In this study, we conducted a meta-analysis to clarify the relationship between ABO SNPs (rs505922 and rs657152) and cancer/cardiocerebrovascular diseases risk. Our results showed that these two SNPs were associated with pancreatic cancer risk and also increased the risk of cardiocerebrovascular diseases.
Regarding to rs505922 SNP, our results showed that the variant type of rs505922 could increase the risk of overall cancer, suggesting a potential predictive ability of this SNP for cancer risk. When we conducted a subgroup analysis of rs505922 based on cancer sites and ethnicity, we found that there was no significant association between rs505922 and Non-pancreatic cancer subgroup or Caucasian subgroup. This result may be due to heterogeneity of cancer types or insufficient statistical power. Therefore, further studies with large samples size are warrant to evaluate the association between the rs505922 polymorphisms in Non-pancreatic cancers. On the other side, our data also showed that rs505922 was associated with cardiocerebrovascular diseases. In subgroup analysis, we found that there was no association between rs505922 and cardiocerebrovascular diseases in Asian subgroup. Only two studies with small population were included in this analysis, further studies are needed in Asian population. The SNP is located in the first intron region of ABO gene, the protective T allele of rs505922 is in complete linkage disequilibrium (r2 = 1.0) with the O allele, is marks of O allele. However, the regulatory mechanism underlying the expression of histoblood group antigens was unclear.
For rs657152, our study demonstrated that this SNP was associated with cancer/ cardiocerebrovascular diseases risk. However, only eight studies [12–15, 17, 20, 30, 31] were reported and most of studies were conducted in Caucasian population. Therefore, more studies with different ethnic background and larger sample size are needed in the future. Rs657152 is located in the intron area of ABO, the possible function has not been revealed yet. Rs657152 has been found to be associated with several biological molecule, including LDL cholesterol [36], liver derived alkaline phosphatas [37], and IL-6 [38]. This implied that rs657152 may affect the occurrence and development of disease by influencing these biological molecule. Further subsequent functional studies are warrant.
The underlying mechanism for the relationship between ABO blood group and cancer risk is still poorly understood [39]. It is reported that blood type may affect the progression and expansion of malignant tumors by altering the systemic inflammatory response [40]. Recent studies reported an association between polymorphisms at the ABO gene locus and circulating levels of tumour necrosis factor-alpha [41], soluble intercellular adhesion molecule (ICAM)-1 [42, 43], E-selectin [44, 45], and P-selectin [43]. These adhesion molecules were important mediators of chronic inflammation and immune cell recruitment [46]. They may provide a biological basis for the postulated influence of ABO on cancer survival, by linking ABO blood group and tumour initiation and spread [39]. In addition, some researches have shown that the structure of certain tumor antigens was similar to the structure of antigens of ABO blood group system. Smith and Prieto [47] suggested the Forssmann antigen which predominant in stomach and colon tumors, was almost structurally identical to the A antigen determinant. Blood group A carrier may have diminished tumor immune response due to reduced ability to recognize and attack tumor cells [48].
There was some evidence linking ABO blood group and cardiocerebrovascular diseases. Jenkins, P.V. et al. reported an association between ABO blood types and von Willebrand factor(vWF) and factor VIII(FVIII), both of which play crucial roles in the coagulation pathway [49]. Higher levels of vWF and FVIII has been observed in non-O blood type than O blood type [50]. Therefore, type O blood may be a risk factor for bleeding [51]. In addition, the non-O blood group has been shown to be correlated with higher total cholesterol and LDL-C levels[52], and the latest study proposed that approximately 10% of the effect of ABO blood group on coronary artery disease (CAD) susceptibility was mediated by plasma cholesterol levels[53].
Limitations in this study should be mentioned. First, the studies included in our meta-analysis were limited to published reports and English language studies. Unpublished reports or those published in non-English language studies were not included in the analysis. It would limit our sample size and publication bias might be exist. Second, both of the hospital based and population based case-control studies were included in our study. Therefore, selection bias would be exist compared to the meta-analysis only included population based case-control studies. Third, the limited number of published studies may influence the reliability of our results. Finally, the lack of original data limited further evaluations of the potential gene-gene and gene-environment interactions.