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Microbes & Immunity ABO blood type and cancer risk: A complex relationship

Numerous studies have reported associations between galactosyltransferase, which transfers D-galactose to the
blood types and cancer susceptibility. A relationship H determinant. However, the O-variant allele encodes a
between the A blood group and gastric cancer was first non-functional glycosyltransferase and is characterized by
demonstrated in 1953. Since then, a higher incidence of a single base pair deletion at base pair 261, resulting in the
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the A blood group has been documented in numerous loss of enzyme translation and unmodified H antigen. 18,19
cancers, such as colon, ovarian, and cervical cancers. As Thus, the carbohydrate moieties present on the surface
cells become malignant, they tend to lose normal blood of the erythrocyte’s membrane define ABO blood group
antigens and gain new tumor-associated antigens. The antigens. Besides red blood cells, the expression of ABO
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reduction in normal antigens (A, B, and H) is inversely antigens is also observed on the surface of various human
proportional to the metastatic ability of the tumor. cells and tissues, such as vascular endothelium, platelets,
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Some tumor antigens are true A antigens, while others are sensory neurons, mucus secretions, and epithelial tissues. 21
A-like antigens, sharing properties similar to A antigens.
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Therefore, these antigens can be detected on the tumors of 1.1.2. Immune response
patients with blood type A, as they would be recognized as Blood group antigens are considered primarily tissue
foreign antigens, triggering an immune attack. However, antigens distributed throughout the body. The rejection
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A or A-like antigens present in tumors are not perceived of transplanted organs and natural abortions is caused
as foreign in individuals with the A blood group. This by antibodies produced against these antigens. ABO
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may explain why individuals with the A blood group have antigens expressed in normal tissues have been reported
a higher risk of cancer than those with blood group O. 15,16 to be different from those expressed in cancerous cells. 23,24
This review attempts to decipher the correlation between This difference is assumed to alter cell motility, apoptosis,
the frequency of blood groups and the incidence of and immune escape. The ABO blood type system is linked
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different cancers. to several diseases including cancer in humans based on
the presence or absence of those antigens throughout the
1.1. Mechanism of the pathology body. 26,27 However, the underlying phenomena associated
1.1.1. Glycosyltransferase activity with the risk of ABO variants with tumor development and
The ABO blood grouping system involves antigens, progression remain unclear and have become the subject
including A, B, and H. The ABO system comprises of research.
seven exons containing DNA variants that alter the A possible assumption is that malignancy is induced
enzymatic activity of the gene (Figure 1). The gene for by the dysregulation of the enzymatic activity of ABO
the ABO blood group is located on chromosome 9q34, glycosyltransferases that play major roles in intercellular
which encodes alleles A and B, resulting in specific adhesion, cell membrane signaling, and host immune
glycosyltransferases produced from four non-synonymous response. 28-31 This mechanism is similar to the process
variants at nucleotides 526, 703, 796, and 803. The A by which ABO glycosyltransferases regulate circulating
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allele encodes α1-3 N-galactosaminyltransferase, which plasma levels of von Willebrand factor (Figure 2), which
catalyzes the covalent linkage of N-acetylgalactosamine was recently discovered as an important regulator
to the non-reducing ends of glycans on the glycoproteins of angiogenesis and apoptosis in tumorigenesis. 32-34
of the H antigen expressed in all red blood cells. The B Alternation in the host inflammatory system and systemic
allele encodes another glycosyltransferase called α1-3- inflammatory response may also influence blood group

Figure 1. Structure of the ABO gene locus showing the nucleotide sequences of the A, B, and O alleles 17
Abbreviations: a.a., amino acid; bp, base pair; nt, nucleotide position.

Volume 2 Issue 1 (2025) 46 doi: 10.36922/mi.3267