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A variety of approaches are used to study carcinogenesis. Recent advances in techniques for culture of human tissues and cells have provided additional experimental systems of study the process of carcinogenesis and the genetics of cancer.

The prevalence of gestational trophoblastic tumors varies widely among different populations: it is lowest in whites (3 to 6/100,000) and highest in Chinese (68 to 202/100,000). This observation suggests that the origin of the disease is different in the two populations. To test this hypothesis, we examined couples in whom the woman developed a gestational trophoblastic tumor in a white population (Pittsburgh) and a Chinese population (Taiwan) for sharing of human leukocyte A, B, DR, and DQ antigens, which we consider markers for sharing of major histocompatibility complex-linked recessive genes affecting both embryogenesis and carcinogenesis. No human leukocyte antigen sharing occurred between partners in Pittsburgh, but there was significant human leukocyte antigen sharing in Taiwan. The latter couples shared human leukocyte antigen B (p less than 0.04) and human leukocyte antigen DQ (p less than 0.007) and shared three or more human leukocyte A, B, DR, and DQ antigens (p less than 0.02) significantly more frequently than did normal couples. However, there was no increased sharing of any specific human leukocyte antigen allele. These findings support the hypothesis that gestational trophoblastic tumors occur on a sporadic basis in whites and on a genetic basis in Chinese.

IT HAS been known for many years that an important aspect in the susceptibility to different forms of cancer is that which deals with hereditary factors. The nature of this inheritance is still unsettled in many respects. The purpose of this article is to tabulate the results of the various investigations and to place before the reader the different theories on the inheritance of cancer. Since most of the results have been explained in terms of genetics, the principles of that science should be applied to any experiment, not only in regard to the material used but also to the interpretation given. Perhaps the most important of these principles to be considered in cancer experimentation work is that of the homogeneity of the stocks. In working with animals it is usually considered that a stock has attained a high degree of homozygosity after fourteen generations of brother-to-sister matings. This method of mating is employed by most geneticists. The difficulty of obtaining homogeneity is emphasized in the following quotation taken from East and Jones (I919)

As the process of tumor progression proceeds from the normal cellular state to a preneoplastic condition and finally to the fully invasive form, the molecular characteristics of the cell change as well. These characteristics can be considered a molecular fingerprint of the cell at each stage of progression and, analogous to fingerprinting a criminal, can be used as markers of the progression process. Based on this premise, the Cancer Genome Anatomy Project was initiated with the broad goal of determining the comprehensive molecular characterization of normal, premalignant, and malignant tumor cells, thus making a reality the identification of all major cellular mechanisms leading to tumor initiation and progression ([Strausberg, R.L., Dahl, C.A., and Klausner, R.D. (1997). “New opportunities for uncovering the molecular basis of cancer.” Nat. Genet., 16: 415-516.], www.ncbi.nlm.nih.gov/ncicgap/ ). The expectation of determining the genetic fingerprints of cancer progression will allow for 1) correlation of disease progression with therapeutic outcome; 2) improved evaluation of disease treatment; 3) stimulation of novel approaches to prevention, detection, and therapy; and 4) enhanced diagnostic tools for clinical applications. Whereas acquiring the comprehensive molecular analysis of cancer progression may take years, results from initial, short-term goals are currently being realized and are proving very fruitful.

Ataxia-telangiectasea (AT), a progressive and uniformly fatal inherited neuroimmunological disorder, affects approximately 1 in 40 000 children. Patients are born to normal parents and appear to develop normally for about two years. They then begin to stagger (ataxia) and show signs of degenerating cerebellar function; by five years of age, they have dilated blood vessels (telangiectases) over the exposed bulbar conjunctiva and skin of the ear. By 10 years of age, they are usually confined to a wheel-chair. Most AT patients have IgA and IgG2 deficiency as well as various T cell-associated immune dysfunctions. Because one of every five patients develops cancer, usually lymphoid, during their shortened life-span, it is believed that unravelling the pathogenesis of AT will also shed light upon the genetics of cancer susceptibility and upon the relationship of immunodeficiency to oncogenesis. A recent conference ∗ ∗A Kroc Foundation conference held on 16–20 January 1984 at Solvang, California. Ray A. Kroc, the founder of the foundation and of McDonald's food chain, died on 14 January 1984. focused on four areas of this complex disorder: DNA repair/replication, genetics, neuropathology and immunopathology.

Retroviruses cause cancer by several different mechanisms including addition of an oncogene, addition of a modified viral glycoprotein, activation of a proto-oncogene, transactivation of a proto-oncogene, immune depression, and stimulation of lymphoid cell proliferation. Both the evolution of oncogenes and tumor induction by most retroviruses is multi-step. Study of the evolution of a particular oncogene, v-rel, indicates that this evolution could not have been selection-driven, but that it resulted from the high rate of mutation in retrovirus replication, that is, it was mutation-driven. Argument is made that much other cancer is also mutation-driven.

Based upon observations on 48 cases of retinoblastoma and published reports, the hypothesis is developed that retinoblastoma is a cancer caused by two mutational events. In the dominantly inherited form, one mutation is inherited via the germinal cells and the second occurs in somatic cells. In the nonhereditary form, both mutations occur in somatic cells. The second mutation produces an average of three retinoblastomas per individual inheriting the first mutation. Using Poisson statistics, one can calculate that this number (three) can explain the occasional gene carrier who gets no tumor, those who develop only unilateral tumors, and those who develop bilateral tumors, as well as explaining instances of multiple tumors in one eye. This value for the mean number of tumors occurring in genetic carriers may be used to estimate the mutation rate for each mutation. The germinal and somatic rates for the first, and the somatic rate for the second, mutation, are approximately equal. The germinal mutation may arise in some instances from a delayed mutation.

Publisher Summary Cancer is a physiologic character involving growth processes. It is the result of a chain of processes directed by both environmental and genetic factors. In this chapter, hybridization studies of various types of tumors are discussed, such as mammary tumors, lung tumors, leukemia, subcutaneous tumors, gastric tumors, tumors of the fowl, tumors of fishes, and tumors in drosophila. It highlights the present knowledge of the genetics of cancer. Both, spontaneous and induced tumors are considered, since in many cases the same genic differences appear to influence both. The genetics of tumor transplantation is not covered as it is a separate subject worthy of separate consideration.

Background Carcinogenesis is widely thought to originate from somatic mutations and an inhibition of growth suppressors, followed by cell proliferation, tissue invasion, and risk of metastasis. Fewer than 10% of all cancers are hereditary; the ratio in gastric (1%), colorectal (3-5%) and breast (8%) cancers is even less. Cancers caused by infection are thought to constitute some 15% of the non-hereditary cancers. Those remaining, 70 to 80%, are called “sporadic,” because they are essentially of unknown etiology. We propose a new paradigm for the origin of the majority of cancers. Presentation of hypothesis Our paradigm postulates that cancer originates following a sequence of events that include (1) a pathogenic stimulus (biological or chemical) followed by (2) chronic inflammation, from which develops (3) fibrosis with associated changes in the cellular microenvironment. From these changes a (4) pre-cancerous niche develops, which triggers the deployment of (5) a chronic stress escape strategy, and when this fails to resolve, (6) a transition of a normal cell to a cancer cell occurs. If we are correct, this paradigm would suggest that the majority of the findings in cancer genetics so far reported are either late events or are epiphenomena that occur after the appearance of the pre-cancerous niche. Testing the hypothesis If, based on experimental and clinical findings presented here, this hypothesis is plausible, then the majority of findings in the genetics of cancer so far reported in the literature are late events or epiphenomena that could have occurred after the development of a PCN. Our model would make clear the need to establish preventive measures long before a cancer becomes clinically apparent. Future research should focus on the intermediate steps of our proposed sequence of events, which will enhance our understanding of the nature of carcinogenesis. Findings on inflammation and fibrosis would be given their warranted importance, with research in anticancer therapies focusing on suppressing the PCN state with very early intervention to detect and quantify any subclinical inflammatory change and to treat all levels of chronic inflammation and prevent fibrotic changes, and so avoid the transition from a normal cell to a cancer cell. Implication of the hypothesis The paradigm proposed here, if proven, spells out a sequence of steps, one or more of which could be interdicted or modulated early in carcinogenesis to prevent or, at a minimum, slow down the progression of many cancers.

In this paper, I examine the historical development of a clinical test for `familial adenomatous polyposis' (FAP), an inherited condition which often leads to cancer of the colon. By paying attention to continuities and changes, especially in the engagement between those medical professionals and patients involved in the development of this test, I reconsider the relationship between knowledge and practice, with an eye to Michel Foucault's and Paul Rabinow's competing notions of `bio-power' and `biosociality'. I conclude by offering some speculative suggestions for further avenues of inquiry into the constitution of the `subject'.

Retroviruses cause cancer by several different mechanisms including addition of an oncogene, addition of a modified viral glycoprotein, activation of a proto-oncogene, transactivation of a proto-oncogene, immune depression, and stimulation of lymphoid cell proliferation. Both the evolution of oncogenes and tumor induction by most retroviruses is multi-step. Study of the evolution of a particular oncogene, v-rel, indicates that this evolution could not have been selection-driven, but that it resulted from the high rate of mutation in retroviruses replication, that is, it was mutation-driven. Argument is made that much other cancer is also mutation-driven.

The primary objective of this volume is to inform the layman more adequately about cancer, with the hope that he may develop better lines of communication with his family physician. The content appears suitable and quite complete for such a purpose, and it is likely that the book will be used by the practitioner to supplement his communication with the patient and his family. The initial chapters are of a general nature and deal with the pathology and genetics of cancer, public attitudes toward the disease, carcinogenic agents, and quackery. The chapter on genetics is one which will answer most of the common questions about the inheritance of cancer which are asked of the physician. Chapters 6 through 15 describe the detection, diagnosis, and treatment of malignancy of the various organ systems in which most neoplasms occur. The material on cervical cancer and the Pap smear, cancer of the breast