Scientists at the University of Texas M. D. Anderson Cancer Center have found that abnormal genes that repair mistakes in DNA replication may act as an indicator of the risk of pancreatic cancer.
The researchers said that the defects in these critical DNA repair genes might act alone or in combination with traditional risk factors known to increase an individual's chance of being diagnosed with pancreatic cancer.
Advertisement"We consider DNA repair to be the guardian of the genome. If something is wrong with the guard, the genes are more readily attacked by tobacco carcinogens and other damaging agents," said lead author Donghui Li, Ph.D., professor in the Department of Gastrointestinal Medical Oncology at M. D. Anderson.
Thus, the scientists wanted to identify DNA repair genes that could act as susceptibility markers to predict pancreatic cancer risk.
In a case-control study of 734 patients with pancreatic cancer and 780 healthy individuals, they examined nine variants of seven DNA repair genes, which were: LIG3, LIG4, OGG1, ATM, POLB, RAD54L and RECQL.
They searched for direct effects of the gene variants, also called single nucleotide polymorphisms, on pancreatic cancer risk.
Also, the researchers looked for potential interactions between the gene variants and known risk factors for the disease, including family history of cancer, diabetes, heavy smoking, heavy alcohol consumption and being overweight.
It was found that the risk of developing pancreatic cancer was 77 percent lower among people with the variant form of the LIG3 gene (LIG3 G-39A AA).
One the other hand, those with the variant form of the ATM gene (ATM D1853N AA) were more than twice as likely to develop the disease as those without the genetic variation.
After examining possible interactions between gene variants and known risk factors, no significant interplay was found between the abnormal DNA repair genes and smoking, heavy alcohol consumption or excess body weight.
However, two of the gene variants (ATM D1853N and LIG4 C54T) did interact with diabetes to affect pancreatic cancer risk.
The researchers pointed out that the ultimate goal of their research was to identify high-risk individuals for closer scrutiny and follow up.
"We know that people with diabetes have a higher risk of developing pancreatic cancer, but we don't know who will actually develop the disease and who will not. The same is true for smokers. But we can't do CT scans on every diabetic or every smoker," said Li.
He added: "We need to develop biomarkers that will enable us to do a quick genetic test on a diabetic patient, heavy smoker or someone with a family history of pancreatic cancer," she continued. "We could then do a screening test, identify those with the highest risk, and monitor them more closely."
The knowledge of the role of variant DNA repair genes in the development and prognosis of pancreatic cancer would provide the researchers with more insight into their functional significance.
The findings, published in the latest issue of Clinical Cancer Research, may help promote the development of new therapeutic strategies to target these abnormal genes.