Red Cells and Cancer I: ABO Blood Type and Risk for Pancreatic Cancer
Abstract & Commentary
By William B. Ershler, MD
Synopsis: In an evaluation of two large cohort studies (the Nurses' Health Study and the Health Professionals Follow-up Study), there was a slightly increased risk of pancreatic cancer in those with blood groups A, B, and AB relative to those with blood group O, such that approximately 17% of pancreatic cancer cases were attributable to the non-O blood group.
Source: Wolpin BM, et al. ABO blood group and the risk of pancreatic cancer. J Natl Cancer Inst. 2009;101:424-431.
The fact that genetic factors may play a role in the development of pancreatic cancer has long been suspected because of the small, but definite, increased risk of this disease among first-degree relatives.1,2 Furthermore, pancreatic cancer is associated with several genetic syndromes, including hereditary breast and ovarian cancer, familial atypical multiple mole melanoma syndrome (FAMMM), Peutz -Jeghers syndrome, and hereditary pancreatitis.3,4 However, these genetic syndromes, and other established risk factors, account for only a minority of pancreatic cancer cases, and the predisposing environmental and genetic factors for most patients remain unknown.
ABO blood type is an inherited characteristic that, in previous small studies, has been associated with increased risk of gastrointestinal malignancies, including pancreatic cancer.5-7 However, studies of pancreatic cancer were limited by their retrospective design and small case numbers. Human blood group antigens are glycoproteins expressed on the surface of red blood cells and several other tissue types, including cells from the gastrointestinal tract. The sugar residues of these glycoproteins are attached to a protein backbone, the H antigen, by a glycosyltransferase encoded for by the ABO gene on chromosome 9q34. In laboratory investigations, patient-derived pancreatic cancer cells express blood group antigens on their cell surface and have different patterns of expression than cells in adjacent normal pancreatic ducts, suggesting that modifications to glycosyltransferase specificity occur during pancreatic tumorigenesis. Alterations in surface glycoconjugates may lead to modifications in intercellular adhesion, membrane signaling, and immunosurveillance, which could have important implications for tumor development and spread. Nevertheless, the association between ABO blood type and the risk of pancreatic cancer has not been rigorously, nor prospectively, evaluated.
To address this, Wolpin et al examined the relationship between ABO blood type and the risk of incident pancreatic cancer in two large, independent, prospective cohort studies (the Nurses' Health Study and Health Professionals Follow-up Study) that collected blood group data from 107,503 U.S. healthcare professionals. Hazard ratios for pancreatic cancer by ABO blood type were calculated using Cox proportional hazards models, with adjustment for other known risk factors, including age, tobacco use, body mass index, physical activity, and history of diabetes mellitus.
During 927,995 person-years of follow-up, 316 participants developed pancreatic cancer. ABO blood type was associated with the risk of developing pancreatic cancer (p = .004; log-rank test). Compared with participants with blood group O, those with blood groups A, AB, or B were more likely to develop pancreatic cancer (adjusted hazard ratios for incident pancreatic cancer were 1.32 [95% confidence interval {CI} = 1.02 to 1.72], 1.51 [95% CI = 1.02 to 2.23], and 1.72 [95% CI = 1.25 to 2.38], respectively). The association between blood type and pancreatic cancer risk was nearly identical in the two cohorts (p interaction = .97). Overall, 17% of the pancreatic cancer cases were attributable to inheriting a non-O blood group (blood group A, B, or AB). The age-adjusted incidence rates for pancreatic cancer per 100,000 person-years were 27 (95% CI = 23 to 33) for participants with blood type O, 36 (95% CI = 26 to 50) for those with blood type A, 41 (95% CI = 31 to 56) for those with blood type AB, and 46 (95% CI = 32 to 68) for those with blood type B.
Commentary
Thus, in two large, independent populations, ABO blood type was statistically, significantly associated with the risk of pancreatic cancer. Whether this association is directly or indirectly related to the pathogenesis of the disease remains speculative, but it is notable that, in addition to their expression on the surface of red blood cells, the ABO antigens are highly expressed on the surface of epithelial cells of the gastrointestinal, bronchopulmonary, and urogenital tracts.8 Pathology studies have demonstrated the novel expression of A, B, and H antigens on the surface of pancreatic cancer cells compared with surrounding normal ductal cells,9 suggesting that alterations in glycosyltransferase specificity may occur during pancreatic tumorigenesis. This is of relevance because glycoconjugates are important mediators of intercellular adhesion and membrane signaling, two processes integral to malignant progression and spread. In addition, these surface molecules are recognized by the host-immune response and may have a role in facilitating immunosurveillance for malignant cells.
Although there are certain limitations inherent in a study that relies on self report and includes a population of limited diversity, the overall large size of the study population, its prospective design and statistical methodology support the general concept that ABO blood group status may represent a common, partially penetrant, inherited susceptibility for pancreatic cancer. Further studies are necessary to define the mechanisms by which ABO blood type, or closely linked genetic variants, may influence pancreatic cancer risk.
References
1. Schenk M, et al. Familial risk of pancreatic cancer. J Natl Cancer Inst. 2001;93:640-644.
2. McWilliams RR, et al. Risk of malignancy in first-degree relatives of patients with pancreatic carcinoma. Cancer. 2005;104:388-394.
3. Lochan R, et al. Genetic susceptibility in pancreatic ductal adenocarcinoma. Br J Surg. 2008;95:22-32.
4. Hezel AF, et al. Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev. 2006;20:1218-1249.
5. Newell GR, et al. ABO blood groups and cancer. J Natl Cancer Inst. 1974;52:1425-1430.
6. Vioque J, Walker AM. [Pancreatic cancer and ABO blood types: a study of cases and controls]. Med Clin (Barc). 1991;96:761-764.
7. Annese V, et al ABO blood groups and cancer of the pancreas. Int J Pancreatol. 1990;6:81-88.
8. Hakomori S. Antigen structure and genetic basis of histo-blood groups A, B and O: Their changes associated with human cancer. Biochim Biophys Acta. 1999; 1473:247-266.
9. Pour PM, et al. Expression of blood group-related antigens ABH, Lewis A, Lewis B, Lewis X, Lewis Y, and CA 19-9 in pancreatic cancer cells in comparison with the patient's blood group type. Cancer Res. 1988; 48:5422-5426.
In an evaluation of two large cohort studies (the Nurses' Health Study and the Health Professionals Follow-up Study), there was a slightly increased risk of pancreatic cancer in those with blood groups A, B, and AB relative to those with blood group O, such that approximately 17% of pancreatic cancer cases were attributable to the non-O blood group.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content