http://www.biomedcentral.com/1741-7015/13/7
Commentary
The intriguing relationship between the ABO blood group, cardiovascular disease, and cancer
1
Department of Hematology and Transfusion Medicine, C. Poma Hospital,
Strada Lago Pajolo 10, Mantova, 46100, Italy
2 Laboratory of Clinical Chemistry and Hematology, Academic Hospital of Parma, Via Gramsci 14, Parma, 43100, Italy
2 Laboratory of Clinical Chemistry and Hematology, Academic Hospital of Parma, Via Gramsci 14, Parma, 43100, Italy
BMC Medicine 2015, 13:7
doi:10.1186/s12916-014-0250-y
The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/13/7
The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/13/7
Received: | 17 November 2014 |
Accepted: | 9 December 2014 |
Published: | 16 January 2015 |
© 2015 Franchini and Lippi; licensee BioMed Central.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Abstract
Other than being present at the surface of red blood cells, the antigens of the ABO
blood group system are efficiently expressed by a variety of human cells and tissues.
Several studies recently described the involvement of the ABO blood group in the pathogenesis
of many human disorders, including cardiovascular disease and cancer, so that its
clinical significance extends now beyond the traditional boundaries of transfusion
medicine. In a large cohort study recently published in BMC Medicine and including over 50,000 subjects, Etemadi and colleagues reported that nearly 6%
of total deaths and as many as 9% of cardiovascular deaths could be attributed to
having non-O blood groups, a condition that was also found to be associated with increased
risk of gastric cancer. In this commentary, the clinical implications of ABO blood
groups are critically discussed and a possible common pathogenic mechanism involving
the von Willebrand factor is described.
Please see related article http://dx.doi.org/10.1186/s12916-014-0237-8 webcite.
Keywords:
ABO blood group; Cancer; Cardiovascular disease; Mortality; von Willebrand factorBackground
The antigens of the ABO blood group system (i.e., A, B, and H antigens), discovered
more than one century ago [1], are complex carbohydrate molecules expressed on the extracellular surface of red
blood cell membranes [2]. The A and B alleles encode slightly different glycosyltransferases that add N-acetylgalactosamine
and D-galactose to a common precursor side chain, the H determinant, which is then
converted into A- or B-antigens, respectively (Figure 1). The O alleles do not encode a functional enzyme, so that OO carriers lack these
transferase enzymes and express the unaltered H structure, with a solitary terminal
fucose moiety attached to the precursor oligosaccharide chain, which represents the
phenotypic marker of the O blood group [3]. In addition to the expression on red blood cell surfaces, the ABO antigens are also
present in a variety of human cells and tissues, including epithelium, sensory neurons,
platelets, and vascular endothelium [4],[5]. Therefore, it is not surprising that the clinical significance of the ABO blood
group extends now beyond the traditional boundaries of immunohematology and transfusion
medicine, wherein this antigen system is seemingly involved in the pathophysiology
of a wide range of human diseases, the most important being represented by cancers
and infectious and cardiovascular disorders [6]-[9].
Figure 1. The intriguing relationship between ABO blood group system, von Willebrand factor
(VWF), cancer and cardiovascular disease.
Discussion
A number of studies conducted in the past 50 years have consistently described the
existence of an association between ABO blood type and cardiovascular disease [10]-[12]. In particular, a recent systematic review and meta-analysis documented that having
a non-O blood group carries an approximately two-fold increased risk of venous thrombosis
[10]. A weaker but still significant association was found in another systematic review
conducted by the same group of authors between non-O blood type and arterial thrombosis
(odds ratio [OR] of 1.28 for myocardial infarction and 1.17 for ischemic stroke) [11]. In addition to the effect of the ABO blood group on low-density lipoprotein and
total serum cholesterol levels [13], the leading underlying mechanism that has been put forward to explain this association
involves the profound influence that the ABO blood group system exerts on hemostasis,
particularly on the von Willebrand factor (VWF) and, consequently, on coagulation
factor VIII (FVIII) plasma levels, which are both well recognized prothrombotic risk
factors [14]. Indeed, it is now clearly acknowledged that individuals of non-O blood group status
have plasma levels of both VWF and FVIII that are approximately 25% higher than O
blood group subjects [15]. The molecular basis of this phenomenon has been precisely identified with the presence
of ABH antigenic structures on circulating VWF, which modulate the activity of this
multifunctional protein through different degrees of glycosylation [12].
Another interesting field that has been extensively studied over the past five decades
is that of the association between ABO blood group types and cancer [8],[9]. The most consistent association has been found with pancreatic and gastric cancers
[8]. For instance, in the Nurses’ Health Study and Health Professionals Follow-up Study,
Wolpin et al. [16] found that participants with blood groups A, AB, or B were more likely to develop
pancreatic cancer compared with those with blood group O (adjusted hazard ratio [HR]:
1.44; 95% CI: 1.14–1.82). The higher prevalence of blood group A in patients with
gastric cancer formerly observed by several studies [9] has also been recently confirmed in a large prospective population-based study involving
more than one million of Scandinavian blood donors followed for up to 35 years [17]. The strength of this association was similar to that previously reported (OR: 1.20;
95% CI: 1.02–1.42). Although the underlying mechanisms linking the ABO blood group
system and cancer are still largely unknown, one plausible explanation involves the
ABO blood group-driven regulation of circulating levels of several proinflammatory
and adhesion molecules (i.e., soluble E-selectin, P-selectin, and intercellular adhesion
molecule-1), which play a key role in the tumorigenesis process [9]. Moreover, the recent discovery that VWF is an important modulator of angiogenesis
and apoptosis provides an alternative, particularly intriguing, hypothesis to unify
the mechanisms by which non-O blood group influences the onset of cardiovascular and
neoplastic diseases (Figure 1) [18]. A significant advance in this field has now been provided by the Golestan Cohort
Study, recently published in BMC Medicine[19]. This large epidemiological trial analyzed the association between ABO blood groups
and overall and cause-specific mortality in over 50,000 people recruited between 2004
and 2008. Notably, the authors found that non-O blood groups were associated with
a significantly increased risk of total death (HR: 1.09; 95% CI: 1.01–1.17) and mortality
for cardiovascular disease (HR: 1.15; 95% CI: 1.03–1.27). Although no significant
association was found with ABO-related cancer mortality, an aspect that was investigated
for the first time in this study, an increased risk of developing gastric cancers
was still observed in individuals with blood groups A and B. This latter finding is
particular intriguing, and is also in keeping with the results from another recent
study conducted by our group, in which a negative association between B blood group
and life expectancy in a large cohort (n = 28,129) of subjects was found [20]. Although the analysis was only limited to overall mortality in our study, this evidence
may be attributable to the association between B blood type and some aging associated
conditions, including neurological and neoplastic disorders. Although additional research
is needed to corroborate these preliminary findings, the attractive data that have
emerged from these studies raise a new and intriguing scenario linking the ABO blood
group with cardiovascular disease and cancer (Figure 1).
Conclusions
Despite being studied for more than half a century, the complex interplay between
the ABO blood group system and human health is far from being definitely elucidated.
In particular, if the association between non-O blood type and cardiovascular disease
mortality is confirmed by further trials like that recently published by Etemadi et
al. [19], non-O blood group status may be included in cardiovascular risk scores to better
estimate the individual thrombotic risk profile. Further experimental studies are
also needed to unravel the molecular mechanisms linking ABO blood type, VWF, and cancer
development. Intuitively appealing, ABO blood typing may hence become part of a multifaceted
strategy for cancer risk assessment.
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From a more readable source:
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From a more readable source:
Cardiovascular Perks
Alexander
says that it does look as though blood type O is protective in the
setting of cardiovascular disease. “There is no reason to think that
particular molecules on red blood cells would have anything to do with
cardiovascular disease, but those same molecules attach molecules to a
protein that is important in blood clotting, called the Von Willebrand
factor,” she says. People with type O blood have lower Von Willebrand
factor levels. That’s good for the heart because ”it means your blood is
a little less likely to clot. And more heart attacks and strokes are
caused by blood clots, so anything that can have a part in reducing that
risk is beneficial.”
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