The Cancer Chronicles
Page 23
45. Scientists have proposed several reasons: See, for example, Anders Bredberg, “Cancer Resistance and Peto’s Paradox,” Proceedings of the National Academy of Sciences 106, no. 20 (May 19, 2009): E51; [http://www.pnas.org/content/106/20/E51.short] and George Klein, “Reply to Bredberg: The Voice of the Whale,” on page E52. [http://www.pnas.org/content/106/20/E52.short]
46. hypertumors: Nagy, Victor, and Cropper, “Why Don’t All Whales Have Cancer?”
47. thought there must be some kind of connection: F. Galis, “Why Do Almost All Mammals Have Seven Cervical Vertebrae? Developmental Constraints, Hox Genes, and Cancer,” The Journal of Experimental Zoology 285, no. 1 (April 15, 1999): 19–26. [http://www.ncbi.nlm.nih.gov/pubmed/10327647]
48. “Natural Compounds in Pomegranates”: These titles are from AACR press releases, American Association for Cancer Research website. [http://www.aacr.org/home/public-media.aspx]
CHAPTER 2 Nancy’s Story
1. two-thirds of cancer cases are preventable: See, for example, World Cancer Research Fund/American Institute for Cancer Research, Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective (Washington, DC: AICR, 2007), xxv. [http://www.dietandcancerreport.org]
2. the argument is weak at best: Miguel A. Sanjoaquin et al., “Folate Intake and Colorectal Cancer Risk: A Meta-analytical Approach,” International Journal of Cancer 113, no. 5 (February 20, 2005): 825–28 [http://www.ncbi.nlm.nih.gov/pubmed/15499620]; Susanna C. Larsson, Edward Giovannucci, and Alicja Wolk, “Folate and Risk of Breast Cancer: A Meta-analysis,” Journal of the National Cancer Institute 99, no. 1 (January 3, 2007): 64–76 [http://jnci.oxfordjournals.org/content/99/1/64.abstract]; and Jane C. Figueiredo et al., “Folic Acid and Risk of Prostate Cancer: Results from a Randomized Clinical Trial,” Journal of the National Cancer Institute 101, no. 6 (March 18, 2009): 432–35. [http://jnci.oxfordjournals.org/content/101/6/432.short]
3. folic acid … can increase cancer risk: See, for example, Figueiredo et al., “Folic Acid and Risk of Prostate Cancer”; and Marta Ebbing et al., “Cancer Incidence and Mortality After Treatment with Folic Acid and Vitamin B12,” JAMA: The Journal of the American Medical Association 302, no. 19 (November 18, 2009): 2119–26. [http://www.ncbi.nlm.nih.gov/pubmed/19920236]
4. administering antifolates: John J. McGuire, “Anticancer Antifolates: Current Status and Future Directions,” Current Pharmaceutical Design 9, no. 31 (2003): 2593–613. [http://www.ncbi.nlm.nih.gov/pubmed/14529544]
5. among the oldest chemotherapeutic drugs: The pioneer in this research was Sidney Farber. See S. Farber et al., “Temporary Remissions in Acute Leukemia in Children Produced by Folic Acid Antagonist, 4-Aminopteroyl-Glutamic Acid,” New England Journal of Medicine 238, no. 23 (June 3, 1948): 787–93. [http://www.nejm.org/doi/full/10.1056/NEJM194806032382301] The story is told in Siddhartha Mukherjee’s fine book The Emperor of All Maladies: A Biography of Cancer (New York: Scribner, 2010), 27–36.
6. the mythology surrounding antioxidants: Rudolf I. Salganik, “The Benefits and Hazards of Antioxidants,” Journal of the American College of Nutrition 20 (2001): 464S–72S. [http://www.ncbi.nlm.nih.gov/pubmed/11603657]
7. a clinical trial in Finland: “The Effect of Vitamin E and Beta Carotene on the Incidence of Lung Cancer and Other Cancers in Male Smokers,” New England Journal of Medicine 330, no. 15 (April 14, 1994): 1029–35. [http://www.ncbi.nlm.nih.gov/pubmed/8127329]
8. A similar trial in the United States: Gary E. Goodman et al., “The Beta-Carotene and Retinol Efficacy Trial,” Journal of the National Cancer Institute 96, no. 23 (December 1, 2004): 1743–50. [http://www.ncbi.nlm.nih.gov/pubmed/15572756]
9. phytochemicals: Lee W. Wattenberg, “Chemoprophylaxis of Carcinogenesis: A Review,” part 1, Cancer Research 26, no. 7 (July 1, 1966): 1520–26. [http://cancerres.aacrjournals.org/content/26/7_Part_1/1520.abstract]
10. the evidence here is also meager: A randomized controlled study of male doctors recently reported an annual cancer incidence of 1.7 percent among the multivitamin takers compared with 1.8 percent for the placebo group: J. Gaziano et al., “Multivitamins in the Prevention of Cancer in Men,” JAMA: The Journal of the American Medical Association (published online October 17, 2012): 1–10. See the comment section of the paper for references to other studies finding neutral and even negative effects.
11. 5 A Day program: “5 A Day for Better Health Program Evaluation Report: Executive Summary,” National Cancer Institute website, last updated March 1, 2006. [http://dccps.nci.nih.gov/5ad_exec.html]
12. The evidence, alas: Walter C. Willett, “Fruits, Vegetables, and Cancer Prevention: Turmoil in the Produce Section,” Journal of the National Cancer Institute 102, no. 8 (April 21, 2010): 510–11. [http://jnci.oxfordjournals.org/content/102/8/510.short]
13. those most likely to volunteer: Willett, “Fruits, Vegetables, and Cancer Prevention.”
14. The largest prospective study on diet and health: The European Prospective Investigation into Cancer and Nutrition, or EPIC, is described on the website of the International Agency for Research on Cancer. [http://epic.iarc.fr] For a summary with citations of key EPIC findings, see “Diet and Cancer: the Evidence,” Cancer Research UK website, [http://info.cancerresearchuk.org/healthyliving/dietandhealthyeating/howdoweknow] updated September 25, 2009.
15. a very weak effect: Willett, “Fruits, Vegetables, and Cancer Prevention”; and Paolo Boffetta et al., “Fruit and Vegetable Intake and Overall Cancer Risk in the European Prospective Investigation into Cancer and Nutrition,” Journal of the National Cancer Institute 102, no. 8 (April 21, 2010): 529–37. [http://www.ncbi.nlm.nih.gov/pubmed/20371762, http://jnci.oxfordjournals.org/content/early/2010/04/06/jnci.djq072] No evidence was found that fruits and vegetables help ward off cancer of the breast (Carla H. van Gils et al., “Consumption of Vegetables and Fruits and Risk of Breast Cancer,” JAMA: The Journal of the American Medical Association 293, no. 2 [January 12, 2005]: 183–93) [http://jama.ama-assn.org/content/293/2/183.abstract] or cancer of the prostate (Timothy J. Key et al., “Fruits and Vegetables and Prostate Cancer,” International Journal of Cancer 109, no. 1 [March 2004]: 119–24). [http://www.ncbi.nlm.nih.gov/pubmed/14735477]
16. possible benefits with a few cancers: See, for example, Anthony B. Miller et al., “Fruits and Vegetables and Lung Cancer,” International Journal of Cancer 108, no. 2 (January 10, 2004): 269–76 [http://www.ncbi.nlm.nih.gov/pubmed/14639614]; and Heiner Boeing et al., “Intake of Fruits and Vegetables and Risk of Cancer of the Upper Aero-digestive Tract,” Cancer Causes & Control 17, no. 7 (September 2006): 957–69. [http://www.ncbi.nlm.nih.gov/pubmed/16841263]
17. said to nurture a mix of bacteria: Constantine Iosif Fotiadis et al., “Role of Probiotics, Prebiotics and Synbiotics in Chemoprevention for Colorectal Cancer,” World Journal of Gastroenterology 14, no. 42 (November 14, 2008): 6453–57 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773329]; and Janelle C. Arthur and Christian Jobin, “The Struggle Within: Microbial Influences on Colorectal Cancer,” Inflammatory Bowel Diseases 17, no. 1 (January 2011): 396–409. [http://www.ncbi.nlm.nih.gov/pubmed/20848537]
18. The case for fiber may be a little stronger: See Teresa Norat et al., “The Associations Between Food, Nutrition and Physical Activity and the Risk of Colorectal Cancer,” which is available along with other recent EPIC findings on the World Cancer Research Fund’s Diet and Cancer Report website. [http://www.dietandcancerreport.org/cancer_resource_center/continuous_update_project.php] See “Continuous Update Project Report Summary. Food, Nutrition, Physical Activity, and the Prevention of Colorectal Cancer” (2011).
19. the evidence has been controversial: EPIC’s positive findings were published as Sheila A. Bingham et al., “Dietary Fibre in Food and Protection Against Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition,” Lancet 361, no. 9368 (May 3, 2003): 1496–1501. [http://www.ncbi.nlm.nih.gov/pubmed/12737858] For conflicting results from the Nurses’ Health Study, see Scott Gott
lieb, “Fibre Does Not Protect Against Colon Cancer,” BMJ: British Medical Journal 318, no. 7179 (January 30, 1999): 281; and C. S. Fuchs, W. C. Willett, et al., “Dietary Fiber and the Risk of Colorectal Cancer and Adenoma in Women,” New England Journal of Medicine 340, no. 3 (January 21, 1999): 169–76. [http://www.ncbi.nlm.nih.gov/pubmed/9895396]
20. no evidence of a reduction in colorectal polyps: Arthur Schatzkin et al., “Lack of Effect of a Low-Fat, High-Fiber Diet on the Recurrence of Colorectal Adenomas,” New England Journal of Medicine 342, no. 16 (April 20, 2000): 1149–55. [http://www.nejm.org/doi/full/10.1056/nejm200004203421601#t=abstract] Similar controlled studies have also found no relationship. See, for example, D. S. Alberts et al., “Lack of Effect of a High-fiber Cereal Supplement on the Recurrence of Colorectal Adenomas,” New England Journal of Medicine 342, no. 16 (April 20, 2000): 1156–62; and Shirley A. Beresford et al., “Low-fat Dietary Pattern and Risk of Colorectal Cancer,” JAMA: The Journal of the American Medical Association 295, no. 6 (February 8, 2006): 643–54.
21. no effect on the recurrence of breast cancer: John P. Pierce et al., “Influence of a Diet Very High in Vegetables, Fruit, and Fiber and Low in Fat on Prognosis Following Treatment for Breast Cancer,” JAMA: The Journal of the American Medical Association 298, no. 3 (July 18, 2007): 289–98. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2083253]
22. brussels sprouts, cabbage: B. N. Ames, M. Profet, and L. S. Gold, “Nature’s Chemicals and Synthetic Chemicals: Comparative Toxicology,” Proceedings of the National Academy of Sciences 87, no. 19 (October 1990): 7782–86 [http://www.pnas.org/content/87/19/7782.abstract] and Bruce N. Ames, “Dietary Carcinogens and Anticarcinogens,” Science 221, no. 4617 (September 23, 1983): 1256–64. [http://www.ncbi.nlm.nih.gov/pubmed/6351251]
23. eating a lot of red meat: The calculation is for a fifty-year-old. See Teresa Norat et al., “Meat, Fish, and Colorectal Cancer Risk,” Journal of the National Cancer Institute 97, no. 12 (June 15, 2005): 906–16; [http://www.ncbi.nlm.nih.gov/pubmed/15956652] and Doris S. M. Chan et al., “Red and Processed Meat and Colorectal Cancer Incidence: Meta-Analysis of Prospective Studies,” PLOS ONE 6, no. 6 (June 6, 2011). [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108955]
24. from 1.28 percent to 1.7 percent: Norat et al., “Meat, Fish, and Colorectal Cancer Risk.”
25. fish, fish oils, and colon cancer prevention: For evidence that eating fish discourages cancer by encouraging apoptosis and impeding cellular proliferation, see Youngmi Cho et al., “A Chemoprotective Fish Oil- and Pectin-Containing Diet Temporally Alters Gene Expression Profiles in Exfoliated Rat Colonocytes Throughout Oncogenesis,” Journal of Nutrition 141, no. 6 (June 1, 2011): 1029–35. [http://jn.nutrition.org/content/141/6/1029.abstract] For another perspective, see Catherine H. MacLean et al., “Effects of Omega-3 Fatty Acids on Cancer Risk,” JAMA: The Journal of the American Medical Association 295, no. 4 (January 25, 2006): 403–15. [http://www.ncbi.nlm.nih.gov/pubmed/16434631]
26. mammalian fat … has come under challenge: Ross L. Prentice et al., “Low-Fat Dietary Pattern and Risk of Invasive Breast Cancer: The Women’s Health Initiative Randomized Controlled Dietary Modification Trial,” JAMA: The Journal of the American Medical Association 295, no. 6 (February 8, 2006): 629–42; [http://jama.ama-assn.org/content/295/6/629] and Shirley A. Beresford et al., “Low-Fat Dietary Pattern and Risk of Colorectal Cancer.” For a summary, see “The Nutrition Source: Low-Fat Diet Not a Cure-All,” Harvard School of Public Health website. [http://www.hsph.harvard.edu/nutritionsource/nutrition-news/low-fat]
27. sugar may pose a greater danger: Gary Taubes, Good Calories, Bad Calories: Fats, Carbs, and the Controversial Science of Diet and Health (New York: Vintage, 2008); and Gary Taubes, Why We Get Fat: And What to Do About It (New York: Knopf, 2010).
28. Obesity … has joined the short list: See, for example, “AACR Cancer Progress Report,” 2012, American Association for Cancer Research website. [http://cancerprogressreport.org]
29. caloric restriction: The mechanisms are complex, involving insulin regulation and other cellular processes. See Stephen D. Hursting et al., “Calorie Restriction, Aging, and Cancer Prevention,” Annual Review of Medicine 54 (February 2003): 131–52 [http://www.annualreviews.org/doi/abs/10.1146/annurev.med.54.101601.152156]; D. Kritchevsky, “Caloric Restriction and Cancer,” Journal of Nutritional Science and Vitaminology 47, no. 1 (February 2001): 13–19 [http://www.ncbi.nlm.nih.gov/pubmed/11349885]; Sjoerd G. Elias et al., “Transient Caloric Restriction and Cancer Risk (The Netherlands),” Cancer Causes & Control 18, no. 1 (February 2007): 1–5 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1764866]; and David M. Klurfeld et al., “Reduction of Enhanced Mammary Carcinogenesis in LA/N-cp (Corpulent) Rats by Energy Restriction,” Proceedings of the Society for Experimental Biology and Medicine 196, no. 4 (April 1, 1991): 381–84. [http://ebm.rsmjournals.com/content/196/4/381.abstract] In Good Calories, Bad Calories Taubes argues that the anticarcinogenic effects seen in the animal experiments come not from an overall reduction in calories but from limiting sugars and carbohydrates.
30. a jolt of estrogen: See, for example, Endogenous Hormones and Breast Cancer Collaborative Group, “Circulating Sex Hormones and Breast Cancer Risk Factors in Postmenopausal Women,” British Journal of Cancer 105, no. 5 (2011): 709–22 [http://dx.doi.org/10.1038/bjc.2011.254]; A. Heather Eliassen et al., “Endogenous Steroid Hormone Concentrations and Risk of Breast Cancer Among Premenopausal Women,” Journal of the National Cancer Institute 98, no. 19 (October 4, 2006): 1406–15 [http://jnci.oxfordjournals.org/content/98/19/1406.abstract]; and Rudolf Kaaks et al., “Serum Sex Steroids in Premenopausal Women and Breast Cancer Risk,” Journal of the National Cancer Institute 97, no. 10 (May 18, 2005): 755–65. [http://jnci.oxfordjournals.org/content/97/10/755.abstract]
31. the list of known human carcinogens: National Toxicology Program, Report on Carcinogens, 12th ed. (Research Triangle Park, NC: U.S. Department of Health and Human Services, 2011). Available on the National Toxicology Program website. [http://ntp-server.niehs.nih.gov/?objectid=03C9AF75-E1BF-FF40-DBA9EC0928DF8B15]
32. possibly increasing the risk of breast cancer: See, for example, F. Clavel-Chapelon, “Differential Effects of Reproductive Factors on the Risk of Pre- and Postmenopausal Breast Cancer,” British Journal of Cancer 86, no. 5 (March 4, 2002): 723–27. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2230628]
33. A few scientists blame the change on bisphenol A: See, for example, Kembra L. Howdeshell et al., “Environmental Toxins: Exposure to Bisphenol A Advances Puberty,” Nature 401, no. 6755 (October 21, 1999): 763–64 [http://www.nature.com/nature/journal/v401/n6755/full/401763a0.html]; and Laura N. Vandenberg, Ana M. Soto, et al., “Bisphenol-A and the Great Divide: A Review of Controversies in the Field of Endocrine Disruption,” Endocrine Reviews 30, no. 1 (February 1, 2009): 75–95. [http://edrv.endojournals.org/content/30/1/75.abstract]
34. a more widely accepted explanation involves nutrition: See Sandra Steingraber, “The Falling Age of Puberty in U.S. Girls,” August 2007, Breast Cancer Fund website, [http://www.breastcancerfund.org/media/publications/falling-age-of-puberty] which includes citations to the research; and Sarah E. Anderson, Gerard E. Dallal, and Aviva Must, “Relative Weight and Race Influence Average Age at Menarche,” part 1, Pediatrics 111, no. 4 (April 2003): 844–50. [http://www.ncbi.nlm.nih.gov/pubmed/12671122]
35. the age of menarche … has dropped: Steingraber, “The Falling Age of Puberty,” 20.
36. Lactation also appears to hold estrogen in check: See World Cancer Research Fund/American Institute for Cancer Research, Food, Nutrition, Physical Activity, and the Prevention of Cancer, 239–42.
37. more menstrual cycles than her grandmother: David Plotkin, “Good News and Bad News About Breast Cancer,” The Atlantic, June 1998. [http://www.theatlantic.com/magazine/archive/1998/06/good-news-and-bad-news-about-breast-cancer/5504]
38. Hormone therapies … associated with some cancers: For an overview see two reports on the National
Cancer Institute website “Menopausal Hormone Therapy and Cancer” [http://www.cancer.gov/cancertopics/factsheet/Risk/DES] and “Diethylstilbestrol (DES) and Cancer,” both reviewed December 5, 2011. [http://www.cancer.gov/cancertopics/factsheet/Risk/menopausal-hormones]
39. obesity, especially in older women: Sabina Rinaldi et al., “Anthropometric Measures, Endogenous Sex Steroids and Breast Cancer Risk in Postmenopausal Women,” International Journal of Cancer 118, no. 11 (June 1, 2006): 2832–39 [http://www.ncbi.nlm.nih.gov/pubmed/16385576]; and Petra H. Lahmann et al., “A Prospective Study of Adiposity and Postmenopausal Breast Cancer Risk,” International Journal of Cancer 103, no. 2 (November 4, 2002): 246–52. [http://onlinelibrary.wiley.com/doi/10.1002/ijc.10799/abstract]
40. reduce the chances of premenopausal women getting breast cancer: Kaaks et al., “Serum Sex Steroids in Premenopausal Women and Breast Cancer Risk.” Also see Elisabete Weiderpass et al., “A Prospective Study of Body Size in Different Periods of Life and Risk of Premenopausal Breast Cancer,” Cancer Epidemiology, Biomarkers & Prevention 13, no. 7 (July 2004): 1121–27; and L. J. Vatten and S. Kvinnsland, “Prospective Study of Height, Body Mass Index and Risk of Breast Cancer,” Acta Oncologica 31, no. 2 (1992): 195–200. [http://www.ncbi.nlm.nih.gov/pubmed/1622634]
41. oral contraceptives may slightly raise the odds: “Oral Contraceptives and Cancer Risk,” National Cancer Institute, reviewed March 21, 2012.
42. Alcohol … with digestive cancers: The evidence for esophageal, liver, and other cancers is examined in Vincenzo Bagnardi et al., “Alcohol Consumption and the Risk of Cancer: A Meta-Analysis,” Alcohol Research and Health: The Journal of the National Institute on Alcohol Abuse and Alcoholism 25, no. 4 (2001): 263–70. [http://pubs.niaaa.nih.gov/publications/arh25-4/263-270.htm]