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Is Family History of Breast Cancer a Marker of Susceptibility to Exposures in the Incidence of de Novo Adult Acute Leukemia?¹

Division of Epidemiology and Biostatistics, University of Illinois at Chicago, Chicago, Illinois 60612 [G. H. R.]; National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina [D. P. S., D. S.]; Department of Epidemiology, University of North Carolina at Chapel Hill, North Carolina [C. P., A. F. O.]; Division of Epidemiology, University of Minnesota [J. P.]; and Cancer and Leukemia Group B, The Ohio State University, Columbus, Ohio [C. D. B.]

The risk factors for adult acute leukemia incidence have been difficult to establish.Family history of cancer might interact with environmental exposures to produce associations that are otherwise difficult to detect. In addition to family history of leukemia or other hematopoietic cancers, family history of breast cancer could be a marker of susceptibility, because leukemia and breast cancer are known to cluster in families that have specific germ-line mutations. In a population-based case control study of 779 incident adult acute leukemia patients and 625 controls, we estimated the relative risk for exposed individuals with a family history compared with unexposed individuals without a family history (RR₁₁), along with a measure of interdependence, the interaction contrast ratio. Combined with a family history of breast cancer, ever-smoking [RR₁₁ = 2.4, 95% confidence interval (CI): 1.2–4.8], general solvent exposure (RR₁₁ = 1.9, 95% CI: 1.1–3.4), aromatic hydrocarbon exposure (RR₁₁ = 3.8, 95% CI: 1.1–14), and diagnostic ionizing radiation exposure (RR₁₁ = 2.1, 95% CI: 1.2–3.8) were all associated with increased incidence. Furthermore, there was no increased incidence associated with any of these exposures in the absence of a family history of breast cancer and no increased incidence for family history of breast cancer in the absence of exposures. The pattern of relative risks strongly suggested synergy across exposures. Family history of breast cancer might be a marker of susceptibility to a range of leukemia risk factors, whose effects are generally weak or nonexistent when considered alone.

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