Family history, genetics play growing role in leukemia screening


Inherited susceptibilities to leukemias are becoming better understood and have important implications for screening, prevention, genetic counseling, and treatment.

Timely diagnosis of inherited leukemia-susceptibility genes can improve care or trigger surveillance and prevention efforts, researchers noted at the 58th American Society of Hematology (ASH) Annual Meeting in San Diego.

Following up with genetic counseling and detailed family histories can also lead to screening for relatives.

“We know that susceptibility to leukemia is associated with a wide array of genetic syndromes,” said Kim E. Nichols, MD, of St. Jude Children's Research Hospital in Memphis, Tennessee, during the December 5 session on leukemia genetics. Classic examples are Down syndrome, Noonan syndrome, and Fanconi anemia, where genomic aberrations cause both developmental and cognitive issues, and increase leukemia risk.

But in addition to long-recognized syndromes caused by major “dominant” mutations that can cause cancer alone, researchers are now beginning to recognize another subset of leukemias that are caused by interactions among subtler gene alterations, Nichols said.

Genetic counseling as the ‘standard of care’

“The spectrum of cancer predisposition is increasing and genetic testing is becoming the standard of care,” she said. “Recognition can improve outcomes by facilitating education, treatment modifications, surveillance, prevention measures, and family planning.”

For example, when treating cancers associated with Fanconi syndrome or hereditary retinoblastoma, it’s important to avoid radiotherapy, Nichols noted. Similarly, chemotherapy regimens might be adjusted or organ sparing surgeries indicated.

In addition to gene mutations, epigenetic aberrations-non-DNA-encoded chemical changes to genes-and mutations in regions of the genome that do not encode proteins (and therefore long dismissed as “junk” DNA) also appear to play a role in leukemia risk, she added.


There are several emerging leukemia-predisposition syndromes under study, said Christopher C. Porter, MD, of the University of Colorado School of Medicine, Children's Hospital Colorado, in Aurora, Colorado. One example is an ACD gene mutation that affect chromosomes’ telomeres and hence mutant blood cells’ ability to become “immortal,” dividing without limit.

Syndrome-associated leukemia risk genes or genomic aberrations are often associated with other physical markers of developmental problems, such as unusual facial, limb, or finger morphology.

Nonsyndromic leukemia predispositions can occur when a single gene mutation with weak penetrance increases leukemia risk without causing developmental problems in other organs.


Next: Role of family histories


Role of family histories

Family histories are key in identifying heritable cancer syndromes. Three generation pedigrees are obtained, with an eye toward identifying two or more close relatives with cancer history, and histories of early onset cancers or cancers with multiple primary tumor sites, Nichols noted.

But collecting family histories can be challenging for physicians, who lack time and are rarely trained in how to conduct multigenerational family histories, said Joshua Schiffman, MD, of the University of Utah in Salt Lake City, Utah.

“Patients are also frequently unprepared,” he was quick to add. “Patients and their families may be much less accurate in describing hematological cancers like leukemia than other more common cancers.”

For example, studies show that patients report relatives’ breast cancers approximately 72% of the time, compared to 38% for hematologic malignancies, Schiffman said. His team is developing online tools that would use social network connections to query multiple family members about cancer histories.

When family histories are sought in the context of a patient learning that they have cancer or a genetic predisposition for cancer, the patient might also simply feel too emotionally overwhelmed to help. In such cases, policies and procedures should be in place to encourage clinicians to ask the patient and her family members to gather this information at home for discussion at the subsequent clinic visit.

Access to online tools, like the U.S. Surgeon General’s “My Family Health Portrait,” can help, Schiffman said.

Genetic counseling

Genetic counselors are invaluable at helping patients understand genetic susceptibilities to cancer, he said.

“They can help collect and interpret family histories, and help families make informed decisions about genetic testing,” he said. “They can coordinate testing and help patients interpret results, and help facilitate testing for family members.”

Genetic counselors can also help plan screening and surveillance against cancers for patients who carry susceptibility genes.

Surveillance efforts are intended to detect cancers early in their development, when they can be easier to treat, improving patient survival and reducing impacts to quality of life. That’s particularly true for solid tumors.


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