ALL-PARTY PARLIAMENTARY GROUP ON OBESITY

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1 ALL-PARTY PARLIAMENTARY GROUP ON OBESITY Report Wednesday March 16 th 2005 OBESITY AND DISEASE Obesity and Cancer Officers: Contact: Co-Chairs: Dr Howard Stoate MP & Mr Vernon Coaker MP Vice Chair: Mr Michael Fabricant MP Mrs Helen Johnson National Obesity Forum, PO Box 6625, Nottingham, NG2 5PA Tel/Fax The All-Party Parliamentary Group on Obesity is supported by The National Obesity Forum

2 ALL-PARTY PARLIAMENTARY GROUP ON OBESITY OBESITY AND CANCER Wednesday March 16 th 2005 The All-Party Parliamentary Group on Obesity is supported by The National Obesity Forum Introduction This is the report of a meeting of the All Party Parliamentary Group on Obesity, held at the House of Commons on Wednesday March 16 th In 2005, the All Party Parliamentary Obesity Group is holding a series of meetings around the common theme of obesity and disease. Wherever possible, the group will be collaborating with other relevant All Party Groups and involving as wide a range of speakers from advocacy, research and professional organisations as possible. At the end of the series of meetings, the APPG will publish a report of the presentations and discussions that have taken place. The first meeting in the series (February 9 th 2005) looked at obesity, cholesterol and stroke. This meeting, the second in the series, considered the relationship between diet, obesity and different forms of cancer. Two speakers addressed the meeting: o Dr Jonathan Pinkney - Senior Lecturer, University of Liverpool and Consultant Physician at University Hospital Aintree o Professor Tim Key - Cancer Research UK Epidemiology Unit, University of Oxford Over 20 people attended the meeting, representing a wide range of commercial and public sector organisations, government agencies, MPs, academics and healthcare professionals. A list of the organisations represented is appended. Speaker Presentations Dr Jonathan Pinkney Obesity as risk factor for premature death Dr Pinkney opened the meeting first by reviewing the evidence, now well established and widely accepted, that obesity is a major cause of premature mortality of all causes (Figure 1). However, for many years the precise reasons for this premature mortality were not clearly defined, although it was generally assumed that the majority of deaths were likely to be from cardiovascular disease many of those individuals also having type 2 diabetes. Figure 1: Body Mass Index and the relative risk of death from all causes (Modified from G. Bray, 1998). 2

3 Obesity as a risk factor for cancer While type 2 diabetes mellitus is clearly recognised as one of the co-morbid diseases most strongly associated with obesity, the associations between obesity and cancer has generally received far less attention over the years. Until relatively recently, the data on the relationship of obesity with cancer was somewhat fragmentary and, in some instances, conflicting. Some, but not all, studies had found associations between various measures of obesity and the incidence of, or death rates from, a variety of different cancers. Although in absolute terms obesity is a less powerful risk factor for cancer than is, say, cigarette smoking in the case of lung cancer, the relationship between obesity and cancer applies to many different cancers. Clearly, with the rapid rise in the BMI of the UK population, there is potential for that rise in obesity to translate over time into increased incidence and/or deaths from several common cancers. Recently, the Cancer Prevention Study has examined the relationship between obesity and mortality from individual cancers in large numbers of people in North America (Calle, EE et al. N Engl J Med 2003;348: ). Remarkably, and to many, unexpectedly, the relative risk of dying was significant for most tumour types (with the exception of lung cancer, for which the major risk factor is, of course, cigarette smoking). To calculate relative risk of cancer death, Calle and her colleagues made a comparison was made, for example, between subjects in the highest body-mass-index (BMI) category and those in the reference category (body-mass index, 18.5 to 24.9 i.e. normal). This study concluded, for example, that the relative risk of death from uterine cancer was 6.25 times higher in obese women than in women of healthy weight. In the case of cervical and breast cancers, the relative risk of death was 3.2 times and 2.12 times, respectively. Figure 2 shows the summary of the data for all cancers in men and women from the editorial that accompanied these results in the New England Journal of Medicine. Also, unexpectedly, it was observed that deaths from several less common cancers, including bone marrow disorders such as leukaemia and myeloma, were apparently more common in overweight and obese people. The reasons why many cancers are more common in obese people are open to debate, and worthy of further research. It plausible that some cancers are more common in obese people, owing to hormonal changes in the obese state (also see below); alternatively however, it is also possible that some cancers may simply present later in obese people; another possibility is that obese people are less able to withstand some of the treatments for cancer, whether these are surgical or onerous medical treatments such as chemotherapy. 3

4 Figure 2: Relative risk of dying from all cancers versus Body Mass Index. Figure shows the contribution of overweight and obesity to cancer mortality in the United States. Data are from 1,184,617 men and women enrolled in the Cancer Prevention Study II, (Adami H-O, and Trichopoulos D. Editorial. N Eng J Med 2003;348: ). Colorectal cancer: An example of a cancer influenced by obesity Epidemiologically, there is a clear and well-established link between increasing weight and colorectal cancer deaths. Eugenia Calle and her colleagues (Calle, EE et al. N Engl J Med 2003;348: ) examined deaths from colorectal cancer in men and women in the US. Their data showed that the death rate in very obese women (standardised across the study population) was 63.11, compared to a rate of only per 100,000 in lean women. In men who were very obese, the death rate was per 100,000; nearly double the rate in lean men (53.51 deaths per 100,000). Turning to the UK picture, colorectal cancer is a disease of major economic importance to the country, as well as personal significance to its sufferers. There were 35,300 new cases of colorectal cancer diagnosed in the UK in the year 2000, of which 62% were colonic and 38% rectal cancers. Some basic UK statistics (from Cancer Research UK) about this disease are as follows: Incidence increases with age: the over-60s account for 85% of cases of colorectal cancer Males are more likely then women to develop this form of cancer over the age of 40. The incidence is higher in Scotland and Wales than in England. The incidence of colorectal cancers in men increased by 1% a year between There were 16,220 UK deaths from colorectal cancer in 2002; a death rate 27.5 per 100,000 population The 5-year survival rate has improved to around 50% (probably related to earlier detection from better screening and investigation). 4

5 The epidemiological data from the US suggests that increasing obesity has the potential to lead to a gradual increase in colorectal cancer. It is not possible to prove why colorectal cancers have increased in UK males, although it is possible that increasing obesity is one contributing factor. Mechanisms linking obesity to increased risk of cancer death There is a correlation between weight and relative risk of dying from many forms of cancer. Roughly speaking, being overweight increases the rate of cancer deaths by around 20% compared with lean normal weight persons. However, we do not yet understand WHY this link exists. A number of possible theories have been put forward to explain the impact that weight has on cancer mortality, including: An increased risk of tumour formation (e.g. increased exposure to dietary carcinogens)an increased risk of tumour progression (obesity results in complex hormonal changes such as increases in blood levels of oestrogens which promote the growth of certain cancers) Associated social or environmental factors (e.g. sedentary lifestyle, passive smoking) Socio-economic factors which might, for example, result in a later diagnosis of cancer Poorer treatment outcomes What is also apparent is that weight loss has the reverse effect on the risk of dying from cancer. A study that looked at the impact of intentional weight loss on obesity-related health problems in women, found that women losing between 1-8kg in weight reduced their risk of dying from cancer by nearly 30%. Women losing more than 9kg in weight reduced their risk by over 35%. In conclusion Obesity is a modest independent risk factor for most non-smoking related cancers Obesity is likely to impact the future costs of cancer care Prevention of weight gain is likely to prevent cancer Weight loss reduces the risks of cancer The control of weight gain, through the adoption of healthier diet and lifestyles, mainly in lean and overweight people, could make an important contribution to cancer prevention in the UK Professor Tim Key According to Richard Doll & Sir Richard Peto, 2003 data suggests that diet is the second highest contributing factor of cancer deaths (after smoking), accounting for 25% of cancer deaths (see Figure 3). There is, however, more evidence of a link with some cancers than others. Dr Pinkney has already outlined the link between obesity and colorectal cancer deaths and there is certainly great scientific interest in links between diet and deaths from prostate and breast cancer as well. What is established? What do we know for certain? First, scientists do know that: Alcohol consumption increases the risk of developing certain types of cancer o Alcohol has a large effect on mouth, throat, oesophagus cancers o Alcohol has a small effect on breast cancer Smoking and alcohol cause cancers of the mouth, throat and oesophagus Stomach cancer can be caused by infection with Helicobacter pylori, as well as saltpreserved foods, and low consumption of fruit and vegetablesobesity increases risk for some cancers e.g. adenocarcinoma of the oesophagus 5

6 The consumption of fruit, vegetables and meat may also play a role in certain types of cancer, but more research is needed to be certain of that. The European Prospective Investigation into Cancer and Nutrition (EPIC) study has been designed to do just that. Figure 3: Proportion of cancer deaths attributable to environmental and behavioural factors in the UK Tobacco Diet Hormonal Alcohol Infections Ionizing radiation Occupation Pollution Ultraviolet light Adapted from Doll and Peto, Percent The EPIC study The EPIC study is the largest epidemiological study in the world and has been running for more than ten years. The initial results are just starting to come through now. The study is taking place in 10 different European countries (Britain, Denmark, France, Germany, Greece, Italy, Norway, Spain, Sweden, The Netherlands) to provide access to a wide range of dietary patterns. Of the 500,000 participants, about 25,000 have developed cancer since joining the study in Investigators are now trying to establish whether any dietary factors could have increased their risk of developing cancer. Obesity and Colorectal Cancer If one considers the relationship between obesity and colorectal cancer, available data suggest that there are clear differences between male and females. Obesity is a clear, definite risk factor for men, but the effect in women appears to be very small. This suggests that there are other risk factors at play besides obesity or that something is occurring in the biology of the disease which results in these gender differences. For example, it is well known that hormone replacement therapy reduces the risk of colorectal cancer and only women receive HRT. Obesity and Breast Cancer If one considers breast cancer, it is clear that hormones are the key factor: childbearing and breastfeeding are protective, whilst an early menarche, tall height and childhood growth history are all known to increase the risk of developing breast cancer. Both alcohol consumption and obesity are established dietary risk factors, but obesity seems to increase risk only in postmenopausal women (where the increased risk of developing breast cancer is nearly 50%). 6

7 There are lots of studies to show this relationship. For example, the EPIC study has evaluated data from 180,000 women across 10 countries. Over a five-year period, 2000 new cases of breast cancer developed. In premenopausal women, the data showed no significant association between obesity and breast cancer risk. In postmenopausal women, however, risk increased by nearly 50% in those women who were obese. Scientists already know that there is a clear relationship between blood oestrogen levels and increased breast cancer risk. It is also known that obese women who are post-menopausal actually have higher levels of oestrogen than thin postmenopausal women. This is because in postmenopausal women oestrogen is produced by the fat cells, not the ovaries. In premenopausal women (who have 10 times the oestrogen levels of post-menopausal women), body mass index (BMI) does not seem to increase the amount of oestrogen in the blood (see figure 4). The reason obese postmenopausal women are at higher risk is that they have higher oestrogen levels, not just because they are obese per se. Figure 4: Body Mass Index and free oestradiol (oestrogen) Aromatase inhibitors inhibit the production of oestrogen in the fat cells. There is a proposal to try these new drugs in obese women as a prophylactic measure to see if they could prevent breast cancer from developing. Weight gain and weight change are also strongly associated with breast cancer risk; the amount of the gain or the change seems to be more important than the baseline weight. Conversely, there is some definite evidence to support the premise that weight loss can reduce breast cancer risk. From a public health point of view, this is clearly an important message. Obesity and endometrial cancer Oestrogen is known to stimulate cell division and endometrial cancer is even more sensitive to oestrogen levels than breast cancer. Obesity and oestrogen only HRT strongly increase the risk of endometrial cancer, whilst pregnancy and the contraceptive pill reduce the risk. 7

8 Obesity and mortality from cancer Studies show that there is a clear link between cancer mortality/death and obesity, which is stronger than the link between obesity and the relative rate of developing cancer in the first place. This suggests that the obesity impacts on survival rate as well as the risk of developing it in the first place. Outstanding questions A large number of research questions are still outstanding: Looking at the relationship between obesity and cancer o Does the distribution of the fat matter? Does visceral fat carry more risk than adipose fat? o Can physical activity cancel out the risk associated with obesity or do both matter? What are the mechanism for how certain cancers such as colorectal and kidney cancers are related to obesity? How can we reduce obesity and the risks of developing cancer? Cancer Research UK s Reduce the Risk campaign focuses on five key messages: Stop smoking Stay in shape Eat and drink healthily Be sun smart Look after number one Conclusions In conclusion: In breast, endometrial, prostate and colorectal cancers, the effect of obesity on cancer mortality is greater than the effect of cancer incidence. Obesity is clearly a risk factor for these tumour types, but the magnitude of the risk is quite modest compared to the relative risk increase in lung cancer if you smoke (relative risk of about 30 fold increase). The mechanism between obesity and endometrial/ breast cancers is well understood; it s clearly oestrogen-driven. For other cancers, like prostate, although there is a small increase in risk for people who are obese, scientists have yet to determine why, or even whether, the link is causative. Currently, obesity accounts for approximately 5% of all cancer cases in Europe (3% in men, 6% in women) In terms of cancer mortality, obesity accounts for about 14% of cancer deaths in men and 20% of cancer deaths in women in the US. Audience Discussion The following points arose during the audience discussion: How relevant is bowel transit time to the risk of developing colorectal cancer? There have been suggestions that the longer food stays in the gut, the more carcinogenic it could be. Kemp et al published a study on bowel frequency (as opposed to transit time) and 8

9 actually found that obese people had a slightly greater frequency than those of normal weight. So far as the speakers are aware, there is no evidence of a link between obesity in childhood and childhood cancers? However, there are some data on overweight children and the risk of developing breast cancer as adults. High birth weight is positively related to breast cancer risk in adults. Oddly, obese children (studies at ages 7 and 14) might be at lower risk of developing breast cancer as adults than their lean peers. Obesity is associated with fatty livers, but the data on a link between obesity and primary liver cancers is small and inconclusive. There is some evidence that if fat people lose weight, their fatty liver improves. There are difficulties involved in simply telling people they need to lose weight to reduce their risk of developing (or dying from) other diseases. It is not always helpful to tell people to lose weight. Overweight people find it difficult to lose weight or may feel too embarrassed or unsupported to try. Most weight loss schemes focus on food and not behavioural issues. This is not the case for other chronic conditions. For example, cognitive behavioural therapy is readily available as a first line treatment for people with anxiety and depression. Why not for people with eating disorders and obesity? It is wrong to suggest that cancer incidence rates are going up. The incidence varies greatly according to tumour type. For example, the incidence of stomach cancer has actually fallen by 70% over he last 40 years. Moreover, the incidence of colorectal cancer has remained relatively constant and has declined in young men and women. What about socio-economic factors? The incidence of colorectal cancer is not class related and is, in any event, rather constant over time. The incidence of breast cancer is higher in rich women. The incidences of stomach and lung cancers are closely related to social class. Appendix The following organisations were represented at the meeting: Cancer Research UK Cholesterol UK Dairy Council East Elmbridge and Mid-Surrey PCT Fuel PR House of Commons members 9

10 Move4Health National Obesity Forum TOAST University Hospital, Aintree University of Oxford World Cancer Research Fund 10