There is some bad news for those carrying genes that can lead to Fanconi anemia, a rare blood disorder.
Recently, a team of scientists at Johns Hopkins Kimmel Cancer Center found that three genes linked to Fanconi anemia play a role in pancreatic cancer, one of the most lethal forms of the malignancy.
The study, directed by Dr. Scott Kern, identified the genes as “a new genetic cause of some cases of pancreatic cancers.” Those who carry any one of the genes have a greatly increased risk of pancreatic cancer.
“It’s clear that a mutation raises the risk [of cancer] on the order of 10 to 20 fold,” Kern said in an interview with the Forward.
However, Kern says, there’s a bit of good news among the bad: The gene mutations, bad as they are, may make the cancer they cause more responsive to treatment with certain drugs.
Fanconi anemia, or FA, is a rare disorder caused by the hereditary loss of both copies of certain genes. According to the Kimmel Center, the disease affects fewer than one in 100,000 people. One in 80 Jews of Ashkenazic descent are carriers of genes causing FA, according to Familypracticenotebook.com. Children afflicted with the disease must inherit the mutation from both parents.
Those afflicted with FA are often born with various congenital defects. “They could have an absence of certain bones, or a thumb. Or their stature could be abnormal,” Kern said. “After a period of years, most Fanconi patients develop an anemia or a deficiency in one or more of the lines in the blood cells.” Without a bone marrow transplant, he added, the disease is usually fatal.
The three genes the researchers identified normally function as part of the DNA repair process. Previous studies linked one of the genes Kern and his team pinpointed, BRCA2, to breast cancer.
Kern said that a mutation on both sides of this gene and mutations on two other genes, FANCC and FANCG, should cause malignant pancreatic cells to be susceptible to treatment with two drugs, mitomycin C and cisplatin, both of which are approved by the Food and Drug Administration.
“People have… done these studies… and have shown that the mouse cells and hamster cells have been susceptible,” he said. He also cited preliminary trials that have yielded positive results.
Kern said that clinical trials are likely to begin within the year and will have to be designed to “take into account the new theories of Fanconi genes.”
“We have lots of loose ends, lots of work to be done in the future,” he said. “But I think people will figure out this relationship.”
He added that the discovery process is slow “in part because testing is expensive, in part because some people are afraid of genetic testing, and in part due to federal regulations.”
Kern mentioned that if people with FA live long enough, they tend to get cancer at about age 29.
“Most people haven’t studied FA genes as being tumor related,” he said. “But these are people who already have a DNA repair defect in their whole body, so it’s not surprising that they have cancer.”
Those with only one copy of the mutated gene — that is, people who are carriers of the disease gene, but are not afflicted with the disease itself — also should worry.
“If you inherit one bad copy and it stays as one bad copy, you would presumably have much less risk for cancer,” Kern said. “But as humans age, they very often lose additional copies.”
At the same time, however, if a person does develop an additional mutated gene later in life because of diet or environmental factors, Kern thinks that drugs like mitomycin C could be helpful to them, too.
“Nobody has tested that yet, but we all see that as the obvious thing to do,” he said. “We are talking with a number of people on how it can be done.”
Mitomycin C has been used to treat many different types of cancers, often with unpredictable results, Kern said. But Kern thinks it is likely that “the people who responded were the ones with the FA genes that got mutated.”
In the study, the Johns Hopkins-based research team contrasted the genome from pancreatic DNA to that of normal DNA. “Normal cells have genes in them that help to regulate them,” Kern said. “One of their functions is to prevent cancer.”
The researchers looked to find tumor suppressor regions that were no longer there and had thus caused the cells to behave like cancer. The doctors found that there are seven different FA genes and that the symptoms look the same irrespective of which gene causes the disease. The team was able to elucidate the specificities of three of the genes.
Kern said that the other four are variants of the three in which the sequence of the gene is slightly altered. He does not yet know what those differences might mean.
“For the scientists, that’s great because it gives us something to study for a few years,” he said. “But for patients, it’s not, because it will take some years for us to figure things out.”