Stratified analyses of associations between E-DII quintiles and PC by genotype-derived ABO blood type did not show interaction by blood type (Pinteraction = 0.10 in PanC4 and Pinteraction=0.13 in PanScan).
Our study demonstrates that pancreatic cancer risk is influenced by ABO status, in particular blood groups O and A<sub>1</sub> , and that this association may reflect also in tumor resectability and survival.
Consistent with assessment using a false discovery rate approach, significant associations with ABO blood group were observed for cancer of the pancreas, breast, and upper gastrointestinal tract (mouth, salivary glands, pharynx, esophageal adenocarcinoma and stomach).
Recently, one single nucleotide polymorphism (SNP) rs505922 in ABO gene has been implicated in susceptibility to pancreatic cancer across different populations, but different results were found in other types of cancer.
Our results are compatible with the previously reported association between the ABO gene and pancreatic cancer, and show that the effect of these common variants at the ABO locus on the P-LIP and ACE levels is largely opposing and pleiotropic.
Since glycosyltransferase activity, encoded by ABO, is higher for the A1 variant compared with the A2 variant, we investigated the hypothesis that A1 carriers were at an increased risk of pancreatic cancer.
These infections may contribute to the progression of pancreatic cancer by acting jointly with other pancreatic cancer risk factors that impact the inflammation and immune response, such as smoking and obesity, and the ABO genetic variant, recently linked to pancreatic cancer through genome-wide association studies.
We suspect that ABO genotype/phenotype status influences the behavior of H. pylori which in turn affects gastric and pancreatic secretory function, and these ultimately influence the pancreatic carcinogenicity of dietary- and smoking-related N-nitrosamine exposures, and thus risk of pancreatic cancer.
LKM test identified four genes that were significantly associated with risk of pancreatic cancer after Bonferroni correction (P<1×10(-5)): ABO, HNF1A, OR13C4, and SHH.
Genome-wide association studies have conclusively linked the ABO locus to pancreatic cancer, venous thromboembolism, and myocardial infarction in the presence of coronary atherosclerosis.
These consist of high penetrance genes including BRCA2 or PALB2, to more common genetic variation associated with a modest increase risk of pancreatic cancer such as genetic variation at the ABO blood group locus.
Single nucleotide polymorphisms (SNPs) in ABO, sonic hedgehog (SHH), telomerase reverse transcriptase (TERT), nuclear receptor subfamily 5, group A, member 2 (NR5A2) were found to be associated with pancreatic cancer risk.
It is noteworthy that 2 recent genome-wide association studies of pancreatic cancer have reported that variants in ABO blood type and in 3 other chromosomal regions are associated with risk for this cancer, thus providing new insight into pancreatic cancer etiology.
These data support the hypothesis that ABO glycosyltransferase activity influences pancreatic cancer risk rather than actions of other nearby genes on chromosome 9q34.
The associations of the ABO blood group gene and NR5A2 gene variants with PC discovered by recent genome-wide association studies may link insulin resistance, inflammation, and thrombosis to pancreatic carcinogenesis.