An Overview Of The Cancer Problem

What is commonly called 'human cancer' comprises in fact more than 200 different diseases. Together, they account for about one fifth of all deaths in the industrialized countries of the Western World. Likewise, one person out of three will be treated for a severe cancer in their life-time. In a typical Western industrialized country like Germany with its 82 million inhabitants, >400,000 persons are newly diagnosed with cancer each year, and «200,000 succumb to the disease. Since the incidence of most cancers increases with age, these figures are going to rise, if life expectancy continues to increase.

If one considers the incidence and mortality by organ site, while ignoring further biological and clinical differences, cancers fall into three large groups (Figure 1.1). Cancers arising from epithelia are called 'carcinomas'. These are the most prevalent cancers overall. Four carcinomas are particular important with regard to incidence as well as mortality. Cancers of the lung and the large intestine (colon and rectum, ^■13) are the most significant problem in both genders, together with breast cancer (^■18) in women and prostate cancer (^19) in men. A second group of cancers are not quite as prevalent as these 'major four' cancers. They comprise carcinomas of the bladder (^14), stomach (^17), liver (^16), kidney (^15), pancreas, esophagus, and of the cervix and ovary in women. Each accounts for a few percent of the total cancer incidence and mortality. Each of them is roughly as frequent as all leukemias or lymphomas (^10) taken together. The most prevalent cancers are those ofthe skin (^12), not shown in figure 1.1. They are rarely lethal, with the important exception of melanoma. Cancers of soft tissues, brain, testes, bone, and other organs are relatively rare; but can constitute a significant health problem in specific age groups and geographic regions. For instance, testicular cancer is generally the most frequent neoplasia affecting young adult males, with an incidence of >1% in this group in some Scandinavian countries and in Switzerland.

The health situation in less-industrialized countries differs principally from that in the highly industrialized part of the world because of the continuing, recurring or newly emerged threat of infectious diseases, which include malaria, tuberculosis, and AIDS. Nevertheless, cancer is important in these countries as well, with different patterns of incidence and often higher mortalities. Cancers of the stomach (^17), liver (^16), bladder (^14), esophagus, and the cervix are each endemic in certain parts of the world (Figure 1.2). Often, they manifest at younger ages than in industrialized countries. Conversely, of the major four cancers in industrialized countries, only lung cancer has the same impact in developing countries.

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Figure 1.1 Incidence (top) and mortality (bottom) of cancers (cases per year) by organ site for females (grey bars) and males (black bars) in Germany in 2000. Data are from the Robert Koch Institute (www.rki.de).

This snapshot view of present-day cancer incidence of course conceals changes over time (Figure 1.3). For instance, large-scale industrialization and the spread of cigarette smoking are generally associated with an increased incidence of lung, kidney, and bladder cancer. On the positive side, improvements in general hygiene and food quality may have contributed to the spectacular decrease in stomach cancer incidence that is continuing in industrialized countries (—>17.1). On the negative side, prostate and testicular cancer appear to have increased over the last decades. In prostate cancer, a slight increase in the age-adjusted incidence is exacerbated by the overall aging of the population (^19.1).In some regions, the incidence of melanoma has escalated in an alarming fashion. This increase is not related to the aging of the population, but perhaps to life-style factors (^12.1).

One important aim of molecular biology research on human cancers is to understand the causes underlying the geographical and temporal differences in cancer incidence. This understanding is one important prerequisite for cancer prevention (^20). Obviously, the prospects for prevention are brightest for those cancers that exhibit large geographical differences or the great changes over time in their incidences. To give just one example: The incidence of prostate cancer of East Asia residents may be 10-20-fold lower than that of their relatives who grow up in the USA (—>19.1). It is easy imagining the potential for prevention, if the causes for this difference were understood.

Unfortunately, overall, neither incidence nor mortality of human cancer have been much diminished by conscious human intervention over the last decades. The mainstay of treatment of the 'big four' cancers and of the carcinomas in the second group outlined above remain surgery, radiotherapy, and chemotherapy, as they were 30 years ago. Surgery and radiotherapy are often successful in organ-confined cases, and chemotherapy is moderately efficacious for some advanced cancers. In general, only modest improvements have been made in cure and survival rates for these. Importantly, the quality of life for the patients is now widely accepted as a criterion

Figure 1.2 Mortality of selected cancers by organ site in different regions of the World In each group of bars from left to right: World average, Africa, North-America, South-America, North-West Europe, China. Data source: Shibaya et al, BMC Cancer 2, 37ff

for successful therapy. Modern cancer therapy recognizes that not every malignant tumor can be cured by the means presently available. So, treatment needs to be carefully chosen to maximize the chance for a cure while retaining a maximum of life quality. Providing a better basis for this choice will perhaps constitute the most immediate application of new insights on the molecular biology of cancers (^21). In addition, palliative treatments have become more sophisticated and pain medications are less restrictively administered. Nevertheless, the treatment of metastatic carcinomas remains the weakest point of current cancer therapy and a crucial goal of cancer research (^22).

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Figure 1.3 Trends in the mortality of selected cancers in the USA The original data figure is from the American Cancer Society.

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Figure 1.3 Trends in the mortality of selected cancers in the USA The original data figure is from the American Cancer Society.

Great steps towards successful treatment have been made with specific cancers, unfortunately mostly from the third group above. These improvement have had little effect on the impact of cancer on the overall population, but have helped many individuals, often young people and children. Formerly incurable leukemias and lymphomas can now be successfully treated by chemotherapy and/or stem cell transplantation, particularly in children and young adults. Likewise, the rise in testicular cancer incidence is stemmed by highly efficacious chemo- and radiotherapy, with cure rates exceeding 90%. Obviously, there is a need to understand why these cancers, but not others respond so well to the chemotherapeutic drugs currently available. It is hoped that a better understanding of the molecular and cellular basis underlying this difference will eventually open the door to successful treatment of the major carcinomas, as will the development of novel drugs and novel therapies based on the results of molecular biological cancer research (^22).

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