Dr Dong Pang told the gathering of international cancer experts that among the mothers of 2,604 children who were diagnosed with a solid tumour when they were younger than 15, there were 95 cases of breast cancer – a third higher than the expected number of 73.5.
The risk of breast cancer increased if the child was diagnosed with cancer at a younger age than the median age of the study (5.7 years) or if the affected child was a boy. There were 51 cases of breast cancer amongst mothers of younger children, while only 34 were expected (an increased risk of one half), and 64 cases of breast cancer amongst the mothers of boys, while only 40.4 were expected (an increased risk of three fifths).
Dr Pang, an epidemiologist with the Cancer Research UK Paediatric and Familial Cancer Research Group at the Royal Manchester Children's Hospital, UK, told the conference that the increased risk of breast cancer among mothers of children with solid tumours might be due to some form of mother-foetal interaction during pregnancy, and that hormones might play a role.
"Our study shows that mothers of children with certain types of tumours are at increased risk of developing breast cancer. The risk is higher in mothers of children who are younger than usual at the time of diagnosis of their tumours, and in mothers of boys with tumours. Also the risk of breast cancer is higher during the early years following the birth of the child who subsequently develops cancer," said Dr Pang.
"We know that germline mutations in certain genes, particularly the tumour suppressor gene, p53*, greatly increase the risk of both breast cancer in young women and certain tumours in children – for example embryonal rhabdomyosarcoma, a tumour of the muscle that is thought to originate before birth. The foetus itself is actively involved in the production and regulation of oestrogen, a hormone that is an established risk factor for breast cancer. We think that a combination of disruption of the normal role of p53 in cell cycle control and hormonal disruption during pregnancy contributes to the development of breast cancer in the mother and cancer in the child."
Dr Pang and his colleague, Professor Jillian Birch, the director of the Group, studied the mothers of 2,604 children younger than 15 with solid tumours who were included on the Manchester Children's Tumour Registry between 1954 and 1996. The types of solid tumours diagnosed in the children included lymphomas (cancer of the lymphatic tissue), brain tumours, retinoblastomas (eye), Wilms' tumours (kidney), hepatoblastomas (liver), sarcomas (bone and muscle), skin tumours and germ cell tumours.
The researchers believe that known tumour suppressor genes and cancer-causing genes such as p53 and hCHK2 (a gene associated with breast cancer) may be responsible, in part, for cancer predisposition, but also that other inherited genes such as oestrogen metabolising and oestrogen-regulating genes may be involved as well.
Dr Pang said he believed this was the first study to show the link between breast cancer in mothers and solid tumours other than sarcoma in children, and that it was the first time such a large and comprehensive set of data had been used to confirm the evidence of mother-foetal interaction that had been suggested by an earlier study of Prof. Birch's in 1990.
The research will help doctors to choose the best time to screen women for breast cancer. Speaking from Manchester, Prof. Birch said: "Women with germline p53 mutations are already eligible for breast screening programmes for high risk individuals. Our research helps to define the periods of highest risk and it may be appropriate to screen more frequently during the high-risk periods. The research may point the way to intervention measures aimed at prevention in the future. Suitable measures may become a possibility for children at high risk, but further research to determine the nature of the risk factors is needed."
Dr Pang said: "It is known that some genes are involved in certain childhood cancers and breast cancer in mothers, but we don't know when and how the process of carcinogenesis is initiated. The present study suggests that a crucial period for the development of both breast cancer in mothers and certain cancers in children is the respective pregnancy. Further research incorporating molecular biological studies will help to clarify this issue."
Prof. Birch concluded: "The extreme situation of breast cancer developing in a young woman a relatively short time after giving birth to a child who subsequently develops cancer may provide a means of learning more about the processes involved in breast cancer development in general."
Abstract no: 728 (Wednesday 24 September, 10.45 hrs CET, Public Health and Costs session)
Note
* TP53 is inter-changeable with p53 for the purposes of this release and the authors' abstract, i.e. a tumour suppressor gene. (Some journals use TP53 (Tumour Protein 53) to denote the gene and p53 to denote its protein product, while others use p53 to denote the gene.)