Blood Matters

by Masha Gessen

  Studies of the effects of surgical menopause: A. K. Farrag, E. M. Khedr, H. Abdel-Aleem, T. A. Rageh, “Effect of surgical menopause on cognitive functions,” Dementia and Geriatric Cognitive Disorders, March 2002, 193–198; R. E. Nappi, E. Sinforiani, M. Mauri, G. Bono, F. Polatti, G. Nappi, “Memory functioning at menopause: Impact of age in ovariectomized women,” Gynecologic and Obstetric Investigation 47 (January 1999): 29–36; D. Kritz-Silverstein, E. Barrett-Connor, “Hysterectomy, oophorectomy, and cognitive function in older women,” Journal of the American Geriatric Society 50 (January 2002): 55–61.

  Studies of additional markers of ovarian cancer: J. O. Schorge, R. D. Drake, H. Lee, S. J. Skates, R. Rajanbabu, D. S. Miller, J. H. Kim, D. W. Cramer, R. S. Berkowitz, S. C. Mok, “Osteopontin as an adjunct to CA125 in detecting recurrent ovarian cancer,” Clinical Cancer Research 10 (May 2004): 3474–3478; B. Ye, D. W. Cramer, S. J. Skates, S. P. Gygi, V. Pratomo, L. Fu, N. K. Horick, L. J. Licklider, J. O. Schorge, R. S. Berkowitz, S. C. Mok, “Haptoglobin-alpha subunit as potential serum biomarker in ovarian cancer: Identification and characterization using proteomic profiling and mass spectrometry,” Clinical Cancer Research 9 (August 2003): 2904–2911; S. C. Mok, J. Chao, S. Skates, K. Wong, G. K. Yiu, M. G. Muto, R. S. Berkowitz, D. W. Cramer, “Prostasin, a potential serum marker for ovarian cancer: Identification through microarray technology,” Journal of the National Cancer Institute 93 (October 2001): 1458–1464.

  Intersex conditions and varying views on the treatment of intersex babies are described on the Web site of the Intersex Society of North America, http://www.isna.org/faq/ conditions (accessed September 13, 2007). Approaches to the treatment of intersex babies are described in Alice Domurat Dreger, “Ambiguous Sex—or Ambivalent Medicine?” Hastings Center Report 28 (May/June 1998): 24–35.

  The paper that shattered the myth of David Reimer’s successful sex reassignment: Milton Diamond, H. Keith Sigmundson, “Sex reassignment at birth: A long term review and clinical implications,” Archives of Pediatric & Adolescent Medicine 151 (March 1997): 298–304.

  For a discussion of once-routine unnecessary surgeries see Thomas B. Freeman, Dorothy E. Vawter, Paul E. Leaverton, James H. Godbold, Robert A. Hauser, Christopher G. Goetz, MD, C. Warren Olanow, MD, “Use of placebo surgery in controlled trials of a cellular-based therapy for Parkinson’s disease,” New England Journal of Medicine 151 (September 23, 1999): 988–992.

  Prognosis for mutation carriers who have cancer: M. E. Robson, P. O. Chappuis, J. Satagopan, N. Wong, J. Boyd, J. R. Goffin, C. Hudis, D. Roberge, L. Norton, L. R. Bégin, K. Offit, W. D. Foulkes, “A combined analysis of outcome following breast cancer: Differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment,” Breast Cancer Research 6 (October 2003): R8–R17; Ilana Cass, Rae Lynn Baldwin, Taz Varkey, Roxana Moslehi, Steven A. Narod, Beth Y. Karlan, “Improved survival in women with BRCA-associated ovarian carcinoma,” Cancer 97 (May 2003): 2187–2195; John R. Goffin, Pierre O. Chappuis, Louis R. Bégin, Nora Wong, Jean-Sébastien Brunet, Nancy Hamel, Ann-Josée Paradis, Jeff Boyd, William D. Foulkes, “Impact of germline BRCA1 mutations and overexpression of p53 on prognosis and response to treatment following breast carcinoma,” Cancer 97 (February 2003): 527–536; Pål Møller, Åke Borg, D. Gareth Evans, Neva Haites, Marta M. Reis, Hans Vasen, Elaine Anderson, C. Michael Steel, Jaran Apold, David Goudie, Anthony Howell, Fiona Lalloo, Lovise Mæhle, Helen Gregory, Ketil Heimdal, “Survival in prospectively ascertained familial breast cancer: Analysis of a series stratified by tumour characteristics, BRCA mutations and oophorectomy,” International Journal of Cancer 101 (October 20, 2002): 555–559; Y. Ben David, A. Chetrit, G. Hirsh-Yechezkel, E. Friedman, B. D. Beck, U. Beller, G. Ben-Baruch, A. Fishman, H. Levavi, F. Lubin, J. Menczer, B. Piura, J. P. Struewing, B. Modan for the National Israeli Study of Ovarian Cancer, “Effect of BRCA mutations on the length of survival in epithelial ovarian tumors,” Journal of Clinical Oncology 20 (January 2002): 463–466; Lori J. Pierce, Myla Strawderman, Steven A. Narod, Ivo Oliviotto, Andrea Eisen, Laura Dawson, David Gaffney, Lawrence J. Solin, Asa Nixon, Judy Garber, Christine Berg, Claudine Isaacs, Ruth Heimann, Olufunmilayo I. Olopade, Bruce Haffty, Barbara L. Weber, “Effect of radiotherapy after breast-conserving treatment in women with breast cancer and germline BRCA1/2 mutations,” Journal of Clinical Oncology 18 (October 2000): 3360–3369.

  Mutation carriers behavior study: Jeffrey R. Botkin, Ken R. Smith, Bonnie J. Baty, Jean E. Wylie, Debra Dutson, Anna Chan, Heidi A. Hamann, Caryn Lerman, Jamie McDonald, Vickie Venne, John H. Ward, Elaine Lyon, “Genetic testing for a BRCA mutation: Prophylactic surgery and screening behavior in women 2 years post testing,” American Journal of Medical Genetics Part A 118A (March 2003): 201–209.

  On male breast cancer and genetics: J. R. Weiss, K. B. Moysich, H. Swede, “Epidemiology of male breast cancer,” Cancer Epidemiology Biomarkers & Prevention 14 (January 2005): 20–26; A. Joseph, K. Mokbel, “Male breast cancer,” International Journal of Fertility and Women’s Medicine 49 (September—October 2004): 198–199; K. Syrjäkoski, T. Kuukasjarvi, K. Waltering, K. Haraldsson, A. Auvinen, A. Borg, T. Kainu, O.-P. Kallioniemi, P. A. Koivisto, “BRCA2 mutations in 154 Finnish male breast cancer patients,” Neoplasia 6 (September—October 2004): 541–545.

  On exercise and diet as modifiers of cancer risk: A. McTiernan, “Behavioral risk factors in breast cancer: Can risk be modified?” Oncologist 8 (August 2003): 326–334.

  On risk perception: David Ropeik, George Gray, Risk: A Practical Guide for Deciding What’s Really Safe and What’s Really Dangerous in the World Around You (Boston: Houghton Mifflin, 2002).

  On women’s perceptions of breast cancer risk: N. Humpel, S. C. Jones, “‘I don’t really know, so it’s a guess’: Women’s reasons for breast cancer risk estimation,” Asian Pacific Journal of Cancer Prevention 5 (October—December 2004): 428–432; S. Davis, S. Stewart, J. Bloom, “Increasing the accuracy of perceived breast cancer risk: Results from a randomized trial with Cancer Information Service callers,” Preventive Medicine 39 (July 2004): 64–73.

  CHAPTER 6: THE FATHER OF HEREDITARY CANCERS

  Aldred Scott Warthin and Lynch syndrome: A. G. Thorson, J. A. Knezetic, H. T. Lynch, “A century of progress in hereditary nonpolyposis colorectal cancer (Lynch syndrome),” Diseases of the Colon and Rectum 42 (January 1999): 1–9; Henry T. Lynch, Thomas Smyrk, Jane F. Lynch, “Molecular genetics and clinical-pathology features of hereditary nonpolyposis colorectal carcinoma (Lynch syndrome): Historical journey from pedigree anecdote to molecular genetic confirmation,” Oncology 55 (March—April 1998): 103–108; H. T. Lynch, T. C. Smyrk, P. Watson, S. J. Lanspa, J. F. Lynch, P. M. Lynch, R. J. Cavalieri, C. R. Boland, “Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: An updated review,” Gastroenterology 104 (May 1993): 1535–1549.

  Dr. Lynch’s search for genetic clues: H. T. Lynch, R. J. Thomas, H. A. Gurgis, J. Lynch, “Clues to cancer risk: Biologic markers,” American Family Physician 11 (March 1975): 153–158; H. T. Lynch, R. J. Thomas, P. I. Terasaki, A. Ting, H. A. Guirgis, A. R. Kaplan, H. Magee, J. Lynch, C. Kraft, E. Chaperon, “HL-A in cancer family ‘N,’” Cancer 36 (October 1975): 1315–1320; M. C. King, R. C. Go, H. T. Lynch, R. C. Elston, P. I. Terasaki, N. L. Petrakis, G. C. Rodgers, D. Lattanzio, J. Bailey-Wilson, “Genetic epidemiology of breast cancer and associated cancers in high-risk families. II. Linkage analysis,” Journal of the National Cancer Institute 71 (September 1983): 463–467.

  Dr. Lynch’s first suggestion of prophylactic surgery: H. T. Lynch, R. E. Harris, C. H. Organ Jr., H. A. Guirgis, P. M. Lynch, J. F. Lynch, E. J. Nelson, “The surgeon, genetics, and cancer control: The Cancer Family Syndrome,” Annals of Surgery 185 (April 1977): 435–440.

  Dr. Lynch’s criticism of colleagues’ failure to catch hereditary cancer: H. T. Lynch, S. J. Lanspa, B. M. Boman, T. Smyrk, P. Watson, J. F. Lynch, P. M. Lynch, G. Cristofaro, P. Bufo, A. V. Tauro, et al., “Hereditary
nonpolyposis colorectal cancer—Lynch syndromes I and II,” Gastroenterology Clinics of North America 17 (December 1988): 679–712; H. T. Lynch, E. K. Bronson, P. C. Strayhorn, T. C. Smyrk, J. F. Lynch, E. J. Ploetner, “Genetic diagnosis of Lynch syndrome II in an extended colorectal cancer-prone family,” Cancer 66 (November 1990): 2233–2238; H. T. Lynch, T. C. Smyrk, S. J. Lanspa, J. X. Jenkins, J. Cavalieri, J. F. Lynch, “Cancer control problems in the Lynch syndromes,” Diseases of the Colon and Rectum 36 (March 1993): 254–260.

  The story of Dr. Lynch’s testifying at a malpractice trial: H. T. Lynch, J. Paulson, M. Severin, J. Lynch, P. Lynch, “Failure to diagnose hereditary colorectal cancer and its medicolegal implications: A hereditary nonpolyposis colorectal cancer case,” Diseases of the Colon and Rectum 42 ( January 1999): 31–35.

  Dr. Lynch complained that physicians had failed to act on genetic discoveries in H. T. Lynch, T. C. Smyrk, “Hereditary colorectal cancer,” Seminars in Oncology 26 (October 1999): 478–484.

  Papers that report the identification of the Lynch syndrome chromosomes, genes, and mutations: H. T. Lynch, T. C. Smyrk, J. Cavalieri, J. F. Lynch, “Identification of an HNPCC family,” American Journal of Gastroenterology, April 1994, 605–609; H. T. Lynch, J. F. Lynch, “25 years of HNPCC,” Anticancer Research, July—August 1994, 1617–1624 (this is also the paper where the Lynches report that they have started to offer their patients the option of a prophylactic subtotal colectomy); H. T. Lynch, J. F. Lynch, “Clinical implications of advances in the molecular genetics of colorectal cancer,” Tumori, May—June 1995, 19–29; H. T. Lynch, J. F. Lynch, “Genetics of colonic cancer,” Digestion, August 1998, 481–492.

  Lynch papers that describe his tracking of families: H. T. Lynch, P. Watson, M. Kriegler, J. F. Lynch, S. J. Lanspa, J. Marcus, T. Smyrk, R. J. Fitzgibbons Jr., G. Cristofaro, “Differential diagnosis of hereditary nonpolyposis colorectal cancer (Lynch syndrome I and Lynch syndrome II),” Diseases of the Colon and Rectum 31 (May 1988): 372–377; H. T. Lynch, J. Ens, J. F. Lynch, P. Watson, “Tumor variation in three extended Lynch syndrome II kindreds,” American Journal of Gastroenterology 83 (July 1988): 741–747; H. T. Lynch, M. Kriegler, T. A. Christiansen, T. Smyrk, J. F. Lynch, P. Watson, “Laryngeal carcinoma in a Lynch syndrome II kindred,” Cancer 62 (September 1988): 1007–1013; H. T. Lynch, T. Drouhard, H. F. Vasen, J. Cavalieri, J. Lynch, S. Nord, T. Smyrk, S. Lanspa, P. Murphy, K. L. Whelan, J. Peters, A. de la Chapelle, “Genetic counseling in a Navajo hereditary nonpolyposis colorectal cancer kindred,” Cancer 77 (January 1996): 30–35; H. T. Lynch, T. Smyrk, “Hereditary nonpolyposis colorectal cancer (Lynch syndrome). An updated review,” Cancer 78 (September 1996): 1149–1167.

  Paper reporting that half the patients would consider surgery: H. T. Lynch, S. Lemon, T. Smyrk, B. Franklin, B. Karr, J. Lynch, S. Slominski-Caster, P. Murphy, C. Connolly, “Genetic counseling in hereditary nonpolyposis colorectal cancer: An extended family with MSH2 mutation,” American Journal of Gastroenterology 91 (December 1996): 2489–2493.

  Paper reporting that the risk will most often be adjusted down following family testing: P. Watson, S. A. Narod, R. Fodde, A. Wagner, J. F. Lynch, S. T. Tinley, C. L. Snyder, S. A. Coronel, B. Riley, Y. Kinarsky, H. T. Lynch, “Carrier risk status changes resulting from mutation testing in hereditary non-polyposis colorectal cancer and hereditary breast-ovarian cancer,” Journal of Medical Genetics 40 (August 2003): 591–596.

  Dr. Lynch introduces the term “cancer destiny”: H. T. Lynch, T. Smyrk, J. Lynch, “An update of HNPCC (Lynch syndrome),” Cancer Genetics and Cytogenetics 93 (January 1997): 84–99.

  Family information services: H. T. Lynch, S. J. Lemon, B. Karr, B. Franklin, J. F. Lynch, P. Watson, S. Tinley, C. Lerman, C. Carter, “Etiology, natural history, management and molecular genetics of hereditary nonpolyposis colorectal cancer (Lynch syndromes): Genetic counseling implications,” Cancer Epidemiology Biomarkers & Prevention 6 (December 1997): 987–991.

  Alicia Chang, Malcolm Ritter, “11 cousins give up stomachs after tests,” Associated Press, June 18, 2006.

  CHAPTER 7: THE CRUELEST DISEASE

  On disease onset and progression: Sandra Close Kirkwood, Jessica L. Su, Michael Conneally, Tatiana Foroud, “Progression of symptoms in the early and middle stages of Huntington disease,” Archives of Neurology 58 (February 2001): 273; J. S. Paulsen, H. Zhao, J. C. Stout, R. R. Brinkman, M. Guttman, C. A. Ross, P. Como, C. Manning, M. R. Hayden, I. Shoulson, Huntington Study Group, “Clinical markers of early disease in persons near onset of Huntington’s disease,” Neurology 57 (August 2001): 658–662; S. A. Reading, M. A. Yassa, A. Bakker, A. C. Dziorny, L. M. Gourley, V. Yallapragada, A. Rosenblatt, R. L. Margolis, E. H. Aylward, J. Brandt, S. Mori, P. van Zijl, S. S. Bassett, C. A. Ross, “Regional white matter change in presymptomatic Huntington’s disease: A diffusion tensor imaging study,” Psychiatry Research 140 (October 2005): 55–62; Understanding Huntington Disease: A Resource for Families, published by the Huntington Society of Canada, 2002; Jane S. Paulsen, Understanding Behaviour in Huntington Disease: A Practical Guide for Individuals, Families and Professionals Coping with HD, published by the Huntington Society of Canada, 2002; Adam Rosenblatt, Neal Ranen, Martha Nance, Jane Paulsen, A Physician’s Guide to the Management of Huntington Disease, Second Edition, published by the Huntington Society of Canada, 2004.

  “True dominance” in Huntington’s and lack of it in hereditary cancers: Yolanda Narain, Andreas Wyttenbach, Julia Rankin, Robert A. Furlong, David C. Rubinsztein, “A molecular investigation of true dominance in Huntington’s disease,” Journal of Medical Genetics 36 (October 1999): 739–746; N. S. Wexler, A. B. Young, R. E. Tanzi, H. Travers, S. Starosta-Rubinstein, J. B. Penney, S. R. Snodgrass, I. Shoulson, F. Gomez, M. A. Ramos Arroyo, et al., “Homozygotes for Huntington’s disease,” Nature 326 (March 12, 1987): 194–197; T. Ludwig, D. L. Chapman, V. E. Papaioannou, A. Efstratiadis, “Targeted mutations of breast cancer susceptibility gene homologs in mice: Lethal phenotypes of Brca1, Brca2, Brca1/Brca2, Brca1/p53, and Brca2/p53 nullizygous embryos,” Genes & Development 11 (May 15, 1997): 1226–1241.

  The search for the gene is described in Alice Wexler, Mapping Fate: A Memoir of Family, Risk, and Genetic Research (Berkeley: University of California Press, 1996).

  Jean Baréma, The Test: Living in the Shadow of Huntington’s Disease (New York: Franklin Square Press, 2005).

  Early studies of attitudes toward predictive testing were described in: B. Teltscher, S. Polgar, “Objective knowledge about Huntington’s disease and attitudes towards predictive tests of persons at risk,” Journal of Medical Genetics 18 (February 1981): 31–39; A. Tyler, P. S. Harper, “Attitudes of subjects at risk and their relatives towards genetic counseling in Huntington’s chorea,” Journal of Medical Genetics 20 (June 1983): 179–188; S. Kessler, T. Field, L. Worth, H. Mosbarger, “Attitudes of persons at risk for Huntington disease toward predictive testing,” American Journal of Medical Genetics 26 (February 1987): 259–270; G. J. Meissen, R. L. Berchek, “Intended use of predictive testing by those at risk for Huntington disease,” American Journal of Medical Genetics 26 (February 1987): 283–293.

  Statistics on the use of predictive testing prior to 1992 and Nancy Wexler’s comments on 60 Minutes are cited in Alice Wexler, Mapping Fate.

  Transcript of the 2004 CBS News story quoting Nancy Wexler: http://www.cbsnews.com/stories/2004/11/18/eveningnews/main656527.shtml?CMP=ILC-SearchStories (accessed September 13, 2007).

  Study of why people choose not to get tested: K. A. Quaid, M. Morris, “Reluctance to undergo predictive testing: The case of Huntington disease,” American Journal of Medical Genetics 45 (January 1993): 41–45; study showing that those who learned of their status as adults were more likely to get tested: I. M. Van der Steenstraten, A. Tibben, R. A. C. Roos, et al., “Predictive testing for Huntington’s disease: Nonparticipants compared with participants in the Dutch program,” American Journal of Human Genetics 55 (December 1994): 618–625.

  Current rates of presy
mptomatic testing for Huntington’s: Peter S. Harpera, Caron Lima, David Craufurdb, on behalf of the UK Huntington’s Disease Prediction Consortium, “Ten years of presymptomatic testing for Huntington’s disease: The experience of the UK Huntington’s Disease Prediction Consortium,” Journal of Medical Genetics 37 (August 2000): 567–571; M. P. Solis-Perez, J. A. Burguera, F. Palau, L. Livianos, M. Vila, L. Rojo [Results of a program of presymptomatic diagnosis of Huntington’s disease: Evaluation of a six-year period], article in Spanish, Neurologia 16 (October 2001): 348–352; P. Mandich, G. Jacopini, E. Di Maria, G. Sabbadini, G. Abbruzzese, F. Chimirri, E. Bellone, A. Noveletto, F. Ajmar, M. Frontali, “Predictive testing for Huntington’s disease: Ten years’ experience in two Italian centres,” Italian Journal of Neurological Sciences 19 (June 1998): 68–74; S. Creighton, E. W. Almqvist, D. MacGregor, B. Fernandez, H. Hogg, J. Beis, J. P. Welch, C. Riddell, R. Lokkesmoe, M. Khalifa, J. MacKenzie, A. Sajoo, S. Farrell, F. Robert, A. Shugar, A. Summers, W. Meschino, D. Allingham-Hawkins, T. Chiu, A. Hunter, J. Allanson, H. Hare, J. Schween, L. Collins, S. Sanders, C. Greenberg, S. Cardwell, E. Lemire, P. MacLeod, M. R. Hayden, “Predictive, prenatal and diagnostic genetic testing for Huntington’s disease: The experience in Canada from 1987 to 2000,” Clinical Genetics 63 (June 2003): 462–475.

  CHAPTER 8: THE SCIENCE OF MATCHMAKING

  On genetic imperatives in Jewish law: Rosner, “Judaism, genetic screening and genetic therapy.”

  On leprosy and genetics: A. Alcais, M. Mira, J. L. Casanova, E. Schurr, L. Abel, “Genetic dissection of immunity in leprosy,” Current Opinion in Immunology 17 (February 2005): 44–48.