ABO blood group is a predictor of survival in patients with laryngeal cancer
In our study of 1260 patients with laryngeal cancer, we investigated the association between the ABO blood group and clinicopathologic characteristics and patient prognosis. We found no significant association between clinicopathologic characteristics and the ABO blood group. Univariate and multivariate analyses showed that the ABO blood group was significantly associated with the prognosis of patients with laryngeal cancer.
There are more than 100 recognized blood group systems composed of more than 500 antigens [7], of which the ABO blood group is considered the most important [8]. The ABO blood group is determined by the presence of A or B blood group antigens on the surface of red blood cells, which consist of proteins and carbohydrates attached to lipids or proteins. Red blood cell antigens have various functions, such as membrane structural integrity, transportation of molecules through membranes, and adhesion [9]. Along with their expression on red blood cells, ABO antigens are highly expressed on human tissues and most epithelial and endothelial cells [10, 11]. Since the first report by Aird et al. [12] that showed an association between blood group A and gastric cancer, the relationship between the ABO blood group and the risk, incidence, and clinicopathologic characteristics of human tumors has been suspected. Moreover, many studies have suggested a possible relationship between ABO blood group antigens and progression of human tumors [13–18]. Several plausible mechanisms, such as inflammation, immune-surveillance of malignant cells, and membrane signaling, have been proposed to explain this observed association between the ABO blood group and cancer risk [19]. Whereas the relationship between the ABO blood group and the incidence of laryngeal cancer remains unclear [4–6], the association between the ABO blood group and the risk of pancreatic cancer has been reported for over 40 years. Compared with people with blood group O, people with non-O blood groups have an adjusted hazard ratio (HR) for pancreatic cancer of 1.44 (95% confidence interval [CI] 1.14–1.82) [19]. Many studies have been conducted to examine the underlying mechanism of this relationship. For example, the multinational Pancreatic Cancer Cohort Consortium identified pancreatic cancer susceptibility loci in the ABO gene [20]. In this study, 1896 patients with pancreatic cancer and 1939 controls were genotyped, and a significant association was reported with rs505922, a single nucleotide polymorphism (SNP) that maps to the first intron of the ABO gene. The ABO SNP rs505922 is in strong linkage disequilibrium with O/non-O blood group alleles, indicating that people with non-O blood groups are at increased risk for developing pancreatic cancer [19, 21, 22]. In addition, two recent genome-wide association studies identified variants in ABO (rs505922), 1q32.1 (rs3790844), 13q22.1 (rs9543325), and 5p15.3 (rs401681) that were associated with a modestly increased risk of pancreatic cancer [23]. Two other studies suggested that the association between A blood group and increased risk of pancreatic cancer is due mainly to the A1 allele, thus indicating a direct connection between ABO glycosyltransferase activity and increased risk of this disease [24, 25]. Risch et al. [26] reported that the increased risk of pancreatic cancer among people with non-O blood groups was even higher if they were also seropositive for CagA-negative Helicobacter pylori (odds ratio: 2.78; 95% CI 1.49–5.20). Recently, Hofmann et al. [27] reported that healthy controls displayed significantly higher isoagglutinin titers and higher rate of binding to Tn and T antigen compared with patients with pancreatic ductal adenocarcinoma. Because Hofmann et al. [27] did not find an association between isoagglutinin titers and clinical parameters (such as OS and tumor stage), they assumed that isoagglutinins are important during tumorigenesis but not during actual tumor growth.
Our study showed, by both univariate and multivariate analyses, that the ABO blood group was an independent prognostic factor for patients with laryngeal cancer. Compared with patients with other ABO blood groups, patients with blood group O had significantly shorter OS.
There are only a few comparable studies in laryngeal cancer or in other types of head and neck cancer. A study by Ouyang et al. [28] indicated that nasopharyngeal carcinoma (NPC) patients with blood group A had significantly lower OS rate (adjusted HR = 1.49 [95% CI 1.03–2.17]) and distant metastasis-free survival rate (HR = 1.68 [95% CI 1.13–2.51]) than patients with non-A blood groups (B, AB, and O). In the subgroup analyses, they found that the increased risks associated with blood group A were restricted to men. Sheng et al. [17] conducted a case–control study and found that male NPC patients with blood group A had a significantly higher rate of distant metastasis than male patients with non-A blood groups (6.8% vs. 3.5%, P = 0.027), which directly supports the poorer prognosis of men with blood group A. A possible reason for the different results between laryngeal cancer and NPC is that NPC has a distinct epidemiology, etiology, and clinical manifestation compared with other head and neck cancers, including laryngeal cancer [29, 30].
Our findings are similar to those of previous studies in non-muscle invasive bladder urothelial carcinoma and locoregional esophageal squamous cell carcinoma (ESCC). Klatte et al. [31] found that non-muscle invasive bladder urothelial carcinoma patients with blood group O had higher recurrence and progression rates than patients with blood group A (P = 0.015 and 0.031, respectively) or blood group B (P = 0.004 and 0.075, respectively). In a subgroup analysis of 321 patients with ESCC who had ever smoked, Sun et al. [32] found that patients with blood group B/O had lower OS rate than patients with blood group A/AB (P = 0.024). For ESCC patients who had ever smoked, multivariate analysis showed an unfavorable and independent effect of blood group B/O on survival (P = 0.011). Our findings, however, are not in line with the findings of previous studies on pancreatic cancer, renal cell carcinoma, and curatively resected non–small cell lung cancer (NSCLC). For example, Engin et al. [33] and Rahbari et al. [34] found that pancreatic cancer patients with blood group O had a significantly longer survival than patients with non-O blood groups, regardless of prognostic factors. Kaffenberger et al. [35] showed that, in patients with renal cell carcinoma who underwent nephrectomy or partial nephrectomy, non-O blood groups were significantly associated with decreased OS (HR = 1.68, 95% CI 1.18–2.39, P = 0.004). Li et al. [36] showed that NSCLC patients with blood group O or B had significantly longer OS, disease-free survival, and local recurrence-free survival than NSCLC patients with blood group A or AB.
The results of studies evaluating the prognostic value of the ABO blood group in various cancers are quite conflicting. There are several possible explanations for the heterogeneity of findings across the studies. First, many studies were performed without the understanding that ABO frequencies can vary widely in populations assumed to be ethnically homogeneous; therefore, they included a limited number of patients and inappropriate control groups. Second, many studies were retrospective. Third, many recent studies that determined the association between the ABO blood group and the occurrence of malignant neoplastic disease are still preliminary or controversial, frequently not supported by strong statistical data. Underlying mechanisms still need to be explored or confirmed.
In our study, the distribution of the ABO blood group was similar to that in the Zhejiang [17] and Guangdong populations [32], with blood group O having the highest percentage (38.1%) and blood group AB having the lowest percentage (8.0%). It is still unclear why ABO blood groups affect the survival of patients with laryngeal cancer. Since no significant differences in the basic characteristics of patients with different ABO blood groups were observed, it is difficult to explain the effect of the ABO blood group. However, underlying molecular and pathogenic differences may play important roles in the effect of the ABO blood group on survival.
Our study had several limitations. First, it was conducted at a single center. Second, to detect an association between the ABO blood group and survival of patients with laryngeal cancer, we selected only the patients with locoregional disease that underwent curative treatment. Therefore, metastatic cases were excluded and not discussed. Third, despite the fact that the patients enrolled in this study mostly came from Guangdong province, some of them came from other areas in China. Fourth, worldwide, the general sex ratio (men:women) of laryngeal cancer is 8–10:1, but in our study, the ratio was 36.1:1. These limitations weaken the applicability of our data.
In conclusion, this study provides evidence of an association between the ABO blood group and survival of patients with laryngeal cancer: patients with blood group O had lower OS rate than patients with non-O blood groups. Further basic research on tumor genetic or biological differences associated with the ABO blood group is needed.