Über die Autorin bzw. den Autor

Sotiris Missailidis, The Open University

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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.

Aus dem Klappentext

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.

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The Cancer Clock

John Wiley & Sons

Chapter One

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...