Researchers find genetic precursors of leukaemia in patients treated for non-blood cancers

In a study of nearly 9,000 people treated for solid tumour cancers, researchers found that radiation treatment and tobacco use were linked to higher rates of blood-based DNA mutations that could lead to higher risk for blood cancers like leukaemia.
The study revealed new risk factors for “clonal haematopoiesis,” a medical phenomenon in which genetic mutations are found in the blood cells of patients who do not have an existing blood cancer. Twenty-five percent of the patients in the study had clonal haematopoiesis. Of the subset of patients they actively followed, those with clonal haematopoiesis had a small – 1 percent – but increased, estimated incidence of developing blood cancer later on.
“The presence of clonal haematopoiesis can lead to an increased risk for subsequent blood cancers,” said UNC Lineberger’s Catherine Coombs, MD. “We wouldn’t recommend forgoing treatment that is medically indicated because the risk of a secondary cancer is relatively low, but it is important to closely watch those patients who are high-risk.”
The study analysed genetic changes from 8,810 MSK cancer patients. The researchers found clonal haematopoiesis in 25 percent of patients, with the highest incidence in patients with thyroid cancer, and the lowest in patients with germ cell tumours. Mutations were more common in older people, with the odds of clonal haematopoiesis increasing 6 percent for each decade above age 30. Clonal haematopoiesis was also strongly associated with current or former tobacco use.
“A major risk factor for developing clonal haematopoiesis that can be modified or changed is tobacco use," Coombs said.
They also found a higher frequency of patients with clonal haematopoiesis who had received radiation therapy. Forty-one percent of patients with clonal haematopoiesis received radiation, compared to 35 percent of patients who did not have clonal haematopoiesis, and had received radiation.
Risk for developing a secondary blood cancer was very small in the patient population overall.  Only 19 out of the 5,394 patients the researchers actively followed developed a new blood cancer within 18 months. However, for patients who did get a blood cancer, the risk was higher for patients who had clonal haematopoiesis. One percent of patients with clonal haematopoiesis were estimated to develop a secondary cancer, which was three times higher than the estimated 0.3 percent for patients who developed blood cancer and did not have clonal haematopoiesis.
“This has been borne out by other groups: if you have these clonal haematopoiesis mutations, you have a greater risk for developing hematologic cancer than do patients who don’t have them,” she said.

UNC School of Medicine
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