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Understanding breast cancer risk in Chinese populations

Obesity has long been associated with an increased risk of breast cancer in post-menopausal women. But the relationship between obesity and breast cancer is less clear in pre-menopausal women. Moreover, a lot of uncertainty remains around the associations between body weight and breast cancer in countries such as China, where the average BMI is lower than in western countries, along with differences in the prevalence of other risk factors between western and eastern cultures. There is a need to better understand how morphological and lifestyle differences between populations may influence cancer incidence, in order to better understand and identify who is at an increased risk.

An upcoming study from the Clinical Trial Service & Epidemiological Studies Unit (CTSU) at the Nuffield Department of Population Health, led by Dr Christiana Kartsonaki and Dr Ling Yang, is investigating breast cancer incidence in Chinese populations in relation to adiposity measures such as BMI, waist circumference and body fat percentage.

The team used data from the China Kadoorie Biobank, a cohort study that has collected information from over half a million individuals from China since 2004. During an average of 10 years of follow-up of this cohort, there were 2,053 cases of breast cancer, which allows the team to assess what demographic or lifestyle factors might be influencing risk in Chinese women.

Early results suggest that, like western populations, increased levels of adipose tissue leading to higher BMIs are associated with higher risks of breast cancer in Chinese women, particularly among post-menopausal women. These results highlight the importance of understanding relative cancer risk factors between different ethnicities. Whilst some factors such as obesity are often common causes of cancer across all populations, there are many key biological and lifestyle factors that differ between western and eastern populations. Understanding how these may impact cancer risk in different ways will allow researchers to inform policy, so that clinicians may better identify who may have a higher risk of developing cancer.

About the CTSU

The Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU) aims to generate and disseminate reliable evidence from observational epidemiology and from randomised trials that leads to practicable methods of avoiding premature death and disability.

This project is being led by Dr Christiana Kartsonaki and Dr Ling Yang in conjunction with Prof. Zhengming Chen.

Using big data in breast cancer research

Breast cancer is the most common type of cancer found in the UK population, with 1 in 8 women diagnosed during their lifetime. As a prevalent cancer, it’s important to understand more about the potential causes and relative risks that individuals from different demographics might have.

The Cancer Epidemiology Unit (CEU) at the Nuffield Department of Population Health specialises in large-scale studies into the lifestyle and genetic risk factors of cancers such as breast cancer. In doing so, these studies can provide evidence to inform public health policies and answer outstanding questions about how cancers may arise.

The cause of breast cancer has long been researched and over the last two decades, findings from the Unit’s large prospective studies and international collaborations have helped clarify the role of many risk factors for the disease, including use of menopausal hormones and oral contraceptives, as well as factors relating to childbearing. Within the last year, an updated review of the worldwide evidence carried out in CEU showed that menopausal hormone usage increases the long term risk of breast cancer by almost twice as much as was previously thought, findings which influenced public health guidance. Other recent work found evidence to suggest that high fruit and fibre intake and physical activity may be associated with lower risks of breast cancer.

The CEU work with big data, such as its Million Women Study which contains data from 1.3 million UK women, collected since it began  in 1996. The study includes 1 in 4 of all UK women born between 1935 and 1950 and remains the largest data set of its kind. The study, which aims to resurvey women every 3-5 years, continues to collect information on new potential risk factors such as working night-shifts (which in this case was shown to have no influence on breast cancer incidence).

Enhancing the quality and quantity of the Million Women Study dataset is high on the CEU’s agenda. One area of research where the study hopes to be able to contribute substantially over the next few years is in risk stratification for breast cancer. Prediction models which can be used to assess an individual’s breast cancer risk are key for planning risk-based screening approaches that are tailored to an individual, so refining their accuracy is important to ensure that interventions can be targeted appropriately. However, while existing risk prediction models look promising they need further improvement in their ability to identify those women who are most likely to get breast cancer before they can be applied at a population level. In particular, models should ideally incorporate the whole spectrum of breast cancer risk factors including genetic variation and radiological imaging data.

This will be the next stage for the Million Women Study, as Prof Gill Reeves, Head of the CEU, hopes to integrate new datasets into the study. This includes digital screening images from mammograms, and other clinical information, which could be used in combination with existing information held on participants, to allow the CEU to develop more accurate risk prediction models from the Million Women’s Study.

Prof Gill Reeves, Head of the CEU, says:

“Enriching the quality of datasets such as the Million Women Study will allow us to continue to provide reliable evidence regarding the effects of behavioural and biological factors on breast cancer risk, and help identify women who are at particularly high risk of the disease. In doing so, we can better inform public health advice, and clinical practice.”

To read more about the CEU’s work on breast cancer go to the  CEU website.

About the CEU

The CEU runs the Million Women’s Study (MWS) and EPIC-Oxford (two large cohort studies). Recent grant funding from CRUK has allowed for further enhancement of the MWS so that new clinical data and other potential risk factors for cancer may be integrated.

Prof Gill Reeves, Head of the CEU, is a Professor of Statistical Epidemiology. Her main research interests are the roles of hormonal and other risk factors in the development of female cancers.  She is particularly interested in risk factors and patterns of survival for molecular subtypes of breast cancer.

 

Men with high oestrogren levels could be at greater risk of breast cancer

Men with naturally high levels of the female hormone oestrogen may have a greater risk of developing breast cancer, according to research by an international collaboration including Cancer Research UK published in the Journal of Clinical Oncology.

This is the first time a link between oestrogen levels in the blood and male breast cancer has been identified, despite its connection to breast, womb and ovarian cancers in women.

Men with the highest levels of oestrogen were two and a half times more likely to develop breast cancer than men with the lowest levels of the hormone. Low levels were classified as less than 52.23 picomols of oestrogen per litre of blood (pmol/L), and high levels were more than 86.76pmol/L.

Male breast cancer is very rare with one man in every 100,000 diagnosed with breast cancer each year in the UK. Around 350 male cases are diagnosed each year in the UK compared with nearly 50,000 cases of breast cancer in women.

The research at the National Cancer Institute in the United States was part of an international collaboration between Cancer Research UK, the National Cancer Institute and many other vital funders.

The aim was to study a large international pool of men with breast cancer. The research compared oestrogen levels in 101 men who went on to develop breast cancer with 217 healthy men.

Mark Cross, 46, a police officer from Cambridgeshire, was diagnosed with breast cancer in 2009. He had a mastectomy and then follow-up treatment of chemotherapy and radiotherapy. His treatment ended in September 2010. He said: “The police sometimes get a bit of a reputation for being macho but I had great support from everyone within the Metropolitan police service. Not many people know that men get breast cancer too and it was a complete surprise to be diagnosed. My advice to all men is if you develop a lump on your chest – or anywhere else on your body – get it checked by your doctor as soon as possible. I hope my experience will raise awareness for other men.”

Study author Professor Tim Key, Cancer Research UK’s hormone and nutrition expert at the University of Oxford, said: “We’ve shown for the first time that just like some forms of the cancer in women, oestrogen has a big role to play in male breast cancer. So now the challenge is to find out exactly what this hormone is doing to trigger this rare form of the disease in men, and why some men have higher levels of oestrogen in their blood. Our discovery is a crucial step forward in understanding the factors behind male breast cancer.”

The symptoms, diagnosis and treatment of male breast cancer are very similar to breast cancer in women. The main risk of developing the disease in men is age and almost eight in 10 cases are diagnosed in those aged 60 and older.

Dr Julie Sharp, head of health information at Cancer Research UK, said: “Breast cancer in men isn’t discussed very often, so a diagnosis can be a big shock for the small group of men who develop the disease.

“Some of the oestrogen variation in men will simply be natural, but for others there may be a link to being overweight. Fat cells in the body are thought to drive up the body’s level of this hormone in men and women, so this is another good reason to try and keep a healthy weight.

“This early research is crucial in understanding why these men get breast cancer – so that one day we can treat it more effectively.”

Metal test could help diagnose breast cancer early

A team, led by Oxford University scientists, took techniques normally used to analyse trace metal isotopes for studying climate change and planetary formation and applied them to how the human body processes metals.

In a world-first the researchers were able to show that changes in the isotopic composition of zinc, which can be detected in a person’s breast tissue, could make it possible to identify a ‘biomarker’ (a measurable indicator) of early breast cancer.

A report of the research by the Oxford University-led team, which included researchers from Imperial College London and the Natural History Museum, London, is published in the Royal Society of Chemistry journal Metallomics.

The pilot study analysed zinc in the blood and blood serum of ten subjects (five breast cancer patients and five healthy controls) alongside a range of breast tissue samples from breast cancer patients. By using techniques that are over 100 times more sensitive to changes in the isotopic composition of metals than anything currently used by clinicians, the researchers were able to show that they could detect key differences in zinc caused when cancer subtly alters the way that cells process the metal. Similar changes in copper in one of the breast cancer patients is additional evidence that it may be possible to identify a biomarker for early breast cancer that could form the basis of a simple, non-invasive, diagnostic blood test.

‘It has been known for over a decade that breast cancer tissues contain high concentrations of zinc but the exact molecular mechanisms that might cause this have remained a mystery,’ said Dr Fiona Larner of Oxford University’s Department of Earth Sciences & CRUK Oxford Centre Member, who led the research. ‘Our work shows that techniques commonly used in earth sciences can help us to understand not only how zinc is used by tumour cells but also how breast cancer can lead to changes in zinc in an individual’s blood – holding out the promise of an easily-detectable biomarker of early breast cancer.’

The researchers say that this new understanding of cancer cell behaviour – in particular the role sulfur-containing proteins play in how tumours process zinc – could also help in the development of new cancer treatments.

‘The hope is that this research is the beginning of a whole new approach,’ said Dr Larner. ‘Understanding how different cancers alter different trace metals within the body could enable us to develop both new diagnostic tools and new treatments that could lead to a ‘two-pronged’ attack on many cancers. Further research is already underway to see what changes in other metals may be caused by other cancers.’

A report of the research, entitled ‘Zinc isotopic compositions of breast cancer tissue’, is published in the journal Metallomics.