how can the observed environmental effects on cancer rates be exploited to reduce avoidable cancers?
Can new technologies be devised to reveal exactly how a quiescent micrometastasis converts to a full-blown metastatic tumor?
20–1 The chemical carcinogen dimethylbenz[a]anthra-20–4 The main environmental causes of cancer are the cene (DMBA) must be an extraordinarily specific mutagen products of our highly industrialized way of life such as since 90% of the skin tumors it causes have an A-to-T alter-pollution and food additives. ation at exactly the same site in the mutant Ras gene.
Discuss the following problems. 20–2 In the cellular regulatory pathways that control 20–5 In contrast to colon cancer, whose incidence cell growth and proliferation, the products of oncogenes increases dramatically with age, incidence of osteosarare stimulatory components and the products of tumor coma—a tumor that occurs most commonly in the long suppressor genes are inhibitory components. bones—peaks during adolescence. Osteosarcomas are rel atively rare in young children (up to age 9) and in adults 20–3 Cancer therapies directed solely at killing the rap-(over 20). Why do you suppose that the incidence of osteoidly dividing cells that make up the bulk of a tumor are sarcoma does not show the same sort of age-dependence unlikely to eliminate the cancer from many patients. as colon cancer?
lung cancer mortality, cumulative risk (%)
Figure Q20–1 Cumulative risk of lung cancer mortality for nonsmokers, smokers, and former smokers (Problem 20–6). Cumulative risk is the running total of deaths, as a percentage, for each group.
Thus, for continuing smokers, 1% died of lung cancer risk of 5%); and 11% more cumulative risk of 16%).
20–6 Mortality due to lung cancer was followed in groups of males in the United Kingdom for 50 years. Figure Q20–1 shows the cumulative risk of dying from lung cancer as a function of age and smoking habits for four groups of males: those who never smoked, those who stopped at age 30, those who stopped at age 50, and those who continued to smoke. These data show clearly that individuals can substantially reduce their cumulative risk of dying from lung cancer by stopping smoking. What do you suppose is the biological basis for this observation?
20–7 A small fraction—2 to 3%—of all cancers, across many subtypes, displays a quite remarkable phenomenon: tens to hundreds of rearrangements that primarily involve a single chromosome, or chromosomal region. The breakpoints can be tightly clustered, with several in a few kilobases; the junctions of the rearrangements often involve segments of DNA that were not originally close together on the chromosome. The copy number of various segments within the rearranged chromosome was found to be either zero, indicating deletion, or one, indicating retention.
You can imagine two ways in which such multiple, localized rearrangements might happen: a progressive rearrangements model with ongoing inversions, deletions, and duplications involving a localized area, or a catastrophic model in which the chromosome is shattered into fragments that are stitched back together in random order by nonhomologous end joining (Figure Q20–2).
A. Which of the two models in Figure Q20–2 accounts more readily for the features of these highly rearranged chromosomes? Explain your reasoning.
B. For whichever model you choose, suggest how such multiple rearrangements might arise. (The true mechanism is not known.)
C. Do you suppose such rearrangements are likely to be causative events in the cancers in which they are found, or are they probably just passenger events that are unrelated to the cancer? If you think they could be driver events, suggest how such rearrangements might activate an oncogene or inactivate a tumor suppressor gene.