RADIATION AND GENETIC-FACTORS IN THE RISK OF 2ND MALIGNANT NEOPLASMS AFTER A FIRST CANCER IN CHILDHOOD

Background Radiotherapy and chemotherapy are associated with an increa sed risk of second malignant neoplasm (SMN). An association between SM N and familial aggregation has also been shown. The aim of this study was to investigate the role of familial factors in the risk of SMM and their potential interaction with the effect of treatment. Methods We devised a case-control study of 25 children with SMN (cases) and 96 ch ildren with no SMN after a cancer treatment (controls), taken from a c ohort of 649 children treated at our institution between 1953 and 1985 . A complete family history was obtained for patients and controls and a familial index defined to evaluate the degree of familial aggregati on. The radiation dose given at 151 sites in the body was estimated fo r each radiotherapy course for each child. Findings Among family membe rs of the 25 SMN cases, there were ten with early-onset (less than or equal to 45 years) cancer, compared with eight among relatives of the 96 controls. Compared with patients who had no family history of early -onset cancer, those with one or more affected family members had an o dds ratio of SMN of 4.7 (95% Cl 1.3-17.1; p=0.02). Adjustment for loca l radiation dose and exclusion of patients known to be predisposed to SMN (carriers of p53 mutation and those with Recklinghausen's disease) did not affect this risk substantially. Interpretation Both genetic f actors and exposure to ionising radiation have independent effects on the risk of SMN. Follow-up of children treated for cancer should be es pecially vigilant when there is a family history of early-onset cancer .