MWS is uniquely placed to study risk factors for rare cancers
The ovary and endometrium are, respectively, the fifth and fourth most common cancer sites in UK women and the unit has a large programme of research into these and other cancers of the female genital tract. Analyses of data from our two ongoing international collaborations, The Collaborative Group on Epidemiological Studies of Ovarian Cancer and The Collaborative Group on Epidemiological studies of Endometrial Cancer, and from the Million Women Study, have shown that hormones have important causal and preventive effects on both ovarian and endometrial cancer, with use of hormonal contraceptives resulting in strong long-term protection (Beral et al, 2015; Beral et al, 2008), and menopausal hormones having the opposite effect on risk (Beral et al, 2015; Beral et al, 2007; Beral et al, 2005). Bringing together the worldwide epidemiological data on these cancers has also shown that failure to take account of tumour subtype can mask important associations. For example, in our collaborative analyses, smoking was associated with little effect on the overall incidence of ovarian cancer, but with a large increase in mucinous ovarian cancers and a compensatory decrease in endometrioid and clear cell tumours (Beral et al, 2012). Future work will focus on exploring the role of reproductive and other risk factors for both cancers, according to histological type. The Million Women Study is being used to address hypotheses about the aetiology of ovarian and endometrial cancers that cannot be answered by the international collaborations, for example about the effects of diet and certain environmental exposures.
Colorectal cancer is the second most common cancer in the UK but there are few established risk factors for the disease. Extremely low rates of colorectal cancer are found in first, but not second, generation British South Asians, suggesting that there may be large, but still unknown, effects of environmental exposures. We are conducting research within the Million Women study and other existing cohort studies to assess the relationships between colorectal and other gastrointestinal cancers and a wide range of potential risk factors including smoking, alcohol intake, sex hormones, obesity, physical activity and diet within the Million Women Study. To date, results of our analyses suggest that hormonal factors are associated with the development of several gastrointestinal cancers (Green et al, 2012; Green et al, 2012) and that the risk of oesophageal cancer may be increased in users of oral bisphosphonates (Green et al, 2010). The Million Women Study cohort has also been linked to routinely collected data from the NHS bowel screening programme in order to examine the relationship between factors such as education, socio-economic status, smoking habits, diet, and reproductive history, and screening uptake and outcomes.
The extremely large size of the Million Women Study means that we are uniquely placed to examine the aetiology of many relatively rare cancers. Brain cancers and other cancers of the central nervous system (CNS) are uncommon but typically have a poor prognosis. Hormonal factors are thought to play a role in the aetiology of CNS cancers and analyses of Million Women Study data suggest that current users of HRT may be at an increased risk for such tumours (Benson et al, 2010), a finding that was supported by corresponding analyses of data from the UK General Practice Research Database (Benson et al, 2014). Analyses of CNS cancer risk in relation to mobile phone use within the Million Women Study, however, found no evidence of an association with any specific type of tumour, apart from a modest association with the risk of acoustic neuromas (Benson et al, 2013). As sizeable numbers of rare cancer types accrue in the cohort we plan to investigate their relationship with diet, smoking, and other factors.
For those risk factors that have been implicated in the development of many different cancer sites, such as birthweight, height, adiposity and alcohol intake, we have published comprehensive reports based on Million Women Study data comparing their associations with a wide range of cancers (Yang et al, 2014; Green et al, 2011; Reeves et al, 2007; Allen et al, 2009).