50. people are able to lead more sedentary lives: Even that, however, is controversial. See Herman Pontzer et al., “Hunter-Gatherer Energetics and Human Obesity,” PLOS ONE 7, no. 7 (July 25, 2012): e40503. [http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0040503#abstract0]
51. An official statement from EPIC: “Key Findings,” EPIC Project website. [http://epic.iarc.fr/keyfindings.php]
CHAPTER 11 Gambling with Radiation
1. a wake of corrosive free radicals: Hongning Zhou et al., “Consequences of Cytoplasmic Irradiation: Studies from Microbeam,” Journal of Radiation Research 50, suppl. A (2009): A59–A65. [http://www.ncbi.nlm.nih.gov/pubmed/19346686]
2. send signals to neighboring cells: Hongning Zhou et al., “Induction of a Bystander Mutagenic Effect of Alpha Particles in Mammalian Cells,” Proceedings of the National Academy of Sciences 97, no. 5 (February 29, 2000): 2099–104. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC15760]
3. 13.4 percent, may be radon related: Office of Radiation and Indoor Air, EPA Assessment of Risks from Radon in Homes (Washington, DC: United States Environmental Protection Agency, June 2003), iv, available on the EPA website. [http://www.epa.gov/radon/risk_assessment.html]
4. smoking is also a factor: “Radon and Cancer,” National Cancer Institute website. [http://www.cancer.gov/cancertopics/factsheet/Risk/radon]
5. The EPA’s scale: “Health Risks,” EPA website, last updated June 26, 2012. [http://www.epa.gov/radon/healthrisks.html]
6. clusters of two neutrons and two protons: These are, in fact, helium nuclei. Early on it was noticed that radium emits helium as it decays. See William Ramsay and Frederick Soddy, “Experiments in Radioactivity, and the Production of Helium from Radium,” Proceedings of the Royal Society 72 (1903): 204–7. [http://rspl.royalsocietypublishing.org/content/72/477-486/204.full.pdf]
7. 70 percent of their time at home: EPA Assessment of Risks, 7, 44.
8. The chance of a nonsmoker getting lung cancer: Rebecca Goldin, “Lung Cancer Rates: What’s Your Risk?” March 08, 2006, Research at Statistical Assessment Service (STATS) website, George Mason University. [http://stats.org/stories/2006/lung_cancer_rates_mar08_06.htm]
9. a laboratory analysis of my eyeglasses: R. L. Fleischer et al., “Personal Radon Dosimetry from Eyeglass Lenses,” Radiation Protection Dosimetry 97, no. 3 (November 1, 2001): 251–58. [http://rpd.oxfordjournals.org/content/97/3/251.abstract]
10. a method using ordinary household glass: R. W. Field et al., “Intercomparison of Retrospective Radon Detectors,” Environmental Health Perspectives 107, no. 11 (November 1999): 905–10 [http://www.ncbi.nlm.nih.gov/pubmed/10545336]; D. J. Steck, R. W. Field, et al., “210Po Implanted in Glass Surfaces by Long Term Exposure to Indoor Radon,” Health Physics 83, no. 2 (August 2002): 261–71 [http://www.ncbi.nlm.nih.gov/pubmed/12132714]; and Kainan Sun, Daniel J. Steck, and R. William Field, “Field Investigation of the Surface-deposited Radon Progeny as a Possible Predictor of the Airborne Radon Progeny Dose Rate,” Health Physics 97, no. 2 (August 2009): 132–44. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2836385]
11. as long as they have owned the objects: For a few decades, anyway. The half-life of 210Po, one of the radon products that is measured, is twenty-two years.
12. houses in Grand Junction: Leonard A. Cole, Element of Risk: The Politics of Radon (New York: Oxford University Press, 1994), 10–12.
13. a construction engineer named Stanley Watras: Cole, Element of Risk, 12.
14. A study in Winnipeg: E. G. Létourneau et al., “Case-Control Study of Residential Radon and Lung Cancer,” American Journal of Epidemiology 140, no. 4 (1994): 310–22. [http://aje.oxfordjournals.org/content/140/4/310.abstract]
15. compared the average radon levels: These and other studies are summarized in the Winnipeg paper.
16. a negative correlation: B. L. Cohen, “Test of the Linear-No Threshold Theory of Radiation Carcinogenesis for Inhaled Radon Decay Products,” Health Physics 68, no. 2 (February 1995): 157–74. [http://www.ncbi.nlm.nih.gov/pubmed/7814250]
17. the study was flawed: J. H. Lubin, “On the Discrepancy Between Epidemiologic Studies in Individuals of Lung Cancer and Residential Radon and Cohen’s Ecologic Regression,” Health Physics 75, no. 1 (July 1998): 4–10. [http://www.ncbi.nlm.nih.gov/pubmed/9645660]
18. skewed by an inverse connection: J. S. Puskin, “Smoking as a Confounder in Ecologic Correlations of Cancer Mortality Rates with Average County Radon Levels,” Health Physics 84, no. 4 (April 2003): 526–32. [http://www.ncbi.nlm.nih.gov/pubmed/12705451] For a sampling of the debate that erupted see B. J. Smith, R. W. Field, and C. F. Lynch, “Residential 222Rn Exposure and Lung Cancer: Testing the Linear No-threshold Theory with Ecologic Data,” Health Physics 75, no. 1 (July 1998): 11–17; [http://www.ncbi.nlm.nih.gov/pubmed/9645661] and B. J. Cohen, “Response to Criticisms of Smith et al.,” Health Physics 75, no. 1 (July 1998): 23–28, 31–33. [http://www.ncbi.nlm.nih.gov/pubmed/9645663] Rejoinders and rejoinders to the rejoinders followed.
19. Perhaps cigarette smoke interfered with the radon monitors: R. W. Field, e-mail to author, June 7, 2012.
20. hundreds to thousands of picocuries per liter: Cole, Element of Risk, 28.
21. lung cancer rates among uranium miners: The studies are summarized in “EPA’s Assessment of Risks from Radon,” 8, 11, and in Committee on Health Risks of Exposure to Radon (BEIR VI), National Research Council, Health Effects of Exposure to Radon: BEIR VI (Washington, DC: The National Academies Press, 1999), 76–78. [http://www.nap.edu/catalog.php?record_id=5499]
22. how long or how often they had smoked: BEIR VI, 77, table 3-2.
23. a committee of the National Research Council: BEIR VI, 18.
24. The most ambitious study: R. W. Field et al., “Residential Radon Gas Exposure and Lung Cancer: The Iowa Radon Lung Cancer Study,” American Journal of Epidemiology 151, no. 11 (June 1, 2000): 1091–102. [http://www.cheec.uiowa.edu/misc/radon.html]
25. about 62 cases per 100,000 men and women: “SEER Stat Fact Sheets: Lung and Bronchus,” Surveillance, Epidemiology, and End Results (SEER) Program website. [http://seer.cancer.gov/statfacts/html/lungb.html]
26. Three of the analyses: S. Darby et al., “Radon in Homes and Risk of Lung Cancer: Collaborative Analysis of Individual Data from 13 European Case-control Studies,” BMJ: British Medical Journal 330, no. 7485 (January 29, 2005): 223. [http://www.bmj.com/content/330/7485/223] The results are described in Hajo Zeeb and Ferid Shannoun, eds., WHO Handbook on Indoor Radon: A Public Health Perspective (Geneva: World Health Organization, 2009), 12. [http://www.who.int/ionizing_radiation/env/radon/en/index1.html]
27. consider the matter clinched: For an overview, see Jonathan M. Samet, “Radiation and Cancer Risk: A Continuing Challenge for Epidemiologists,” Environmental Health 10, suppl. 1 (April 5, 2011): S4. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073196]
28. small doses of radiation are … beneficial: Alexander M. Vaiserman, “Radiation Hormesis: Historical Perspective and Implications for Low-Dose Cancer Risk Assessment,” Dose-Response 8, no. 2 (January 18, 2010): 172–91. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2889502] Also see Edward J. Calabrese and Linda A. Baldwin, “Toxicology Rethinks Its Central Belief,” Nature 421, no. 6924 (February 13, 2003): 691–92 [http://www.ncbi.nlm.nih.gov/pubmed/12610596]; L. E. Feinendegen, “Evidence for Beneficial Low Level Radiation Effects and Radiation Hormesis,” British Journal of Radiology 78, no. 925 (January 1, 2005): 3–7 [http://bjr.birjournals.org/content/78/925/3.abstract]; and Jocelyn Kaiser, “Sipping from a Poisoned Chalice,” Science 302, no. 5644 (October 17, 2003): 376–79. [http://www.sciencemag.org/content/302/5644/376.short]
29. A Johns Hopkins researcher recently concluded: Richard E. Thompson, “Epidemiological Evidence for Possible Radiation Hormesis from Radon Exposure,” Dose-Response 9, no. 1 (December 14, 2010): 59–75. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057636]
30. low-level x-ray, gamma, and beta radiation: Bobby R. Scott
et al., “Radiation-stimulated Epigenetic Reprogramming of Adaptive-response Genes in the Lung: An Evolutionary Gift for Mounting Adaptive Protection Against Lung Cancer,” Dose-Response 7, no. 2 (2009): 104–31. [http://www.ncbi.nlm.nih.gov/pubmed/19543479]
31. the Chernobyl nuclear power plant: “Chernobyl’s Legacy: Health, Environmental and Socio-economic Impacts,” The Chernobyl Forum: 2003–2005, 2nd revised version, 2012. Available on the International Atomic Energy Agency website. [http://www.iaea.org/Publications/Booklets/Chernobyl/chernobyl.pdf]
32. an increase in thyroid cancer: For a recent follow-up see Alina V. Brenner et al., “I-131 Dose Response for Incident Thyroid Cancers in Ukraine Related to the Chernobyl Accident,” Environmental Health Perspectives 119, no. 7 (July 2011): 933–39. [http://www.ncbi.nlm.nih.gov/pubmed/21406336]
33. the biggest public health problem … has been psychological: “Chernobyl’s Legacy,” 36.
34. “a paralyzing fatalism”: Elisabeth Rosenthal, “Experts Find Reduced Effects of Chernobyl,” New York Times, September 6, 2005. [http://www.nytimes.com/2005/09/06/international/europe/06chernobyl.html]
35. recently opened the Chernobyl site to tourism: Peter Walker, “Chernobyl: Now Open to Tourists,” The Guardian, December 13, 2010. [http://www.guardian.co.uk/world/2010/dec/13/chernobyl-now-open-to-tourists]
36. a mecca for wildlife: Robert J. Baker and Ronald K. Chesser, “The Chernobyl Nuclear Disaster and Subsequent Creation of a Wildlife Preserve,” Environmental Toxicology and Chemistry 19, no. 5 (May 1, 2000): 1231–32. [http://www.nsrl.ttu.edu/chornobyl/wildlifepreserve.htm]
37. killed at least 150,000 people: “How Many People Died as a Result of the Atomic Bombings?” Radiation Effects Research Foundation website. [http://www.rerf.or.jp/general/qa_e/qa1.html]
38. 527 excess deaths from solid cancers: Kotaro Ozasa et al., “Studies of the Mortality of Atomic Bomb Survivors, Report 14, 1950–2003: An Overview of Cancer and Noncancer Diseases,” Radiation Research 177, no. 3 (March 2012): 229–43. [http://www.ncbi.nlm.nih.gov/pubmed/22171960]
39. and 103 from leukemias: David Richardson et al., “Ionizing Radiation and Leukemia Mortality Among Japanese Atomic Bomb Survivors, 1950–2000,” Radiation Research 172, no. 3 (September 2009): 368–82. [http://www.ncbi.nlm.nih.gov/pubmed/19708786] Using incidence instead of mortality figures, the Radiation Effects Research Foundation attributed 1,900 cases of cancer to the bombs. See “How Many Cancers in Atomic-bomb Survivors are Attributable to Radiation?” on the foundation’s website. [http://www.rerf.or.jp/general/qa_e/qa2.html]
40. Tsutomu Yamaguchi survived both blasts: Mark McDonald, “Tsutomu Yamaguchi, Survivor of 2 Atomic Blasts, Dies at 93,” New York Times, January 7, 2010. [http://www.nytimes.com/2010/01/07/world/asia/07yamaguchi.html]
41. “cancer in a molten, liquid form”: Siddhartha Mukherjee, The Emperor of All Maladies: A Biography of Cancer (New York: Scribner, 2010), 16.
42. reburied with Pierre in the Panthéon: Nanny Fröman, “Marie and Pierre Curie and the Discovery of Polonium and Radium,” December 1, 1996, Nobel Prize website. [http://www.nobelprize.org/nobel_prizes/physics/articles/curie]
43. worried that her body would be dangerously radioactive: D. Butler, “X-rays, Not Radium, May Have Killed Curie,” Nature 377, no. 6545 (September 14, 1995): 96. [http://www.ncbi.nlm.nih.gov/pubmed/7675094]
44. kept in a lead box at the Bibliothèque Nationale: Fröman, “Marie and Pierre Curie.”
45. too ill to travel to Stockholm: Marie Curie, Pierre Curie (With the Autobiographical Notes of Marie Curie), trans. Charlotte Kellogg (New York: Macmillan Co., 1923), 125. [http://etext.virginia.edu/toc/modeng/public/CurPier.html]
46. Pierre described an experiment: “Radioactive Substances, Especially Radium,” June 6, 1905, in Nobel Lectures, Physics 1901–1921 (Amsterdam: Elsevier Publishing Company, 1967). Available on the Nobel Prize website. [http://www.nobelprize.org/nobel_prizes/physics/laureates/1903/pierre-curie-lecture.html]
47. A targeted drug called Alpharadin: Christopher Parker et al., “Overall Survival Benefit of Radium-223 Chloride (Alpharadin) in the Treatment of Patients with Symptomatic Bone Metastases in Castration-Resistant Prostate Cancer,” 7th NCRI Cancer Conference, November 2011, Liverpool. [http://www.ncri.org.uk/ncriconference/2011abstracts/abstracts/ClinicalShowcase1.html] Also see Deborah A. Mulford, David A. Scheinberg, and Joseph G. Jurcic, “The Promise of Targeted Alpha-particle Therapy,” Journal of Nuclear Medicine 46 suppl. 1 (January 2005): 199S–204S. [http://www.ncbi.nlm.nih.gov/pubmed/15653670]
CHAPTER 12 The Immortal Demon
1. “Kisses for the Cure”: Anne Landman, “How Breast Cancer Became Big Business,” PR Watch website, June 14, 2008. [http://www.prwatch.org/node/7436]
2. Stand Up to Cancer telethon: “The Show,” Stand Up to Cancer website. [http://standup2cancer.org/theshow] (There has since been a 2012 broadcast.)
3. a workshop that evening at the Parker House: “Translational Cancer Research for Basic Scientists Workshop,” American Association for Cancer Research, October 17–22, 2010, Boston, MA.
4. told the story of two cousins: Amy Harmon, “New Drugs Stir Debate on Rules of Clinical Trials,” New York Times, September 18, 2010. [http://www.nytimes.com/2010/09/19/health/research/19trial.html] For more about the trial see Amy Harmon, “Target Cancer,” a series of six articles, New York Times, February 22, 2010, to January 20, 2011. [http://topics.nytimes.com/top/news/health/series/target_cancer/index.html]
5. a mutation in a gene called BRAF: As a result, the gene produces a distorted version of a protein that is part of a cellular growth pathway. Normally the BRAF protein is actuated only when it interacts with another protein called RAS, but the mutation frees it of this constraint. See “Vemurafenib,” New Treatments, Melanoma Foundation website. [http://www.melanoma.org.nz/About-Melanoma/Diagnosis-and-Treatment/New-Treatments/Vemurafenib] For a description of the cancer and the vemurafenib trials see Paul B. Chapman et al., “Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation,” New England Journal of Medicine 364, no. 26 (June 30, 2011): 2507–16. [http://www.nejm.org/doi/full/10.1056/NEJMoa1103782] For a later study see Jeffrey A. Sosman et al., “Survival in BRAF V600-Mutant Advanced Melanoma Treated with Vemurafenib,” New England Journal of Medicine 366, no. 8 (2012): 707–14. [http://www.nejm.org/doi/full/10.1056/NEJMoa1112302]
6. Phase III proved so definitive: Andrew Pollack, “Two New Drugs Show Promise in Slowing Advanced Melanoma,” New York Times, June 6, 2011. [http://www.nytimes.com/2011/06/06/health/research/06melanoma.html]
7. typically living four months longer: The median overall survival was 13.2 vs. 9.6 months for dacarbazine. See Paul B. Chapman et al., “Updated Overall Survival (OS) Results for BRIM-3,” 2012 ASCO Annual Meeting, Journal of Clinical Oncology 30 no. 18, suppl. (June 20, 2012): abstract 8502. [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=114&abstractID=97795]
8. sixty-six in the dacarbazine group: “Clinical Trial Result Information,” protocol number NO25026, January 4, 2011, Roche trials database website. [http://www.roche-trials.com/studyResultGet.action?studyResultNumber=NO25026]
9. half of the people … were dead: Chapman, “Updated Overall Survival (OS) Results.”
10. “he was running a race”: Alexander Solzhenitsyn, Cancer Ward, trans. Nicholas Bethell and David Burg (New York: Farrar, Straus and Giroux, 1969), 250.
11. through a fortuitous mutation: Ramin Nazarian et al., “Melanomas Acquire Resistance to B-RAF(V600E) Inhibition by RTK or N-RAS Upregulation,” Nature 468, no. 7326 (November 24, 2010): 973–77. [http://www.nature.com/nature/journal/v468/n7326/abs/nature09626.html]
12. a paradoxical side effect: Fei Su et al., “RAS Mutations in Cutaneous Squamous-cell Carcinomas in Patients Treated with BRAF Inhibitors,” New England Journal of Medicine 366, no. 3 (January 19, 2012): 207–15. [http://www.nejm.org/doi/full/10.1056/NEJMoa1105358]
13. experimenting with combinations: In 2012, The New
England Journal of Medicine reported encouraging results from a trial involving dabrafenib, a different BRAF inhibitor. It was combined with trametinib, which inhibits MEK, another enzyme in the same cellular pathway. See Keith T. Flaherty et al., “Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations,” New England Journal of Medicine (published online September 29, 2012). [http://www.nature.com/nature/journal/v468/n7326/abs/nature09626.html]
14. described the jarring effect: Tom Curran, “Oncology as a Team Sport,” Translational Cancer Research Workshop, October 17, 2010.
15. discovered a gene called reelin: G. D’Arcangelo, T. Curran, et al., “A Protein Related to Extracellular Matrix Proteins Deleted in the Mouse Mutant Reeler,” Nature 374, no. 6524 (April 20, 1995): 719–23; [http://www.ncbi.nlm.nih.gov/pubmed/7715726] and G. G. Miao, T. Curran, et al., “Isolation of an Allele of Reeler by Insertional Mutagenesis,” Proceedings of the National Academy of Sciences 91, no. 23 (November 8, 1994): 11050–54. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC45164]
16. 8 cases in 10 million: Betsy A. Kohler et al., “Annual Report to the Nation on the Status of Cancer, 1975–2007, Featuring Tumors of the Brain and Other Nervous System,” Journal of the National Cancer Institute 103, no. 9 (May 4, 2011), 1–23, table 5.
17. 5 cases per 100,000 among children: Kohler et al., “Annual Report,” 12, table 6.
18. the most common pediatric brain tumor: Charles M. Rudin et al., “Treatment of Medulloblastoma with Hedgehog Pathway Inhibitor GDC-0449,” New England Journal of Medicine 361, no. 12 (September 17, 2009): 1173–78. [http://www.nejm.org/doi/full/10.1056/NEJMoa0902903#t=abstract]
19. median age of diagnosis is five: Rudin, “Treatment of Medulloblastoma.”
20. “a clumsy, staggered walking pattern”: “Medulloblastoma,” American Brain Tumor Association website (2006), 6. [http://www.abta.org/understanding-brain-tumors/types-of-tumors/medulloblastoma.html]
The Cancer Chronicles Page 31