Cancer of the pancreas, which strikes more than 40,000 men and women in the United States each year, is an especially deadly malignancy.   There is no effective screening test for the disease and it is usually not detected until it has spread throughout the body.  The five-year survival rate is only about 5%.

Understanding more about the genetic factors that impact pancreatic cancer has the potential to improve prevention and early detection methods, and open new avenues for treatment.  In 2009 one of the first genomewide association studies of pancreatic cancer showed that a SNP on chromosome 9 was associated with risk of the disease.  This finding was not only one of the first strides into understanding the role of common variation in the disease, but it also added new evidence to the decades-long association between type O blood and lower risk for pancreatic cancer.

Now researchers from the same group have found variations in three other regions of the genome that also affect pancreatic cancer risk.  The results, based on an analysis of 3,851 cases and 3,934 controls of mainly European ancestry, were published online this week in the journal Nature Genetics.

The first of the newly identified genomic regions, located on chromosome 13, has been shown by other researchers to be frequently deleted in a variety of cancers, including pancreatic cancer.  There is also evidence that there might be a gene in this region that affects breast cancer susceptibility.  In the current study, the strongest link to pancreatic cancer was with SNP rs9543325.  Having one copy of the C version of this variant increased the odds of pancreatic cancer by 1.23 times compared to those with two copies of the more common (in Europeans) T version.  Having two copies of a C increased odds of the disease by 1.61 times.

The second region the researchers linked to pancreatic cancer risk was on chromosome 1.  Of several variants with statistically significant associations, the strongest was rs3790844. The less common G version of this variation decreased risk of the disease.  Having one copy of a G was associated with 0.75 times odds of pancreatic cancer, while having two copies was associated with 0.64 times odds.

All of the chromosome 1 variants identified by the researchers are located in and around a gene called NR5A2, which appears to be critical for embryonic development and has links to cell growth and division.  All of these functions make it a strong candidate for a gene that is involved in cancer.

The final genomic region associated with pancreatic cancer in this new study is on chromosome 5.  One SNP, rs401681, showed a significant association with the disease.  One copy of a T at this variation was associated with 1.20 times increased odds of pancreatic cancer.  Having two copies of a T increased the odds by 1.41 times.

(23andMe Complete Edition customers can use the links above to check their data for the SNPs identified in this study.)

Rs401681 is near two genes, CLPTM1L and TERT, which have both been linked to cancer.  Previous research has shown that the more common C version of this variation is associated with increased risk of basal cell carcinoma (a type of skin cancer), as well as lung, bladder, prostate and cervical cancer.  There is also suggestive evidence that the C version of rs401681 is associated with increased risk of endometrial cancer.  On the other hand, the T version of rs401681 that was shown to be associated with increased risk of pancreatic cancer in this study has also been found to be associated with increased odds of cutaneous melanoma (another type of skin cancer), and possibly colorectal cancer.

Another research finding of note is that a SNP very near to rs401681 may be associated with the levels of DNA damage caused by smoking.  This is of particular interest because smoking is one of the major risk factors for pancreatic cancer.

The authors of the current study say that more research will be needed to assess how the newly identified genetic variants can be combined with known risk factors for pancreatic cancer—smoking, obesity, diabetes and family history—to identify people who are at high risk for the disease.  They also suggest that further research into the three genomic regions they identified will help guide studies investigating the biological mechanisms underpinning pancreatic cancer.

Pancreatic cancer has received increased media attention in the last year or so due to several high profile people being affected by the disease.  Actor Patrick Swayze died of pancreatic cancer in September 2009.  Randy Pausch, Carnegie Mellon professor and author of “The Last Lecture,” lost his battle with the disease in 2008. Supreme Court justice Ruth Bader Ginsberg had an early stage pancreatic tumor removed in 2009.

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

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A new genetic study has added more evidence to a decades-old association between blood type and the risk for pancreatic cancer.

Close to 42,500 men and women are expected to be diagnosed with pancreatic cancer in the United States this year.  Because there is no effective screening test for the disease and it is often not detected until it has spread, the five-year survival rate for people with pancreatic cancer is only about 5%. The new results, published online this week in the journal Nature Genetics, represent one of the first associations of a common genetic variant with this deadly disease.

Researchers from Harvard and the National Cancer Institute studied more than 4,300 people with pancreatic cancer and 4,500 controls.  They found that each copy of the C version of rs505922 is associated with 1.2 times increased odds of pancreatic cancer compared to two Ts at this SNP.  The study subjects were mainly of European descent, but this association was essentially the same when the small number of people from other ethnic groups (mainly Asian and African American) was also included in the analysis.

(23andMe customers can check their data for rs505922 using the Browse Raw Data feature.)

The non-risk T version of rs505922 is linked to the variation in the ABO gene that results in type O blood.  People with two Ts are type O.  The riskier C version of the SNP is found in people with type A, B and AB blood.

Epidemiological studies from the 1950s and 1960s, as well as more recent reports, have suggested that people with type O blood are at lower risk for pancreatic cancer compared to those with type A or type B blood.  Finding the association of rs505922 with the disease in a genetic study adds more credence to these previous results. What’s still not understood, however, is why people with type O blood are less likely to get pancreatic cancer.

In their concluding remarks, the authors of the study stressed the need for further research into the genetic risk factors for cancer of the pancreas.

“As there are few known risk factors, improved diagnostics and a finer understanding of the molecular pathogenesis are urgently needed…. The discovery of additional genetic risk variants for this highly lethal cancer could contribute to improvements in … prevention, early detection and therapeutic approaches to pancreatic cancer,” the authors write.

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BRCA1 and BRCA2 (BRCA1/2) mutations account for most (though not all) cases of inherited breast cancer in women. These mutations are also associated with an increased risk for ovarian cancer. In men, BRCA1/2 mutations increase the risk for breast cancer and may also increase prostate cancer risk.  Research has indicated there may also be an increased risk of melanoma and pancreatic cancer in people with BRCA1/2 mutations.

Although BRCA1/2 mutations significantly increase the risk of cancer, having one of these mutations doesn’t mean a person actually has cancer or will necessarily ever get the disease.   But new research from scientists at the National Cancer Institute and the National Human Genome Research Institute, published online this week in the journal PLoS ONE, suggests that those BRCA1/2 carriers who do escape cancer may still be at risk of a shorter than average lifespan.

In a study of almost 5,300 people with Ashkenazi Jewish ancestry researchers found that, on average, both men and women who carry BRCA1/2 mutations die younger — even when cancer deaths are excluded from the analysis.  Among women free of melanoma, breast, ovarian and pancreatic cancer, BRCA1/2 mutation carriers died 5.8 years earlier (age 75.0 vs. 80.5) than those women without the mutations. In men, after excluding cases of melanoma, prostate and pancreatic cancer, BRCA1/2 mutation carriers died about 3.7 years earlier than those without the mutations (71.0 years old vs. 74.7).

“Theoretically, these mutations may either be associated with a small increase in risk of a variety of different diseases, or they may be associated with moderate increase in risk of a few major diseases,” the authors write.  They note that the current study is unable to make this distinction because it did not collect information on non-cancer related causes of death.

The researchers analyzed the effects of only the three BRCA mutations that are most common in Ashkenazi Jewish people: 185delAG in BRCA1, 5382insC in BRCA1, and 6174delT in BRCA2.  The mutations account for 80-90% of hereditary breast and ovarian cancer in this ethnic group.  But there are hundreds of other BRCA1/2 mutations that have been associated with cancer, and the authors caution that further studies taking these other BRCA1/2 mutations into account and using study subjects from diverse groups will be needed to confirm their results.

(23andMe provides data for the three BRCA1/2 mutations most commonly found in people with Ashkenazi Jewish ancestry in the BRCA Cancer Mutations (Selected) Carrier Status Clinical Report.)

The authors conclude that understanding the effects of BRCA1/2 mutations on non-cancer related deaths could eventually help scientists understand how the mutations affect cancer risk and may even facilitate efforts aimed at finding new ways of preventing disease in BRCA1/2 mutation carriers.

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The cells in our bodies are subject to a constant onslaught of potentially damaging chemicals. Some of these come from the environment – the toxins in cigarette smoke, for an example – while others are natural byproducts of cellular life. Regardless of their origin, these chemicals have the potential to cause serious DNA damage that can eventually result in cancer.

Cells have evolved numerous mechanisms for defusing the danger posed by these chemicals. In the event that these efforts fail and DNA damage does occur, cells also have their own DNA repair systems. Not surprisingly, mutations in the genes that encode these DNA-fixers can leave cells vulnerable and increase the chances that a cancer will develop. Bloom’s syndrome, Fanconi anemia and hereditary breast cancers caused by BRCA mutations are all examples of cancer syndromes caused by relatively rare functional mutations in DNA repair genes.

Research from the University of Texas M.D. Anderson Cancer Center in Houston published online today in Clinical Cancer Research shows that common variations, not just rare mutations, in DNA repair genes can increase the risk for pancreatic cancer.

Pancreatic cancer is the fourth leading cause of cancer death for both men and women in the United States. Environmental factors such as smoking, obesity, diabetes, chronic pancreatitis and dietary factors are known to play a part in determining the risk of pancreatic cancer, but about 10% of patients have a family history of the disease, suggesting that there are also genetic risk factors.

Donghui Lie and colleagues examined variations in several DNA repair genes among 734 non-Hispanic white pancreatic cancer patients and 780 people without the disease. They found that having two copies of the A version of rs1801516 in the ATM gene increased the odds of pancreatic cancer 2.76 times compared to two Gs. Having just one copy of the A version did not significantly increase risk.

(23andMe customers can check their data using the Browse Raw Data feature.)

SNPs in the ATM gene have also been associated with an increased risk of developing breast cancer. The protein encoded by ATM is known to be crucial for the cellular response to DNA damage.

The researchers also found a significant association between having two copies of the A version of rs2074522 in the LIG3 gene (also involved in DNA repair) and risk for pancreatic cancer. 23andMe does not currently provide data on this SNP.

“Pancreatic cancer is a highly fatal disease because most of the cases are diagnosed at late stage and the tumors are resistant to most therapies. Early detection for pancreatic cancer is crucial to reduce the mortality,” the authors write.

“However, there is no screening method available to identify the high-risk individuals among those at risk,” they write — referring to people such as smokers, people with diabetes, and those with a family history of pancreatic cancer.

The authors suggest that in addition to aiding in the development of screening tests for pancreatic cancer, finding and understanding variants such as those identified in their study will help aid in developing new treatments.

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