title: Cancer incidence in persons with Fanconi anemia.
abstract: Fanconi anemia (FA) is an autosomal recessive condition associated with congenital abnormalities, progressive pancytopenia, and a predisposition to leukemia and solid tumors. We studied a retrospective cohort of North American patients with FA. We calculated relative risks of cancer compared to the general population and cause-specific hazards of the first major adverse outcomes of FA: bone marrow transplantation (BMT) for marrow complications, acute myeloid leukemia (AML), solid tumors, or death from bone marrow failure. We also estimated the cumulative incidence of each adverse event in the presence of the competing risks. Among 145 patients with FA, 9 developed leukemia and 14 developed a total of 18 solid tumors. The ratio of observed to expected cancers (O/E ratio) was 50 for all cancers, 48 for all solid tumors, and 785 for leukemia; these increased risks were statistically significant. The highest solid tumor O/E ratios were 4317 for vulvar cancer, 2362 for esophageal cancer, and 706 for head and neck cancer. Cause-specific hazards of both death and AML peaked at 1%/y in teenage years; the hazard of BMT peaked at 4%/y at age 7. In contrast, the hazard of a solid tumor approached 8%/y by age 40 years. The cumulative incidence to age 48 was 10% for leukemia, 11% for death from marrow failure, 29% for a solid tumor, and 43% for BMT. The risk of a solid tumor may become even higher as death from aplastic anemia is reduced and as patients survive longer after BMT.
authors.affiliation: Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Rosenberg
authors.forename: Mark H
authors.initials: MH
authors.lastname: Greene
authors.forename: Blanche P
authors.initials: BP
authors.lastname: Alter
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D016026:Bone Marrow Transplantation / Q000706:statistics & numerical data; D015984:Causality; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005199:Fanconi Anemia / Q000150:complications* / Q000453:epidemiology / Q000401:mortality; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007951:Leukemia, Myeloid / Q000453:epidemiology / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000453:epidemiology / Q000209:etiology; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012306:Risk