricting its generalizability. Secondly, we utilized summarized statistical information instead of individual-level data, which impedes our capacity to delve deeper into causal connections among different groups, like males and females. Additionally, the genetic information in the GWAS repository lacks specific disease stages, patient age, and associated medical conditions, preventing us from conducting thorough subgroup analyses.