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Risk of Pancreatic Cancer Linked to Variation in Gene that Determines Blood Type

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Common variants of the gene that determines human blood type are associated with an increased risk of pancreatic cancer, according to a study by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health, and colleagues from many universities and research institutions.

The study, published online Aug. 2, 2009, in Nature Genetics, is consistent with an observation first made more than 50 years ago.

In the study, the researchers discovered that genetic variation in a region of chromosome 9 that contains the gene for ABO blood type was associated with pancreatic cancer risk. Individuals with the variant that results in blood types A, B, or AB were at an increased risk of pancreatic cancer, compared to those with the variant for blood type O.

This finding is consistent with previous research, some of it dating back to the 1950s and 1960s, that had shown increased risks of gastric and pancreatic cancer among individuals of the A and B blood groups. The latest results provide a genetic basis for those earlier observations.

A person's blood type depends on which form or forms of the ABO gene they inherit from their parents. The protein produced by the ABO gene determines the type of carbohydrates (complex sugars) that are present on the surface of red blood cells and other cells, including cells of the pancreas. The proteins encoded by the A and B forms of the gene transfer different carbohydrates onto the cell surfaces to make A and B blood types. The O form encodes a protein that is unable to transfer carbohydrates. Studies by other researchers have shown that ABO protein encoding in pancreatic tumor cells is different than in normal pancreatic cells.

To discover genetic variations that contribute to pancreatic cancer risk, the research team conducted a genome-wide association study (GWAS).

In a GWAS, researchers analyze common variants, called single-nucleotide polymorphisms (SNPs), in the genomes of people with a disease and people without the disease.

Initially, the research team studied the genomes of 1,896 patients with pancreatic cancer and 1,939 control subjects to identify SNPs with a strong association with pancreatic cancer. The team then verified its findings by studying the genomes of another 2,457 people with pancreatic cancer and 2,654 people without the disease.

In the end, they identified several SNPs on the long arm of chromosome 9 that were associated with pancreatic cancer risk and mapped to the ABO gene.

"Only by working across disciplines and with more than a dozen research groups were we able to make this important discovery of the potential role of the ABO gene in pancreatic cancer risk," said co-author Patricia Hartge, Sc.D., of NCI's Division of Cancer Epidemiology and Genetics (DCEG). "Although it will take much more work, this finding may lead to improved diagnostic and therapeutic interventions that are so desperately needed."