The Cancer Clock - Softcover

Softcover

ISBN 10: 0470061529 ISBN 13: 9780470061527

Publisher: Wiley, 2007

Synopsis

Edited by the winner of the 2008 Mike Price Fellowship

The Cancer Clock is a comprehensive overview of cancer as a single topic and provides an all-encompassing account of the key aspects related to the disease from its causes and initial diagnosis through to treatment and care and the different support mechanisms available. Carefully divided into three key parts, the first part of the book focuses on the genesis of the disease through environmental, lifestyle and socioeconomic factors. The second part moves on to consider early disease, disease development, diagnosis, monitoring and imaging of the disease. The book then discusses standard treatments such as surgery, chemotherapy, radiotherapy and immunotherapy along with current developments in the field such as targeted therapeutics, antibody therapies and novel chemotherapy agents. The book closes with a discussion of patient care, pain control, nursing in cancer patients and rehabilitation processes and a final chapter that looks at the psychological and psychosocial aspects of the disease, from coping with the knowledge of having cancer to coping with the side effects of the treatments, family support and dedicated support groups.

Written in a clear, accessible manner this book is an ideal starting point for students of pharmacy, pharmacology, the biomedical sciences and other related disciplines where an understanding of cancer as a whole is required. 

• takes an interdisciplinary approach covering the chemistry, epidemiology, basic biology and genetics, radiology, medical physics, medicine, nursing, health and social welfare all associated with cancer diagnosis, treatment and care
• explains the various causes of cancer and suggests actions for the prevention of the disease
• includes chapters on current diagnostic tests, drug development and the techniques used in drug design both chemical and biological
• considers current experimental therapeutic and diagnostic approaches and their potential for future therapeutic development
• examines aspects of cancer care, physiotherapy, rehabilitation and the psychological aspects of the disease
• includes self assessment questions/answers, summary sections and review questions and information boxes to enhance student understanding

About this title

About the Author

Sotiris Missailidis, The Open University

From the Back Cover

The Cancer Clock is a comprehensive overview of cancer as a single topic and provides an all-encompassing account of the key aspects related to the disease from its causes and initial diagnosis through to treatment and care and the different support mechanisms available. Carefully divided into three key parts, the first part of the book focuses on the genesis of the disease through environmental, lifestyle and socioeconomic factors. The second part moves on to consider early disease, disease development, diagnosis, monitoring and imaging of the disease. The book then discusses standard treatments such as surgery, chemotherapy, radiotherapy and immunotherapy along with current developments in the field such as targeted therapeutics, antibody therapies and novel chemotherapy agents. The book closes with a discussion of patient care, pain control, nursing in cancer patients and rehabilitation processes and a final chapter that looks at the psychological and psychosocial aspects of the disease, from coping with the knowledge of having cancer to coping with the side effects of the treatments, family support and dedicated support groups.

Written in a clear, accessible manner this book is an ideal starting point for students of pharmacy, pharmacology, the biomedical sciences and other related disciplines where an understanding of cancer as a whole is required.

• takes an interdisciplinary approach covering the chemistry, epidemiology, basic biology and genetics, radiology, medical physics, medicine, nursing, health and social welfare all associated with cancer diagnosis, treatment and care.
• explains the various causes of cancer and suggests actions for the prevention of the disease.
• includes chapters on current diagnostic tests, drug development and the techniques used in drug design both chemical and biological.
• considers current experimental therapeutic and diagnostic approaches and their potential for future therapeutic development.
• examines aspects of cancer care, physiotherapy, rehabilitation and the psychological aspects of the disease
• includes self assessment questions/answers, summary sections and review questions and information boxes to enhance student understanding.

Written in a clear, accessible manner this book is an ideal starting point for students of pharmacy, pharmacology, the biomedical sciences and other related disciplines where an understanding of cancer as a whole is required. 

• takes an interdisciplinary approach covering the chemistry, epidemiology, basic biology and genetics, radiology, medical physics, medicine, nursing, health and social welfare all associated with cancer diagnosis, treatment and care.
• explains the various causes of cancer and suggests actions for the prevention of the disease.
• includes chapters on current diagnostic tests, drug development and the techniques used in drug design both chemical and biological.
• considers current experimental therapeutic and diagnostic approaches and their potential for future therapeutic development.
• examines aspects of cancer care, physiotherapy, rehabilitation and the psychological aspects of the disease
• includes self assessment questions/answers, summary sections and review questions and information boxes to enhance student understanding.

Excerpt. © Reprinted by permission. All rights reserved.

The Cancer Clock

By Sotiris Missailidis

John Wiley & Sons

Copyright © 2007 John Wiley & Sons Ltd
All right reserved.
ISBN: 978-0-470-06152-7

Chapter One

Socioeconomic and molecular basis of cancer

David E. G. Shuker

Department of Chemistry, The Open University, UK

1.1 Introduction

Cancer is a disease that is characterized by the slow rate at which it develops. This might seem at odds with our experience of seeing people diagnosed with a cancer seeming, for the most part, to have a short life expectancy. However, the clinical stage of most cancers is literally the 'tip of the iceberg', because the cancer will have been growing undetected for many years in the early stages of its natural history.

As we have come to understand more about the phenomenon of cancer at both the biological and epidemiological level it has become apparent that there are two main factors that influence the risk of developing cancer - time and place.

The importance of time can be seen by looking at the age-specific mortality of cancer at all sites in men and women (Figure 1.1). The age-specific rates of different cancers display similar patterns (with the notable exception of some childhood cancers such as neuroblastoma), namely, the incidence is very low until about 40 years of age and then displays a dramatic rise thereafter. This overall pattern is driven by the profiles of some of the major cancers - the age-specific incidence of colorectal cancer rises relentlessly with age (Figure 1.2). However, within this overall pattern there are some significant differences for particular cancer sites. For example, the incidence of ovarian cancer in women shows a peak at age 70-80 with a noticeable decline thereafter (Figure 1.3). Somewhat more spectacularly, the peak incidence of testicular cancer is seen in men at around age 40 with the incidence at age 70 being not much more than that for young men (Figure 1.4). These exceptions are probably linked to hormonal effects that change throughout lifetime. Note also that the incidence rates (as incident cases per 100 000 individuals of the population, shown on the vertical axes) vary greatly between the different cancers.

So far we have discussed time as it is measured in epidemiological studies. There is another way in which time is important in the cancer process and that is at the molecular and biological level. One of the best characterized cancer progressions is that of colorectal cancer, for which the key molecular steps have been identified. Vogelstein and colleagues at Johns Hopkins University in Baltimore have built up a picture of the natural history of colorectal cancer that can be summarized in a diagram that has become affectionately known as a 'Vogelgram' (Figure 1.5). Colorectal cancers are believed to develop over the course of 20-40 years as a consequence of the episodic accrual of specific mutations in oncogenes such as KRAS (Kirsten Ras) and tumour suppressor genes such as APC (a gene first identified in the hereditary susceptibility to adenomatous polyposis coli) and TP53 (a gene encoding for the p53 tumour suppressor protein). These mutations arise within the tumour in a characteristic sequence. A single cell acquires a mutation in one such gene, and this mutation soon reaches fixation because of the growth advantage it provides to the cell. Genetic instability is thought to occur somewhere during the process of colorectal tumorigenesis to accelerate the rate of mutations in dividing cancer cells. Each of the individual mutations is itself a rare event. For a cancer to progress to the clinical stage, a progenitor cell, or clone of cells, would have to accumulate three or more of these mutations. It is the time that it takes for such a 'jackpot' of rare mutations to occur in sporadic cancers that probably explains why it can take up to 40 years for a cancer to develop. Some evidence for this comes from studies of rare inherited genetic disorders such as the Li-Fraumeni and Lynch syndromes that predispose to the virtually certain development of cancers in early life. In such syndromes mutations in key genes are inherited in the germline so that every cell in the body contains mutated APC or TP53. This circumstance vastly increases the likelihood that a subsequent rare somatic mutation will occur in an already mutated cell.

We now turn our attention to the role of place in influencing cancer risk. The incidence of many cancers varies greatly from country to country and from region to region (Figure 1.6). One possible explanation of this could be that variations in the genetic make-up of different populations would lead to differing susceptibilities to cancer. Alternatively, variations in exposure to environmental carcinogens, or differences in lifestyle because of the range of cultural profiles around the world, might lead to differences in cancer risk. Studies of migrant populations offer the possibility to examine the contributions of these alternative explanations. The genetic profile of individuals within a migrant population will not change within one generation, or within several generations for that matter. In contrast, exposures to environmental carcinogens will change immediately upon arrival and lifestyle changes will follow as assimilation of migrants into a new culture occurs. Thus, cancer risks driven predominantly by genetic factors would show little if any change in migrant populations, whereas those influenced by environmental or lifestyle factors would reflect the changes in the profile of exposures. The available evidence suggests that most cancer risks fit the environmental/lifestyle model of causation rather than the genetic model.

Migrant studies provide compelling evidence that cancer risk is principally determined by environmental factors, including diet. Patterns of cancer among migrant groups, as they move from country to country, often change faster than those within any country. Patterns of diet also change over time as a result of migration, sometimes dramatically.

A classic example of changes in cancer risk, in both directions, for different cancers is found in Japanese migrants to Hawaii (Figure 1.7). Japanese women living in Japan typically have a high risk of stomach cancer and an almost three times lower risk of breast cancer. The first generation of Japanese migrants in Hawaii showed a halving of their stomach cancer risk and an almost trebling of their breast cancer risk. By the second generation the Japanese-Hawaiians had a stomach cancer risk one-third that of women in Japan but a breast cancer risk that was four times higher. In a number of migrant studies a similar pattern has been seen with incoming migrants 'adopting' the profile of cancer risks of the indigenous populations. The rapidity with which cancer risks change is illustrated by a study of breast cancer mortality in Italian women migrants in Australia. Changes in rates of cancer mortality could be seen as soon as 5 years after the arrival of migrants in the host country (Figure 1.8).

In the discussion so far of the effects of time and place on cancer risk we have hinted at a number of environmental, lifestyle and dietary factors as causative, or aetiological agents. We will now turn our attention to a more detailed discussion of the role of certain factors in the determination of cancer risk.

1.2 Diet and cancer

Human beings need to consume a certain amount of food and water each day in order to acquire the basic energy required to keep the system going, as well as obtain the raw materials essential for building and repairing cellular components. The sheer quantity of food consumed by an average British family during a year in the late 1980s is rather impressive (Figure 1.9).

Until quite recently, the 'normal' diet was assumed to be either largely neutral in its effects on cancer risk or, for the most part, beneficial or protective. The role of diet in some other chronic diseases, such as diabetes and coeliac disease, had been long recognized as being linked to the presence of particular food components interacting with a defective metabolic function. In the case of cancer, the available evidence suggested that some cancers were linked to the presence of contaminants of man-made or natural origin. However, despite the public concern about cancer risk from pesticides, arising in large part from the publication of Rachel Carson's book Silent Spring in the 1960s, there is little, if any, evidence that the use of pesticides raises the risk of cancer. This is not to say that pesticides are not toxic or carcinogenic, for many of them are, but the reality of the situation is that the levels of pesticide residues in foods are so low that, for all practical purposes, these exposures do not add perceptibly to the burden of cancer. It is important to note that this conclusion is not based on the extrapolation of data obtained in experimental animals to the human situation but on large epidemiological studies where pesticide exposures were assessed and for which data on cancer outcome were available. Notwithstanding, there is evidence that occupational exposure to pesticides in agricultural workers working with high volumes of concentrated pesticide solutions does lead to a somewhat increased risk of developing non-Hodgkin's lymphoma. Perhaps this is as good an example as any of the well-known aphorism - 'it is the dose that makes the poison' - attributed to the wonderfully named 16th century physician Philippus Aureolus Theophrastus Bombastus von Hohenheim (aka Paracelsus, 1493-1541).

In contrast, there is evidence that exposure to certain naturally occurring toxins, at levels consumed in the diet, does lead to a significantly increased risk of cancer. The aflatoxins, for example, are a group of fungal metabolites that are found in foodstuffs contaminated with Aspergillus fungi. The fungal contamination occurs when the susceptible foodstuffs (maize and groundnuts) are stored in warm and humid climates. There has been concern for along time that human exposure to aflatoxins is a major risk factor for liver cancer but the epidemiology has been confounded by the risks of the same disease due to hepatitis infections. The distinctive chemical structure of aflatoxins has enabled the development of various assays capable of measuring human exposure to these carcinogens. The assays are based on the measurement of urinary metabolites as well as products of the interactions between aflatoxin and proteins or DNA (protein or DNA adducts; Box 1.1).

The demonstration that DNA adducts and other measures of aflatoxin exposure could really contribute to human risk assessment came with the results of a large prospective cohort study in south-east Asia. Between 1986 and 1989, 18 244 men (aged 45-64 years) were recruited into a cohort which was followed up with respect to the occurrence of hepatocellular carcinoma. At recruitment into the study each subject was interviewed, using a questionnaire, for details of dietary and other past exposures. Samples of blood and urine were also collected and stored for future analysis for a number of markers. Over the following years, 55 cases of liver cancer and 267 matched controls were collected and analysed as a nested case-control study. The presence of any urinary biomarker of aflatoxin exposure indicated a four-fold elevated risk of liver cancer. The presence of urinary aflatoxin B1-guanine (AFB1-Gua), derived from the breakdown of specific liver DNA adducts, was linked to an almost eight-fold increase in risk. The combination of urinary AFB1-Gua and specific urinary metabolites of aflatoxins indicated a ten-fold increase in risk. The study also allowed an analysis of the effect of hepatitis. Previous exposure to hepatitis B results in the presence of antibodies to a surface antigen (HBsAg) that can be detected many years after the infection and this antibody is, therefore, a biomarker of the past infection. The simultaneous presence of markers of exposure to aflatoxin and hepatitis indicated an almost 60-fold increase in the risk of developing liver cancer. Interestingly, a classic epidemiological analysis of the questionnaire data for the cases and controls failed to reveal the same effects.

This study dramatically demonstrated the value of using biomarkers of exposure to an environmental carcinogen as means to identify risk factors for a disease outcome with much greater sensitivity than traditional methods of epidemiological enquiry. Having established that certain biomarkers of aflatoxin exposure did indeed have good predictive value for the disease outcome, there are now efforts to use them to evaluate the effect of intervention studies using a drug, oltipraz, which is known from animal studies to reduce the risk of liver cancer caused by aflatoxins.

Whilst the story of aflatoxins and liver cancer is a good example of the identification of a particularly potent foodborne carcinogen, much of the cancer risk associated with diet has proved much more difficult to characterise. There are several problems associated with the study of diet and cancer. First, establishing exactly what constitutes an individual's diet is not as easy to determine as might be thought. Surprisingly, people are very unreliable in their recollection, even within the past 24 hours, of what they ate, particularly with respect to portion size. Studies using biomarkers of protein and salt intake have shown how inaccurate a 24-h dietary recall questionnaire can be. From a practical standpoint, a diet diary, in which all types of food and the quantities consumed are recorded, has been shown to provide an acceptably complete account of what a person really has eaten. Moreover, the use of photographic prompts for portion size has been shown to provide a quantitatively accurate measure of the amount consumed. You may not, however, be surprised to hear that, in the absence of such approaches, people tend to overestimate how much fruit and vegetables they have eaten and underestimate their consumption of meat. Second, it is not particularly obvious what it is about a particularly dietary component that is important for its effect on cancer risk. For example, with respect to meat consumption, is it important to know how the meat was prepared? - was it processed with the addition of additives such as nitrite, leading to the formation of nitrosamines? - was it cooked at a high temperature, leading to the production of mutagenic pyrolysis products? - or is the protein content an important source of precursors for endogenous processes that lead to mutagen formation? Similarly, for fruit and vegetables - is it the frequency and type of fruit/vegetable that is important? - is it the vitamin C/E content? - or, is it the amount of fibre that is important? Third, the level of cancer risk associated with dietary components is usually not very large. This is perhaps not surprising. If a food was strongly associated with cancer, this would have been recognized long ago and its use would have been avoided. This is certainly the case with other chronic and acute diseases - particularly if the cause of the problem is related to food being mouldy or tainted. Thus, the study of links between diet and cancer require large groups of people to be followed over many years (10-20 or more years). Such studies are expensive and do not yield many results in the early stages. However, several large studies were set up in the late 1980s - the Nurses' Health Study in the US and the European Prospective Investigation on Diet and Cancer (EPIC) - and are now beginning to yield important results. The scale of these studies is truly vast - in the second stage of the US Nurses' Health Study there were over 110 000 volunteers and in the entire EPIC cohort there were over 500 000 people recruited. The size of these prospective studies means that nested case-control studies with high statistical power for particular endpoints can be carried out within the cohort. The use of stored biological samples (notably blood and urine) adds further power to these studies, as biomarkers provide objective measures of dietary components. Furthermore, because the studies are prospective, the dietary questionnaires and biological samples were collected when the volunteers were healthy. If such markers are predictive of subsequent cancer risk they have the potential to be used in future studies where dietary interventions designed to reduce cancer risk can be tested.

(Continues...)

Excerpted from The Cancer Clockby Sotiris Missailidis Copyright © 2007 by John Wiley & Sons Ltd . Excerpted by permission.
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Edition details

• Publisher: Wiley
• Publication date: 2007
• Language: English
• ISBN 10: 0470061529
• ISBN 13: 9780470061527
• Binding: Paperback
• Edition number: 1
• Number of pages: 320
• Editor: Missailidis Sotiris