Number of siblings and the risk of lymphoma, leukemia, and myeloma by histopathology

Epidemiologic evidence indicates that several markers of exposure to childhood infections are inversely associated with the risk of childhood leukemia and lymphomas. We used the Swedish Family-Cancer Database to assess the effects of number of siblings on the risk of nonHodgkin's (n 7,007) and Hodgkin's lymphomas (n = 3,115), leukemias (n 7,650), and multiple myeloma (n = 1,492) by histopathology. Poisson regression models included terms for age, sex, family history, period, and socioeconomic index. Having four or more siblings compared with none was associated with an excess risk of childhood acute lymphoblastic leukemia [ALL; rate ratio (RR), 2.11; P-trend = 0.001], acute monocytic leukemia (RR, 2.51; P-trend = 0.002), and multiple myeloma (RR, 1.34; P-trend = 0.006). Having three or more older siblings compared with none decreased the risk of acute monocytic leukemia MR, 0.35; P-trend = 0.001) and childhood ALL (RR, 0.69; P-trend = 0.01). The risk of Hodgkin's lymphoma for five or more older siblings compared with none was 0.41 (P-trend = 0.003). Acute myeloid leukemia, chronic lymphocytic leukemia, and other lymphoproliferative malignancies were not associated with number of siblings. In conclusion, we found an excess risk of childhood ALL and acute monocytic leukemia in large families. However, for ALL, acute monocytic leukemia, and Hodgkin's lymphoma, younger siblings were strongly protected compared with older siblings. The remarkable protective effect of number of older siblings on acute monocytic leukemia is a novel finding of potential interest. Possible interpretations of our findings in the context of a putative infectious etiology are discussed.