Elevated breast cancer risk among mothers of a population-based series of 2668 children with cancer

Abstract

Aims:Although a previous study found high risk of breast cancer in mothers of children with soft tissue sarcomas, breast cancer risks in mothers of sufferers of other childhood cancers largely remain unknown. The aetiology is not fully understood. The present study explored this excess by varying type of childhood solid cancer and formulated a hypothesis.Methods:Mothers of 2668 children with solid tumours included in the Manchester Children’s Tumour Registry, 1954–96, were traced and followed up to 31 December 2000 through the UK National Health Service Central Register. Standardized incidence ratio (SIR), p-values and 95% confidence intervals were calculated from age and calendar-year-specific female breast cancer incidence rates for England and Wales.Results:There was a significant excess of breast cancer in mothers overall (SIR=1.3, 95%CI=1.0–1.5) mainly due to mothers of children with rhabdomyosarcoma (RMS) (SIR=2.2, 95%CI=1.0–4.0), skin cancer (SIR=7.9, 95%CI=2.9–17.1) and central nervous system tumours (SIR=1.2, 95%CI=0.9–1.8). Maternal breast cancer risk was associated with late age at birth of the index child, and male sex and young age at diagnosis in the index child. Risk was highest in the ten years, following the birth of the index. The pattern was seen most strongly in mothers of children with embryonal RMS.Conclusion:There are excesses of breast cancer in mothers of children with solid tumours in general and specifically in RMS, skin and central nervous system (CNS). There appears to be a temporal relationship between certain tumours in children and breast cancer in their mothers, suggesting an origin of their respective pregnancy. We propose a mother–foetal interaction mechanism to explain this association.

Familial risk of childhood cancer and tumors in the li‐fraumeni spectrum in the utah population database: Implications for genetic evaluation in pediatric practice

“…1 Prior studies have also noted greater magnitude of risks in relatives of children diagnosed with cancers within the LFS spectrum, suggesting that this syndrome may drive some of the familial clustering. 6 However, Searles Nielsen et al . found little evidence to support a relationship between children with brain tumors and family history of brain or other cancers in an international case–control study.…”

“…2–5 The magnitude of risk may vary by the type of cancer presenting in the child, indicating that some cancers may have a greater genetic contribution. 6 However, because of challenges of collecting and updating FHC, reports of the risk of developing cancer to other relatives in families of pediatric cancer probands are few. Limitations of these investigations include that the analyses are often restricted to first-degree relatives, and most rely on parent-reported family histories.…”