Our study demonstrates that pancreatic cancer patients treated at a large, US institution are significantly more likely to be blood group A than regional blood donors and are significantly less likely to be blood group O than regional blood donors; the proportions of patient vs donor ABO blood groups were statistically different from what would be expected by chance alone. We examined this relationship among over 700 000 unique individuals who made blood donations to the Central Blood Bank in Pittsburgh between 1979 and 2009. Although there was a trend for risk of pancreatic adenocarcinoma in association with blood groups B and AB, a statistically significant effect was not observed, likely due to limited study power for detecting differences in these small subpopulations of individuals.
In a prospective cohort study published in 2009 of 107 503 US residents derived from the Nurses’ Health Study (77 360 eligible female nurses) and the Health Professionals Follow-up Study (30 143 eligible male health professionals), individuals with blood group A, B and AB were noted overall to have an elevated risk of pancreatic cancer compared to those participants with blood group O[8
]. However, taking each study separately, only blood group B was associated with increased cancer risk. Notably, blood group was self-reported in that prospective study, although a validation analysis displayed a greater than 90% concordance rate between reported and actual ABO blood group. In our study, the presence of serologically-determined blood group information from the blood bank was an entry criterion; thus, there was no possibility of recall bias influencing our results.
locus is located on chromosome 9 and there are three main alleles in the system: A101
, and O01
]. The A101
allele encodes a glycosyltransferase that adds a terminal α-N-acetylgalactosamine to H antigen, producing the A antigen. Similarly the B101
allele encodes a glycosyltransferase that adds a terminal α-D-galactose to H antigen, thus creating the B antigen. The most common types of O
alleles contain a critical 1-bp deletion compared to the consensus A101
allele and, if translated, would give rise to non-functional enzymes[10,11
]. In a group O individual, the H antigen is not modified. In addition to studies of pancreatic cancer, numerous past studies have shown that blood group A is related to gastric cancer[12,13
]. The precise biological reasons as to why there is a relationship between ABO blood group and certain cancers are unknown, although two recent GWAS demonstrated that particular SNPs at the ABO
locus were associated with the inflammatory cytokines tumor necrosis factor[14
] and intercellular adhesion molecule 1[15
]. The ABO blood group has also been shown to be related to other biological processes; for example, although a definitive mechanism has not yet been elucidated, levels of von Willebrand factor (vWF) antigen have been statistically shown to correlate to the ABO group with group AB individuals demonstrating the highest average vWF levels and group O individuals having the lowest average vWF levels[16
The ABO blood group is genetically-determined and therefore is not a modifiable risk factor as are cigarette smoking, body mass index, diet or other lifestyle-related variables. The risk of pancreatic cancer for individuals with blood group A has been replicated in several studies. Nonetheless, the magnitude of risk is not high enough to warrant clinical screening, especially considering that these approaches are still in the developing stages[17
]. However, the risk of pancreatic cancer in individuals with blood group A (and likely B or AB) is nearly as strong as the risk of developing pancreatic cancer as a consequence of cigarette smoking; thus, the combination of multiple moderate risk factors (such as age and family history[18
]) could be used to calculate whether some individuals are at high enough risk to warrant counseling for risk reduction strategies or inclusion in pancreatic cancer screening trials.
The importance of the ABO blood group in assessing pancreatic cancer risk is also highlighted by the lack of other global genetic risk factors identified in the GWAS by Amundadottir et al[9
]. This study indicates that the etiology of pancreatic cancer is more complex than previously believed and likely represents an array of deleterious pathways. Although the mechanisms of pancreatic cancer oncogenesis have not been fully deciphered, the association of ABO blood group with pancreatic cancer risk has been confirmed.