No Increased Acute Myeloid Leukemia Risk in First-Degree Relatives



LONDON – Close relatives of patients with acute myeloid leukemia and myelodysplastic syndromes can be reassured that they are not at increased risk of developing these diseases themselves, according to the findings of a large population-based registry trial.

"Among over 20,000 first-degree relatives of almost 7,000 AML [acute myeloid leukemia] patients, we found no excess risk of developing AML, MDS [myelodysplastic syndromes], or any myeloid neoplasms as a group," said Dr. Magnus Björkholm, a professor of medicine at Karolinska University Hospital, Solna and the Karolinska Institute, both in Stockholm.

Speaking at the annual congress of the European Hematology Association, Dr. Björkholm reported that there was also no strong genetic predisposition for first-degree relatives of patients with MDS to develop myeloid or other hematological neoplasms.

"If you read Wikipedia today, it says that the risk of developing AML is increased threefold in first-degree relatives of patients with AML," Dr. Björkholm observed. "But there is really limited data on the extent of familial aggregation of AML and MDS in the population.

Indeed, the Wikipedia entry cites a paper (J. Natl. Cancer Inst. 1969;42:517-24) from 1969 as the source of this claim, and results of early studies found an increased risk of leukemia among relatives of patients were actually accounted for by cases of chronic lymphocytic leukemia.

"We believe a better understanding on the role for genetic factors in the causation of AML/MDS is of major importance to patients, their families, and healthcare professionals," Dr. Björkholm said, explaining the rationale behind the research.

Using data from the Swedish Cancer Registry, the Swedish Population Registry, and the Swedish Multigenerational Registry, Dr. Björkholm and colleagues identified 6,962 patients diagnosed with AML from Jan. 1, 1958 until Dec. 31, 2004 and 1,388 MDS patients diagnosed from 1993 – the date when MDS was first included in the Swedish Cancer Registry – through Dec. 31, 2004. There were 20,579 first-degree relatives of the AML patients and 3,994 first-degree relatives of the MDS patients.

For each AML and MDS patient, four population-matched control subjects of a similar age, year of birth, and country of residence were randomly selected from the Swedish population, and their first-degree relatives were also identified. In all, there were 27,827 AML controls and 90,406 AML control relatives, and 5,312 MDS controls and 15,818 MDS control relatives.

No excess risk of AML (hazard ratio 0.94) or other myeloid or lymphoid malignancies was statistically significant in relatives of patients with AML with one exception – relatives of patients with AML did have an increased risk of polycythemia vera (HR 2.28, P less than .05). The risks for any hematopoietic or solid malignancies were significantly increased statistically, but only modestly, with risk ratios of 1.16 and 1.09, respectively.

First-degree relatives of AML patients who were diagnosed at a younger age (20 years or less) did, however, have a higher chance of developing AML, myeloid neoplasms, or multiple myeloma, based on small numbers in the sample. Dr. Björkholm suggested that genes predisposing to malignancy in general, environmental factors, or both, might be shared in these families.

No significant excess risks were seen among first-degree relatives of MDS patients.

"The lack of familial aggregation in AML and MDS is rather striking," Dr. Björkholm admitted. It is also "in stark contrast to findings in other myelo- and lymphoproliferative disorders."

In an interview, he emphasized, "The main message is that first-degree relatives of patients with acute myeloid leukemia do not have an increased risk of developing acute myeloid leukemia, which is in contrast to many other solid and hematological malignancies."

Dr. Björkholm also noted that patients are often told by their physicians that there is a two to three times increased risk of their siblings or children developing leukemia. The current findings suggest that this is unlikely, considering the large cohort of subjects that was studied.

"From a global point of view, this [study] is probably the best you can do."

Dr. Björkholm stated he had no conflicts of interest. The study received financial support from the Adolf H. Lundin Charitable Foundation, Karolinska Institute Foundations, Stockholm County Council, Swedish Cancer Society, and the Division of Intramural Research Programs at the National Cancer Institute of the National Institutes of Health.

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