Lifestyle influence/damage P53 gene (tumor suppressor)

16 February 2010

New research sheds light on breast cancer prognosis for poorer women

Researchers from the University of Dundee have established a link between deprivation and the p53 gene that explains why women from poorer backgrounds are less likely to survive breast cancer.

In a paper published in this month’s British Journal of Cancer, the Dundee team identifies - for the first time - that p53 mutation in breast cancer is associated with socio-economic deprivation, and that this helps account for the poorer prognosis for women from deprived communities.

Deprivation has long been known to play a role in the development of a wide range of diseases and to a higher risk of recurrence or death for patients diagnosed with a number of cancers, including breast cancer.

The reasons for survival rates differing between breast cancer sufferers from poorer areas and from more affluent areas - the deprivation gap - has never been fully understood.

Initiating this study, Dr Lee Baker, of the Department of Surgery and Molecular Oncology, suggested examining the p53 gene as a candidate molecular marker that might account for these biological differences.

What the team found was that women from deprived backgrounds were more likely to experience a mutation of p53, and that this linked to higher relapse and mortality rates.

'There are two ways that p53 mutations can come about,' explained Dr Baker. 'One is as a result of genetic predisposition, and the other is as a result of lifestyle.

Smoking, drinking, poor diet etc can lead to p53 mutations and are more common in women from lower socio-economic groups, who are also more likely to experience a recurrence of the disease and to die as a result of breast cancer.'

'This research makes a strong link between p53 and deprivation, and then between p53 mutation and recurrence and death. As a social issue, it shows that if we lift people up the deprivation scale then they will be less likely to have problems with their p53 gene, and go on to develop breast cancer.'

'In terms of science, it shows that successfully creating a treatment for p53 mutation will go a long way down the road to finding a cure for this form of breast cancer.

Deprivation alone doesn’t cause breast cancer, but can affect prognosis when p53 is damaged as a result of lifestyle choices commonly associated with deprivation.'

p53 is a tumor suppressor protein that is involved in preventing cancer. In healthy humans, the p53 protein is continually produced and degraded in the cell but if the gene becomes damaged, or mutates, then tumor suppression is severely reduced.

The survey looked at a total of 246 women who underwent treatment for breast cancer between 1997 and 2001. Examining frozen tissue, tests were carried out to determine p53 mutation status. Using the patients’ postcodes, a deprivation score was attributed to each, and examined against the outcome (full recovery, relapse, death etc).

What the team found was that patients in the lowest socio-economic group were significantly more likely to have a relapse and die compared to those in more affluent categories. They also demonstrated that the worse survival and shorter disease-free interval in breast cancer for the most deprived patients is associated with tumour p53 mutation.

The research combines the skill sets of several different disciplines and is an example of the unique combination of clinical data, statistical data and high quality molecular biology laboratory analyses that Dundee is developing. It also featured collaborative working between the University and Roche Diagnostics, a US-based diagnostic company, who developed for this study a novel technology to determine quickly and reliably p53 mutation in tumours.

Alastair Thompson, professor of Surgical Oncology at the University, explained the significance of the research.

'Although the data will in future need confirmation in additional studies, this paper suggests, for the first time, an underlying biology, based around the p53 gene, explaining why women with breast cancer from the most deprived backgrounds do worst in terms of survival,' he said.

'We would like to explore this further with collaborating colleagues in Europe. Our partners Roche Diagnostics produce a test that allows the detection of p53 mutations and that was particularly useful in this context.'

Professor Thompson expressed gratitude to all those who helped fund the study, including the patients, Breast Cancer Research Scotland and the Tayside Tissue Bank, which provided samples and was established with finance from Cancer Research UK and the Medical Research Council.

Ann's NOTE: It is interesting that there is NO mention of stress. Stress which might consist of worry about feeding oneself, ones' children, rushing to a job, being treated 'badly' on the job, rudeness, etc.

About the British Journal of Cancer (BJC) The BJC is owned by Cancer Research UK. Its mission is to encourage communication of the very best cancer research from laboratories and clinics in all countries. Broad coverage, its editorial independence and consistent high standards have made BJC one of the world's premier general cancer journals.

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