Most carriers of Fanconi anemia genes are not at a higher risk of cancer

Dec 12, 2007

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.

“This suggests that the FANCC gene is a breast cancer susceptibility gene, and that women who carry it should be screened for breast cancer on a regular basis,” Auerbach says. The FANCC gene is the second most common Fanconi anemia gene, accounting for about 15 percent of Fanconi anemia families. Many women may already know they carry a mutated gene because FANCC is part of the routine pre-pregnancy genetic testing panel available for persons of Ashkenazi Jewish descent, she says. Half of all families of this Fanconi subtype (called FA-C) are of Ashkenazi heritage.

“Generally speaking, however, these findings are very good news for many people whose families have been affected by Fanconi anemia, because for many years, the assumption has been that anyone who possesses a single mutated gene associated with the disease is at higher risk of developing cancer,” Auerbach says.

The study examined genes from 784 grandparents and 160 other relatives; there were six breast cancers observed among the 33 grandmothers who had a FANCC gene mutation, compared to the 2.5 breast cancers that would be expected. Two other excess breast cancers were found in other female relatives with a mutant FANCC gene.

In addition to quelling the fears of a number of Fanconi anemia gene carriers, the study also cast doubts on theories by which Fanconi anemia genes produce cancer in people who inherit two copies, she says. All 13 genes had been believed to be related to a cancer-causing pathway involving BRCA1 and BRCA2, genes known to be involved in genetic damage repair (but which, when mutated, are breast susceptibility genes) and which are believed to work with Fanconi anemia genes. But this study suggests that only one of the 10 known FA genes found “upstream” of BRCA2, FANCC, may play a role in cancer development.

Citation: Cancer Research 67(19): 9591–9596 (October 1, 2007)

Source: Rockefeller University

Explore further: New cancer drug target involving lipid chemical messengers

add to favorites email to friend print save as pdf

Related Stories

Wireless sensor transmits tumor pressure

3 hours ago

The interstitial pressure inside a tumor is often remarkably high compared to normal tissues and is thought to impede the delivery of chemotherapeutic agents as well as decrease the effectiveness of radiation ...

A nanosized hydrogen generator

4 hours ago

(Phys.org) —Researchers at the US Department of Energy's (DOE) Argonne National Laboratory have created a small scale "hydrogen generator" that uses light and a two-dimensional graphene platform to boost ...

Tim Cook puts personal touch on iPhone 6 launch

4 hours ago

Apple chief Tim Cook personally kicked off sales of the iPhone 6, joining in "selfies" and shaking hands with customers Friday outside the company's store near his Silicon Valley home.

Kiribati leader visits Arctic on climate mission

4 hours ago

Fearing that his Pacific island nation could be swallowed by a rising ocean, the president of Kiribati says a visit to the melting Arctic has helped him appreciate the scale of the threat.

Green dream: Can UN summit revive climate issue?

4 hours ago

Five years ago, the environment movement was in its heyday as politicians, actors, rock stars and protestors demanded a looming UN summit brake the juggernaut of climate change.

Recommended for you

User comments : 0