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Last Updated: Monday, 30 May, 2005, 23:20 GMT 00:20 UK
Infancy 'determines cancer risk'
Breast cancer cells
Some breast cancers depend on oestrogen to fuel their growth
The earliest days of life could determine if risky genes will go on to trigger cancer, scientists claim.

Genes such as BRCA1 and BRCA2 for breast cancer significantly increase the risk of developing the disease, but not all carriers develop tumours.

A University of Texas study on rats suggested exposure to the hormone oestrogen just after birth could determine if tumours will develop.

The research is in the Proceedings of the National Academy of Sciences.

'Hypersensitivity'

It suggests exposure to oestrogen may reprogramme tissue and set it on a path towards the eventual development of disease.

The researchers studied female rats which were genetically predisposed to develop uterine leiomyoma, the same kind of benign fibroid tumours that many women have.

For gene-environmental interactions, the timing of the exposure may be critical, and it may happen much earlier than anyone ever suspected
Professor Cheryl Walker, University of Texas
Typically, around 65% of rats with this defect go on to develop these tumours.

Some of the animals studied were exposed to DES (diethylstilbestrol), a drug once used to prevent miscarriage, three to five days after they were born - a crucial period in the development of their reproductive tract - while others were not.

DES is oestrogenic, which means it works on the body in the same way as natural oestrogen hormones.

A third group of rats, which had already developed the cancer without exposure to DES were also studied as a comparison to the other animals.

The researchers found that by the time rats exposed to DES had reached adulthood (16 months of age) virtually all of them had developed leiomyoma.

The tumours were larger and more numerous than in rats who had developed the tumours naturally.

In contrast, none of the DES-exposed rats that lacked the genetic defect developed tumours by 16 months.

Critical timing

The team suggests the DNA of DES-exposed animals had been modified in a way that changed how genes responded to oestrogen, causing them to be hypersensitive to the effects of the hormone.

The researchers say this provides the first evidence that exposure to oestrogen early in development can "reprogramme" tissue in a way which determines whether or not tumours will develop in adulthood.

The team, led by Professor Cheryl Walker, said its findings were likely to be relevant for people who inherited defective tumour suppressor genes that made them susceptible to a number of different cancers.

They said it could, for example, explain why some women who inherited BRCA1/2 gene defects developed breast cancer as adults while other women with the same genes remained disease-free.

Professor Walker said: "The kind of developmental reprogramming we see from this work could represent an important determinate of risk in people genetically susceptible to hormone-dependent tumours, such as uterine, breast and prostate cancer.

The team says more work is needed to support the theory human cancer risk is affected in the same way.

But Professor Walker added: "This study suggests that for gene-environmental interactions, the timing of the exposure may be critical, and it may happen much earlier than anyone ever suspected."


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