Cancer in the families of children with soft tissue sarcoma

Abstract

The cancer experience among 754 first-degree relatives (mothers, fathers, and siblings) of a population-based series of 177 children with soft tissue sarcoma is reported. The current study represents an extension of our earlier work in which the authors found an excess of breast cancer in the mothers of 143 of these children. There were 40 cancers among all first-degree relatives, compared with 24.82 expected (relative risk [RR] 1.61, P = 0.006). There was no excess in fathers, but an excess of borderline significance was seen in mothers (RR 1.67, P = 0.0545), and a significant excess in siblings (RR 4.55, P = 0.0002), mainly due to carcinoma of the breast and pediatric tumors. Results of a step forward Cox multivariate analysis identified three variables in the index child which were independently associated with high cancer risk in relatives, as follows: age younger than 24 months at diagnosis; histologic type, embryonal rhabdomyosarcoma or other and unspecified soft tissue sarcoma; and male sex. It was possible, therefore, to identify a subgroup of children whose relatives are at high risk of early onset cancer (RR in this group 10.14). The pattern of cancers is consistent with the Li-Fraumeni syndrome. The authors conclude that a marked proportion of childhood soft tissue sarcoma has a genetic basis.

Li-Fraumeni syndrome – a molecular and clinical review

“…However, preliminary data do exist that could provide some guidance. On the basis of population studies of cancer risks in families of children with sarcoma and follow-up studies in families with LFS, it has been shown that the risk of cancer is elevated up to, but not beyond, age 60 years (Birch et al, 1990;Garber et al, 1991). Using a data set comprising details of occurrence of cancer among the close relatives of a hospital-based series of children who had survived sarcoma, Lustbader et al (1992) conducted a segregation analysis.…”

Cooperation of oncogenic K-ras and p53 deficiency in pleomorphic rhabdomyosarcoma development in adult mice

“…Mutations in p53 have also been found in nearly 50% of RMS cases and cell lines (Mulligan et al, 1990;Felix et al, 1992;Merlino and Helman, 1999). Furthermore, association with a p53 germline mutation has been reported in a childhood RMS case (Birch et al, 1990) and in families predisposed to this malignancy (Malkin et al, 1990).…”

Cancer experience in the relatives of an unselected series of breast cancer patients

“…There is an established excess risk of breast cancer for the mothers of children with a sarcoma (Li et al, 1969;Birch et al, 1984Birch et al, , 1990Strong et al, 1987). Buirki et al (1987) found an excess of sarcomas in the brothers of breast cancer patients.…”