Isolation and stress identified as contributing to breast cancer risk

Social isolation and related stress could contribute to human breast cancer susceptibility, research from a rat model designed at the University of Chicago to identify environmental mechanisms contributing to cancer risk shows.

The researchers found that isolation and stress result in a 3.3-fold increase in the risk of developing cancer among rats with naturally occurring mammary tumours.

The research establishes, for the first time, that isolation and stress could be a factor in human breast cancer risk, said Martha McClintock, a psychologist at the University of Chicago and an author of a paper in current issue of the Proceedings of the National Academy of Sciences. Researchers at the University have been studying social isolation in the context of breast cancer development after having found that that many women living in high-crime neighbourhoods must deal with a variety of stressors, including social isolation. In particular, African American women have been noted to have an earlier onset of breast cancer, although total incidence is similar to women from other ancestries.

'We need to use these findings to identify potential targets for intervention to reduce cancer and other and its psychological and social risk factors,' said McClintock, the David Lee Shillinglaw Distinguished Service Professor in Psychology and Comparative Human Development at the University. 'In order to do that, we need to look at the problem from a variety of perspectives, including examining the sources of stress in neighbourhoods as well as the biological aspects of cancer development.'

The results of the study are published in a PNAS paper titled, 'Social Isolation Dysregulates Endocrine and Behavioural Stress While Increasing Malignant Burden of Spontaneous Mammary Tumours.' Gretchen Hermes, a former researcher at the University and now a resident in psychiatry at the Yale University School of Medicine, is lead author of the study.

The paper is part of a series of publications by University of Chicago researchers exploring the connection between social isolation and breast cancer biology, and part of an ongoing research program at Chicago where work is being done on cancer by researchers from a wide number of disciplines. That work was enabled by the University's Biopsychological Sciences Building, designed for such interdisciplinary research on behaviour and biology and enhanced when the University received a $10 million grant from the National Institutes of Health to finance its Centre for Interdisciplinary Health Disparities Research and is supported by the University of Chicago Cancer Research Centre.

The study published in PNAS found that isolation led to a higher production of a stress hormone, corticosterone, among rats that were kept alone and subjected to the disturbances of colony life as well as stressful situations, such as the smell of a predator or being briefly constrained. Additionally, the isolated rats took longer to recover from a stressful situation than rats that lived together in small groups.

The study also suggests a causal relationship between social interaction and disease by showing that living alone first causes rats to have higher stress hormones, beginning in young adulthood, become fearful, anxious and vigilant and then prone to malignancy in late-middle age. The study further showed that the stress hormone receptor entered the nucleus of mammary tumour cells in isolated rats, where gene regulation occurs, something that happened less often in the cells of the non-isolated rats.

The researchers further found that rats living in isolation experienced a 135 percent increase in the number of tumours and a more than 8,000 percent increase in their size. The impact of isolation was much larger than the impact another environmental source of tumour formation - the unlimited availability of high-energy food.

In natural situations, oestrogen and progesterone produced from ovaries play a role in the majority of naturally occurring mammary and breast cancers tumours. In the rat study, tumours naturally developed in late middle age, while ovaries were no longer fully functioning, further suggesting the role of isolation and stress hormones in cancer development.