The roots of the modern-day study of cancer risk lie all the way back in the nineteenth century at a nunnery in Italy. It was here in 1842 that a doctor called Rigoni-Stern noticed that nuns virtually never suffered from cervical cancer but had a higher than usual incidence of breast cancer, and wondered whether the explanation might lie in the nuns’ celibacy. His observation was an important step toward identifying and understanding the role sexually-transmitted infections and hormones play in cancer risk. It also marked the birth of epidemiology – the study of how behaviours and exposures affect risk of disease.
Now, epidemiologists, such as Professor Anthony Swerdlow, who leads the aetiological epidemiology team here at The Institute of Cancer Research, London, are examining the causes of cancers through epidemiological studies that track large numbers of people over long periods of time – and one of the biggest focuses on breast cancer.
Breast cancer is caused by a complex mix of factors – genetics, environmental factors and aspects of behaviour such as the number of children a woman has and whether she breastfeeds. These factors act at many different stages of life, probably starting before birth, and continuing to the menopause and beyond. The Breakthrough Generations Studyinvolves over 110,000 women aged 16 years and above from the UK, and is collecting data on the environmental, behavioural, hormonal and genetic causes of breast cancer over a 50-year period. Professor Swerdlow explains: “Results from this study are now coming in, and we know that the age of menarche – when a girl’s menstrual periods begin – and menopause are both associated with risk of the disease. Disease risk increases with younger age at menarche and older age at menopause, possibly because these women are exposed to high levels of female sex hormones for a longer period of time.” He adds: “We have found in the Generations Study that the age of menarche was earlier in women born in the 1980s and 90s compared with their mothers’ and grandmothers’ generations. Furthermore, the socioeconomic gradient of age at menarche has reversed: whereas on average a young age at menarche used to be a higher socioeconomic group characteristic, the opposite is true for those born more recently. We know body weight is linked to age of menarche, so increasing numbers of overweight children could have played a part in these changes.” Results like these can help to understand why breast cancer incidence continues to rise and may allow researchers to develop strategies for preventing the disease in the future.
Compared with the 48,000 women who develop breast cancer in the UK each year, the incidence of breast cancer in men is relatively rare – around 350 men per year. As the disease is uncommon in men, the causes are poorly understood. “We are studying men with and without breast cancer, to try to identify the causes of breast cancer in men, as well as the genetics of the disease,” Professor Swerdlow says. “We will also be relating these findings to female breast cancer. We found that a genetic variant at RAD51B can increase the risk of the disease by about 50% in men, and changes in a variant at RAD51B have also been shown to raise the risk of breast cancer in women, although the percentage increase in risk was much less in women. Although there are similarities between causation of male and female breast cancer, there may also be instructive differences.”
As well as being a primary cancer, breast cancer can also occur as a second cancer. Second cancers are the greatest single cause of death in long-term survivors of Hodgkin disease – a type of lymphoma that causes enlargement of lymph nodes, spleen, or other immune tissue. To investigate this further, Professor Swerdlow conducted a landmark study that found women undergoing radiotherapy for Hodgkin lymphoma had an increased risk of developing breast cancer the closer their treatment is to their age of menarche. Women who had radiotherapy treatment to their chest at ages about 10–14 were at particularly high risk of developing breast cancer. “Improved treatments for Hodgkin lymphoma over the last few decades mean that many more women are surviving for longer, but subsequently they may develop second malignancies such as breast cancer,” Professor Swerdlow says. “Results from this study now inform us that these high risks should be considered when planning treatment and screening regimens for women diagnosed with Hodgkin lymphoma at ages near to their menarche.”
Although cancer epidemiology has its roots in the nineteenth century, it is a relatively new science – maturing only in the last half of the 20th century. Yet it has already contributed greatly to our understanding of the patterns and risks of different types of cancers and the evaluation of preventive measures. Those first observations in Italian nuns were the first step in a road that has now led to a vaccine for cervical cancer targeted at the sexually transmitted HPV virus. Scientists hope our expanding knowledge of epidemiology can deliver preventative strategies for other forms of cancer too.