Several risk factors have been identified, but they do not account for all cases of chronic leukemia. Environmental factors such as exposure to high-dose radiation may increase the risk of CML. In more than 90% of patients with CML, there is the presence of the abnormal Philadelphia (Ph1) chromosome, which may be induced by radiation or carcinogenic chemicals. Long-term contact with herbicides and pesticides may increase the risk of CLL. Heredity is a factor: members of the immediate family (parents, siblings, children) who have had CLL create an inherited risk factor. Finally, smoking has been shown to increase the risk of leukemia.

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