ABO Blood Type Has No Impact on Survival in Patients with Endometrial Carcinoma – A cohort study of 1074 patients

Background: Endometrial carcinoma is one of the three major malignant tumors in gynecology. ABO blood type is associated with the prognosis of a variety of malignancies. This study assessed the relationship between ABO blood type and prognosis of endometrial carcinoma. Methods: We retrospectively analyzed the relationship between ABO blood type and endometrial carcinoma prognosis in patients with primary endometrial carcinoma who underwent surgery from Shengjing Hospital aliated to China Medical University from January 2012 to February 2017. Univariate analysis, multivariate analysis, and stratied analysis were performed. Results: In the multivariate analysis, 2009 FIGO stage (HR=2.806, 95% CI=1.289, 6.109), Pathological tissue type (HR=0.199, 95% CI=0.079, 0.503) was an independent and important risk factor for OS. We divided the ABO blood type into A and non-A groups, B and non-B groups, O and non-O groups, AB and non-AB groups, and failed to measure the signicant results of OS. After we excluded 9 patients who had recurrence, metastasis, or death within 1 year of enrollment, the OS-signicant results were similar to those described above. Conclusions: Our study suggest that there is no association between ABO blood type and EC prognosis, and additional cohort studies are needed for validation. survival with early stage disease or advanced diagnosis. 1900. A absence and on the surface of red blood cells. According to distribution of agglutinogens A and B, four A, B, AB, and O. of O ABO blood types and the survival of Chinese patients with resected NSCLC. And the overall survival, patients-free survival and locoregional relapse-free survival were signicantly prolonged in patients with a blood group of O or B compared with patients with blood group A or AB.


Introduction
Endometrial carcinoma (EC) is one of the three major malignant tumors in gynecology. In the United States, there are 61,880 new cases each year, second only to breast cancer, lung and bronchial cancer, and colorectal cancer. There are 12,160 deaths, second only to lung and bronchial cancer, breast cancer, colorectal cancer, pancreatic cancer and Ovarian cancer, ranked sixth. [1] The most important risk factors in EC are obesity, persistent endogenous or exogenous hyperestrogen (polycystic ovary, tamoxifen treatment, anovulation and nulliparity), hypertension and diabetes. Moreover, women with Lynch syndrome (LS or hereditary non-colon cancer) have a signi cantly increased risk of developing EC. Most patients with EC have a good prognosis, but have a survival rate of less than 50% for patients with high-risk early stage disease or advanced diagnosis. [2] The ABO blood group system is the rst blood type system discovered and determined by Landsteiner in 1900. A blood type system classi ed according to the presence or absence of speci c antigens (aggregates) A and B on the surface of red blood cells. According to the distribution of agglutinogens A and B, blood is divided into four types: A, B, AB, and O. Studies have shown that the risk of diffuse gastric cancer in patients with type A blood is increased by 20% compared with people with type O blood, [3] people with type A blood have an increased risk of breast cancer. [4,5] In addition, studies have shown that patients with type B or AB blood have lower survival rates and increased risk of recurrence after breast cancer. [6] Chang et al. showed that type A blood is associated with a higher incidence and metastatic rate of malignant melanoma of the skin, [7] blood type B It also signi cantly reduced the risk of stomach cancer and bladder cancer, while blood type AB signi cantly increased the risk of liver cancer. [8] Moreover, studies have shown that ABO blood type has no effect on the survival of patients with epithelial ovarian cancer. [9] Previous studies have shown that regardless of menopausal status, body mass index, oral contraceptive use or family cancer history, blood group A is positively associated with EC risk in Chinese women [10] . To investigate the relationship between ABO blood group and prognosis of EC, we conducted a retrospective study at Shengjing Hospital of China Medical University.

Data collection
According to the electronic medical records of the electronic information system of Shengjing Hospital a liated to China Medical University, we collected the following demographic and clinical variables: age of diagnosis, menopause, birth history, degree of tumor differentiation, 2009 FIGO stage, Depth of in ltration(layer), lymphatic vessel interstitial in ltration, Lymph node metastasis, pathological tissue types, etc. At the same time, the blood type of the patient before the operation was obtained through the Shengjing Hospital inspection system. All data were collected by experienced gynaecologists and pathologists.
Tumor staging was calculated according to the 2009 International Obstetrics and Gynecology Alliance (FIGO) staging standard. The degree of differentiation of tumors is divided into high differentiation, high-medium differentiation, medium differentiation, medium-low differentiation, and low differentiation. The depth of in ltration(layer) is divided into mucosal layers, less than 1/2, greater than or equal to 1/2. According to the pathological tissue type, it is divided into adenocarcinoma and non-adenocarcinoma 2.3 Follow-up and outcome

Statistical analysis
The Chi-square test was used to compare continuous and categorical variables in different blood types, respectively. Age at diagnosis is summarized as means±SD. Follow-up time is summarized as the median of the inter-quartile range (IQR). The categorical variables are expressed as numbers and percentages. The Cox proportional hazard model was used to estimate risk ratios (HRs) and 95% con dence intervals (CIs). We use the likelihood ratio test to assess the proportional hazard assumption. The ABO blood type is divided into four groups: A, B, O, and AB. In addition, we conducted the following four subgroups, group A and non-group A, group B and non-group B, group O and non-group O, group AB and non-group AB.
At the same time, we performed Multivariable adjusted analyses, including the following potential confounders: age at diagnosis, menopause, birth history, degree of tumor differentiation, FIGO stage, Depth of in ltration(layer), lymphatic vessel in ltration, Lymph node metastasis, pathological tissue type. In addition, we conducted a subgroup analysis of strati cation of potential confounding factors by appeal. A likelihood ratio test was performed to check whether the association between ABO blood group and OS was modi ed by the following pre-speci ed potential effect modi ers: menopause, birth history, degree of tumor differentiation, FIGO stage, Depth of in ltration(layer), lymphatic vessels Interstitial in ltration, Lymph node metastasis, pathological tissue type. We further excluded by sensitivity analysis: patients with recurrence, metastasis, or patients who died within 1 year of study enrollment. P value <0.05 was considered statistically signi cant. All analyses were performed using the IBM SPSS Statistics 24 software.

Patient characteristics
As shown in Figure 1, information of variables and covariates were incomplete after the exclusion, a total of 1074 patients were included in the study. Among them, 17 patients had recurrence, 30 patients had metastasis, and 40 patients died. The demographic and clinical characteristics of patients with EC according to ABO blood type are shown in Table     At the same time, we excluded the 9 patients who had recurrence, metastasis or death within 1 year, and the OS signi cant results were similar to the above results.

Discussion
Page 9/11 The ABO blood type is the most important blood type system in the human blood group system. The ABO gene is located on chromosome 9q34 and encodes two alleles of speci c glycosyltransferases, namely A and B. [11] The blood group antigen is a secondary gene product, and the primary gene product is a various glycosyltransferase that binds a sugar molecule to an oligosaccharide chain. [12] The ABO gene consists of 7 exons of more than 20KB of genomic DNA, and two key single base substitutions in the nal coding exon result in amino acid substitutions, which result in a donor between A-transferase and B-transferase. The difference in nucleotide sugar substrate speci city. [13] The blood group O does not have the glycosyltransferase encoded by the A and B genes, and expresses a fucosylated variant (Ley) of the precursor structure. [14] Studies have shown that ABO blood group plays an important role in affecting circulating sP-selectin and sICAM-1 levels, which may be related to glycosylation of Pselectin/ICAM-1 from cell membrane detachment interaction. [15] At present, multiple studies have shown that ABO blood group is associated with tumor prognosis. Cao et al [16] showed that Blood type AB is a favourable prognostic factor for patients with colon cancer. Studies by DONATAS STAKIŠAITIS have shown that type B blood is associated with prostate cancer and bladder cancer risk and can be assessed as a determinant of negative longevity. [17] A study by Ting Jin et al [18] showed that the OS of patients with blood group O was signi cantly shorter than that of other ABO patients. In addition, prospective studies have shown that type B and type AB blood are associated with a signi cant reduction in the risk of gastrointestinal and colorectal cancer, respectively, and type B blood reduces the risk of stomach cancer and bladder cancer, and type AB blood increases liver cancer. The risk, but not related to the risk of sarcoma, lymphoma, leukemia or other cell types of cancer. [8] A retrospective study by Li et al showed that there is an association between the ABO blood types and the survival of Chinese patients with resected NSCLC. And the overall survival, patients-free survival and locoregional relapse-free survival were signi cantly prolonged in patients with a blood group of O or B compared with patients with blood group A or AB. [19] There are currently few studies on ABO blood type and EC. A retrospective cohort study of 203 patients with type I EC found that patients with type A blood had a lower risk of developing G3 tumors than patients with non-type A blood. [20] Type A blood is associated with a high risk of EC [21] , whereas conversely, A case-control study of 440 patients with EC showed that the ABO blood group was not associated with the risk of EC. [22] Based on this, we have 1074 patients from Shengjing Hospital a liated to China Medical University from January 2012 to February 2017. A retrospective study was conducted and a large number of subgroup analyses were performed. Multivariate analysis showed that histological type was an independent and important risk factor for OS, while other factors were not signi cantly associated with OS. At the same time, we divided the ABO blood type into A group and non-A group, B group and non-B group, O group and non-O group, AB group and non-AB group respectively for strati ed analysis, no signi cant interaction, further we Sensitivity analysis was performed on patients who had relapsed, metastasized, and died within 1 year of enrollment. OS outcomes were similar. For our study, the sample size was larger compared to previous studies related to ABO blood group and EC. Moreover, our sample information comes from Shengjing Hospital a liated to China Medical University, and its electronic medical record system is perfect, thereby minimizing the likelihood of recall bias. On the other hand, our study had a short follow-up period (median follow-up period was year), and the number of missing dependent variables and covariates was 1032. However, we found no difference between the patients included and excluded.

Conclusion
In summary, our data suggest that there is no association between ABO blood type and EC prognosis, and additional cohort studies are needed to validate. and Outstanding Scienti c Fund of Shengjing Hospital (No. 201601). The funding body had no involvement in the design of the study, collection, analysis, interpretation of data or in writing the manuscript.