Cancer Susceptibility, Prognosis, and Hematological Malignancies Associated with Blood-Group Systems: A Biomolecular Systematic Review and Targeted Meta-Analysis

Abstract

Background: Blood-group antigens are inherited surface structures with roles extending beyond transfusion compatibility. ABO antigens are terminal glycans expressed on erythrocytes and many epithelial tissues, Duffy/ACKR1 regulates chemokine availability and leukocyte trafficking, and OK/BSG-CD147 participates in monocarboxylate-transporter stabilization, extracellular-matrix remodeling and tumour invasion. These biomolecular functions provide plausible links between blood-group biology and cancer susceptibility, prognosis and hematological malignancy, although the strength of epidemiological evidence varies by blood-group system and tumour site.

Methods: PubMed searches were conducted on 1 July 2026 using a broad blood-group/cancer strategy and focused queries for ABO, Rh, Duffy/ACKR1, OK/BSG-CD147, and review/meta-analysis literature. The PubMed phase retrieved 10,718 records, including 4,973 from the broad query and 5,745 from focused queries. After removal of 5,616 duplicate records, 5,102 unique records were available for title/abstract assessment. Evidence synthesis followed PRISMA 2020 and MOOSE reporting principles. A focused secondary random-effects meta-analysis was performed using published extractable estimates for ABO-A comparisons across cancer sites.

Results: The PubMed evidence set contained 94 review/meta-analysis candidates, 2,652 primary-study candidates, 2,028 biomolecular/mechanistic candidates and 764 hematological-malignancy candidates. Published pooled estimates consistently supported a modest risk signal for blood group A in several solid tumours. In the focused secondary random-effects synthesis of five published ABO-A estimates, the summary odds ratio was 1.22 (95% CI 1.13-1.32), indicating approximately 22% higher odds across the included published comparisons. Heterogeneity was high (I²=80.9%), meaning that the summary estimate should be interpreted as an evidence-landscape signal rather than a universal cancer-risk coefficient. Duffy/ACKR1 and OK/BSG-CD147 showed stronger biomolecular plausibility than population-level blood-typing evidence.

Conclusions: ABO has the strongest epidemiological support among blood-group systems, particularly in gastrointestinal and pancreatic cancer literature, whereas Duffy/ACKR1 and OK/BSG-CD147 are more strongly represented in mechanistic, immune-trafficking and tumour-metabolism studies. Blood group should not be used as a stand-alone clinical triage marker; its most defensible role is as a stratification variable in research models that already include age, sex, ancestry, tumour site, stage, infection status and treatment access.