For almost 50 years, Fanconi anemia has been associated with leukemia. Not just among those who have the genetic disorder but among their family members, whose genes, they were told, made them highly susceptible to a variety of malignancies.
But a new study to examine links between 13 specific Fanconi anemia genes and cancer risk has determined that in most cases, their risk of cancer is no greater than that of the rest of the population.
Fanconi anemia is primarily an autosomal recessive genetic condition, which means that in order for it to develop, a person must inherit two mutated Fanconi anemia genes, one from each parent. To date, 13 such genes have been identified and all of them, in Fanconi anemia patients, are associated with a greater than average risk of developing solid as well as blood-based cancers, among other conditions.
The question that Rockefeller University Associate Professor Arleen Auerbach and her team of American and German researchers investigated is one she says has worried families of Fanconi anemia patients for decades: whether a single Fanconi anemia gene increases cancer risk. A pivotal 1971 epidemiological study suggested that cancer risk is, indeed, elevated in Fanconi carriers, although no molecular genetic analysis was performed, Auerbach says. When a 2002 study linked Fanconi anemia to the BRCA2 gene, researchers suggested that inherited mutations in any of several genes might result in cancer risks for Fanconi anemia. ?This produced a kind of mass hysteria among family members because they believed carriers were all at increased risk for cancer in general and breast cancer in particular,? Auerbach says.
But the new data, which Auerbach and her colleagues spent six years collecting and analyzing, suggests that besides those with BRCA2 mutations, only one subgroup of Fanconi anemia carriers ? older women who carry a single mutated FANCC gene ? develop more than the expected amount of cancer. Investigators further found that the cancer these women developed was of one type ? breast cancer. In this study, grandmothers of Fanconi anemia patients who carry an FANCC gene were almost 2.5 times more likely to have developed breast cancer compared to women without the gene, says Auerbach, director of the Laboratory of Human Genetics and Hematology and the study?s lead investigator.