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17 - Genetic approaches to treating and preventing symptoms in patients with cancer

from Section 2 - Cancer Symptom Mechanisms and Models: Clinical and Basic Science

Published online by Cambridge University Press:  05 August 2011

Qiuling Shi
Affiliation:
The University of Texas M. D. Anderson Cancer Center
Charles S. Cleeland
Affiliation:
The University of Texas M. D. Anderson Cancer Center
Charles S. Cleeland
Affiliation:
University of Texas, M. D. Anderson Cancer Center
Michael J. Fisch
Affiliation:
University of Texas, M. D. Anderson Cancer Center
Adrian J. Dunn
Affiliation:
University of Hawaii, Manoa
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Summary

Disease-related and treatment-related symptoms vary among patients with cancer, even when disease severity and treatment modality are comparable. Numerous studies document that age, gender, race/ethnicity, mood states, and other environmental factors can influence the individual's symptom experience. However, the large interindividual variation not explained by such factors suggests that genetic characteristics may contribute to the variability. Genetic variations and the differences in proteins they encode affect individuals' predispositions to symptoms and to other common diseases. As a complex process, development of cancer-related symptoms is influenced by multiple genetic variations, each of which makes a small contribution to the patient's overall symptom susceptibility.

Identifying the associations between cancer-related symptoms and common genetic variations provides several potential benefits. First, investigating the relationship between patients' genetic variations and their predispositions to certain symptoms may reveal the biological mechanisms or pathways governing symptom development. Second, determining the genotypes that are highly correlated to specific symptoms may help clinicians identify patients who have a high risk for symptom burden and who would benefit from preventive therapy. Third, using genotypes to evaluate an individual patient's sensitivity to specific treatments could enable clinicians to manage multiple symptoms by targeting underlying biological mechanisms instead of treating individual symptoms empirically (eg, stimulants for fatigue, opioids for pain). Controlling or even preventing symptoms in such a personalized way would potentially benefit thousands of cancer patients and survivors.

Type
Chapter
Information
Cancer Symptom Science
Measurement, Mechanisms, and Management
, pp. 192 - 205
Publisher: Cambridge University Press
Print publication year: 2010

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References

Einfeld, S, Hall, W. Behavior phenotype of the fragile X syndrome. Am J Med Genet 43(1–2):56–60, 1992.CrossRefGoogle ScholarPubMed
Miller, AH. Cytokines and sickness behavior: implications for cancer care and control. Brain Behav Immun 17(Suppl 1):S132–S134, 2003.CrossRefGoogle ScholarPubMed
Lee, BN, Dantzer, R, Langley, KE, et al. A cytokine-based neuroimmunologic mechanism of cancer-related symptoms. Neuroimmunomodulation 11(5):279–292, 2004.CrossRefGoogle ScholarPubMed
Cleeland, CS. Symptom burden: multiple symptoms and their impact as patient-reported outcomes. J Natl Cancer Inst Monogr 37:16–21, 2007.CrossRefGoogle Scholar
Clatworthy, J, Buick, D, Hankins, M, Weinman, J, Horne, R. The use and reporting of cluster analysis in health psychology: a review. Br J Health Psychol 10(Pt 3):329–358, 2005.CrossRefGoogle ScholarPubMed
Nagin, DS, Tremblay, RE. Analyzing developmental trajectories of distinct but related behaviors: a group-based method. Psychol Methods 6(1):18–34, 2001.CrossRefGoogle ScholarPubMed
Zubieta, JK, Heitzeg, MM, Smith, YR, et al. COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science 299(5610):1240–1243, 2003.CrossRefGoogle ScholarPubMed
Diatchenko, L, Slade, GD, Nackley, AG, et al. Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet 14(1):135–143, 2005.CrossRefGoogle ScholarPubMed
Rakvåg, TT, Ross, JR, Sato, H, Skorpen, F, Kaasa, S, Klepstad, P. Genetic variation in the catechol-O-methyltransferase (COMT) gene and morphine requirements in cancer patients with pain. Mol Pain 4:64, 2008.CrossRefGoogle ScholarPubMed
Max, MB, Wu, T, Atlas, SJ, et al. A clinical genetic method to identify mechanisms by which pain causes depression and anxiety. Mol Pain 2:14, 2006.CrossRefGoogle ScholarPubMed
Hunt, R, Sauna, ZE, Ambudkar, SV, Gottesman, MM, Kimchi-Sarfaty, C. Silent (synonymous) SNPs: should we care about them?Methods Mol Biol 578:23–39, 2009.CrossRefGoogle Scholar
Nackley, AG, Shabalina, SA, Tchivileva, IE, et al. Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science 314(5807):1930–1933, 2006.CrossRefGoogle ScholarPubMed
Kawaguchi, Y, Tochimoto, A, Hara, M, et al. Contribution of single nucleotide polymorphisms of the IL1A gene to the cleavage of precursor IL-1alpha and its transcription activity. Immunogenetics 59(6):441–448, 2007.CrossRefGoogle ScholarPubMed
Gabriel, SB, Schaffner, SF, Nguyen, H, et al. The structure of haplotype blocks in the human genome. Science 296(5576):2225–2229, 2002.CrossRefGoogle ScholarPubMed
,National Institute of Environmental Health Sciences. Environmental Genome Project: NIEHS SNPs. Available from: URL: http://egp.gs.washington.edu/. Accessed Mar 21, 2010.
Johnson, GC, Esposito, L, Barratt, BJ, et al. Haplotype tagging for the identification of common disease genes. Nat Genet 29(2):233–237, 2001.CrossRefGoogle ScholarPubMed
Stram, , Haiman, CA, Hirschhorn, JN, et al. Choosing haplotype-tagging SNPS based on unphased genotype data using a preliminary sample of unrelated subjects with an example from the Multiethnic Cohort Study. Hum Hered 55(1):27–36, 2003.CrossRefGoogle ScholarPubMed
Wall, JD, Pritchard, JK. Haplotype blocks and linkage disequilibrium in the human genome. Nat Rev Genet 4(8):587–597, 2003.CrossRefGoogle ScholarPubMed
Chapman, JM, Cooper, JD, Todd, JA, Clayton, DG. Detecting disease associations due to linkage disequilibrium using haplotype tags: a class of tests and the determinants of statistical power. Hum Hered 56(1–3):18–31, 2003.CrossRefGoogle ScholarPubMed
Carlson, CS, Eberle, MA, Rieder, MJ, Yi, Q, Kruglyak, L, Nickerson, DA. Selecting a maximally informative set of single-nucleotide polymorphisms for association analyses using linkage disequilibrium. Am J Hum Genet 74(1):106–120, 2004.CrossRefGoogle ScholarPubMed
Yang, Y, Wang, Y, Li, S, et al. Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia. J Med Genet 41(3):171–174, 2004.CrossRefGoogle ScholarPubMed
Max, MB. Assessing pain candidate gene studies. Pain 109(1–2):1–3, 2004.CrossRefGoogle ScholarPubMed
Armero, P, Muriel, C, Santos, J, Sànchez-Montero, FJ, Rodríguez, RE, González-Sarmiento, R. COMT (Val158Met) polymorphism is not associated to neuropathic pain in a Spanish population. Eur J Pain 9(3):229–232, 2005.CrossRefGoogle ScholarPubMed
Kim, H, Lee, H, Rowan, J, Brahim, J, Dionne, RA. Genetic polymorphisms in monoamine neurotransmitter systems show only weak association with acute post-surgical pain in humans. Mol Pain 2:24, 2006.CrossRefGoogle ScholarPubMed
Hoggart, CJ, Clark, TG, Iorio, M, Whittaker, JC, Balding, DJ. Genome-wide significance for dense SNP and resequencing data. Genet Epidemiol 32(2):179–185, 2008.CrossRefGoogle ScholarPubMed
McCarthy, MI, Abecasis, GR, Cardon, LR, et al. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet 9(5):356–369, 2008.CrossRefGoogle ScholarPubMed
Hindorff, , Sethupathy, P, Junkins, HA, et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci U S A 106(23):9362–9367, 2009.CrossRefGoogle ScholarPubMed
Xu, Z, Taylor, JA. SNPinfo: integrating GWAS and candidate gene information into functional SNP selection for genetic association studies. Nucleic Acids Res 37(Web Server issue):W600–W605, 2009.CrossRefGoogle ScholarPubMed
Rakvåg, TT, Klepstad, P, Báár, C, et al. The Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene may influence morphine requirements in cancer pain patients. Pain 116(1–2):73–78, 2005.CrossRefGoogle ScholarPubMed
Ross, JR, Riley, J, Taegetmeyer, AB, et al. Genetic variation and response to morphine in cancer patients: catechol-O-methyltransferase and multidrug resistance-1 gene polymorphisms are associated with central side effects. Cancer 112(6):1390–1403, 2008.CrossRefGoogle ScholarPubMed
Klepstad, P, Rakvåg, TT, Kaasa, S, et al. The 118 A > G polymorphism in the human mu-opioid receptor gene may increase morphine requirements in patients with pain caused by malignant disease. Acta Anaesthesiol Scand 48(10):1232–1239, 2004.CrossRefGoogle Scholar
Reyes-Gibby, CC, El Osta, B, Spitz, MR, et al. The influence of tumor necrosis factor-alpha -308 G/A and IL-6–174 G/C on pain and analgesia response in lung cancer patients receiving supportive care. Cancer Epidemiol Biomarkers Prev 17(11):3262–3267, 2008.CrossRefGoogle ScholarPubMed
Reyes-Gibby, CC, Spitz, M, Wu, X, et al. Cytokine genes and pain severity in lung cancer: exploring the influence of TNF-alpha-308 G/A IL6–174G/C and IL8–251T/A. Cancer Epidemiol Biomarkers Prev 16(12):2745–2751, 2007.CrossRefGoogle ScholarPubMed
Campa, D, Gioia, A, Tomei, A, Poli, P, Barale, R. Association of ABCB1/MDR1 and OPRM1 gene polymorphisms with morphine pain relief. Clin Pharmacol Ther 83(4):559–566, 2008.CrossRefGoogle ScholarPubMed
Klepstad, P, Dale, O, Skorpen, F, Borchgrevink, PC, Kaasa, S. Genetic variability and clinical efficacy of morphine. Acta Anaesthesiol Scand 49(7):902–908, 2005.CrossRefGoogle ScholarPubMed
Dantzer, R, Kelley, KW. Twenty years of research on cytokine-induced sickness behavior. Brain Behav Immun 21(2):153–160, 2007.CrossRefGoogle ScholarPubMed
Bower, JE, Ganz, PA, Tao, ML, et al. Inflammatory biomarkers and fatigue during radiation therapy for breast and prostate cancer. Clin Cancer Res 15(17):5534–5540, 2009.CrossRefGoogle ScholarPubMed
Wang, XS, Shi, Q, Williams, , et al. Serum interleukin-6 predicts the development of multiple symptoms at nadir of allogeneic hematopoietic stem cell transplantation. Cancer 113(8):2102–2109, 2008.CrossRefGoogle ScholarPubMed
Reeve, AJ, Patel, S, Fox, A, Walker, K, Urban, L. Intrathecally administered endotoxin or cytokines produce allodynia, hyperalgesia and changes in spinal cord neuronal responses to nociceptive stimuli in the rat. Eur J Pain 4(3):247–257, 2000.CrossRefGoogle ScholarPubMed
Song, C, Horrobin, DF, Leonard, BE. The comparison of changes in behavior, neurochemistry, endocrine, and immune functions after different routes, doses and durations of administrations of IL-1beta in rats. Pharmacopsychiatry 39(3):88–99, 2006.CrossRefGoogle ScholarPubMed
Dominici, R, Cattaneo, M, Malferrari, G, et al. Cloning and functional analysis of the allelic polymorphism in the transcription regulatory region of interleukin-1 alpha. Immunogenetics 54(2):82–86, 2002.CrossRefGoogle ScholarPubMed
Pociot, F, Mølvig, J, Wogensen, L, Worsaae, H, Nerup, J. A TaqI polymorphism in the human interleukin-1 beta (IL-1 beta) gene correlates with IL-1 beta secretion in vitro. Eur J Clin Invest 22(6):396–402, 1992.CrossRefGoogle ScholarPubMed
di Giovine, FS, Takhsh, E, Blakemore, AI, Duff, GW. Single base polymorphism at -511 in the human interleukin-1 beta gene (IL1 beta). Hum Mol Genet 1(6):450, 1992.CrossRefGoogle Scholar
Tarlow, JK, Blakemore, AI, Lennard, A, et al. Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat. Hum Genet 91(4):403–404, 1993.CrossRefGoogle ScholarPubMed
Sakamoto, K, Oka, M, Yoshino, S, et al. Relation between cytokine promoter gene polymorphism and toxicity of 5-fluorouracil plus cisplatin chemotherapy. Oncol Rep 16(2):381–387, 2006.Google ScholarPubMed
Collado-Hidalgo, A, Bower, JE, Ganz, PA, Irwin, MR, Cole, SW. Cytokine gene polymorphisms and fatigue in breast cancer survivors: early findings. Brain Behav Immun 22(8):1197–1200, 2008.CrossRefGoogle ScholarPubMed
Solovieva, S, Leino-Arjas, P, Saarela, J, Luoma, K, Raininko, R, Riihimäki, H. Possible association of interleukin 1 gene locus polymorphisms with low back pain. Pain 109(1–2):8–19, 2004.CrossRefGoogle ScholarPubMed
Bessler, H, Shavit, Y, Mayburd, E, Smirnov, G, Beilin, B. Postoperative pain, morphine consumption, and genetic polymorphism of IL-1beta and IL-1 receptor antagonist. Neurosci Lett 404(1–2):154–158, 2006.CrossRefGoogle ScholarPubMed
Bianchi, M, Maggi, R, Pimpinelli, F, et al. Presence of a reduced opioid response in interleukin-6 knock out mice. Eur J Neurosci 11(5):1501–1507, 1999.CrossRefGoogle ScholarPubMed
Boufidou, F, Lambrinoudaki, I, Argeitis, J, et al. CSF and plasma cytokines at delivery and postpartum mood disturbances. J Affect Disord 115(1–2):287–292, 2009.CrossRefGoogle ScholarPubMed
Lutgendorf, SK, Weinrib, AZ, Penedo, F, et al. Interleukin-6, cortisol, and depressive symptoms in ovarian cancer patients. J Clin Oncol 26(29):4820–4827, 2008.CrossRefGoogle ScholarPubMed
Jacobson, CM, Rosenfeld, B, Pessin, H, Breitbart, W. Depression and IL-6 blood plasma concentrations in advanced cancer patients. Psychosomatics 49(1):64–66, 2008.CrossRefGoogle ScholarPubMed
Bremmer, MA, Beekman, AT, Deeg, DJ, et al. Inflammatory markers in late-life depression: results from a population-based study. J Affect Disord 106(3):249–255, 2008.CrossRefGoogle ScholarPubMed
Hogan, D, Morrow, JD, Smith, EM, Opp, MR. Interleukin-6 alters sleep of rats. J Neuroimmunol 137(1–2):59–66, 2003.CrossRefGoogle ScholarPubMed
Dugan, LL, Ali, SS, Shekhtman, G, et al. IL-6 mediated degeneration of forebrain GABAergic interneurons and cognitive impairment in aged mice through activation of neuronal NADPH oxidase. PLoS One 4(5):e5518, 2009.CrossRefGoogle ScholarPubMed
Fishman, D, Faulds, G, Jeffery, R, et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 102(7):1369–1376, 1998.CrossRefGoogle ScholarPubMed
Bull, SJ, Huezo-Diaz, P, Binder, EB, et al. Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment. Mol Psychiatry 14(12):1095–1104, 2009.CrossRefGoogle ScholarPubMed
Oen, K, Malleson, PN, Cabral, DA, et al. Cytokine genotypes correlate with pain and radiologically defined joint damage in patients with juvenile rheumatoid arthritis. Rheumatology (Oxford) 44(9):1115–1121, 2005.CrossRefGoogle ScholarPubMed
Karppinen, J, Daavittila, I, Noponen, N, et al. Is the interleukin-6 haplotype a prognostic factor for sciatica?Eur J Pain 12(8):1018–1025, 2008.CrossRefGoogle ScholarPubMed
Sommer, C, Petrausch, S, Lindenlaub, T, Toyka, KV. Neutralizing antibodies to interleukin 1-receptor reduce pain associated behavior in mice with experimental neuropathy. Neurosci Lett 270(1):25–28, 1999.CrossRefGoogle ScholarPubMed
Utreras, E, Futatsugi, A, Rudrabhatla, P, et al. Tumor necrosis factor-alpha regulates cyclin-dependent kinase 5 activity during pain signaling through transcriptional activation of p35. J Biol Chem 284(4):2275–2284, 2009.CrossRefGoogle ScholarPubMed
Wilson, AG, Symons, JA, McDowell, TL, McDevitt, HO, Duff, GW. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci U S A 94(7):3195–3199, 1997.CrossRefGoogle ScholarPubMed
Cerri, AP, Arosio, B, Viazzoli, C, Confalonieri, R, Vergani, C, Annoni, G. The -308 (G/A) single nucleotide polymorphism in the TNF-alpha gene and the risk of major depression in the elderly. Int J Geriatr Psychiatry 25(3):219–223, 2010.CrossRefGoogle ScholarPubMed
Jun, TY, Pae, CU, Chae, JH, et al. Tumor necrosis factor-beta gene polymorphism may not be associated with major depressive disorder in the Korean population. Psychiatry Clin Neurosci 57(1):31–35, 2003.CrossRefGoogle Scholar
Matsushima, K, Baldwin, ET, Mukaida, N. Interleukin-8 and MCAF: novel leukocyte recruitment and activating cytokines. Chem Immunol 51:236–265, 1992.Google ScholarPubMed
Ahn, SH, Cho, YW, Ahn, MW, Jang, SH, Sohn, YK, Kim, HS. mRNA expression of cytokines and chemokines in herniated lumbar intervertebral discs. Spine (Phila Pa 1976) 27(9):911–917, 2002.Google Scholar
Hull, J, Thomson, A, Kwiatkowski, D. Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families. Thorax 55(12):1023–1027, 2000.CrossRefGoogle ScholarPubMed
Babovic, D, O'Tuathaigh, CM, O'Connor, AM, et al. Phenotypic characterization of cognition and social behavior in mice with heterozygous versus homozygous deletion of catechol-O-methyltransferase. Neuroscience 155(4):1021–1029, 2008.CrossRefGoogle ScholarPubMed
Sambataro, F, Reed, JD, Murty, VP, et al. Catechol-O-methyltransferase valine(158)methionine polymorphism modulates brain networks underlying working memory across adulthood. Biol Psychiatry 66(6):540–548, 2009.CrossRefGoogle ScholarPubMed
Mata, I, Arranz, MJ, Staddon, S, Lopez-Ilundain, JM, Tabares-Seisdedos, R, Murray, RM. The high-activity Val allele of the catechol-O-methyltransferase gene predicts greater cognitive deterioration in patients with psychosis. Psychiatr Genet 16(5):213–216, 2006.CrossRefGoogle ScholarPubMed
Han, DH, Kee, BS, Min, KJ, et al. Effects of catechol-O-methyltransferase Val158Met polymorphism on the cognitive stability and aggression in the first-onset schizophrenic patients. Neuroreport 17(1):95–99, 2006.CrossRefGoogle ScholarPubMed
Weickert, TW, Goldberg, TE, Mishara, A, et al. Catechol-O-methyltransferase val108/158met genotype predicts working memory response to antipsychotic medications. Biol Psychiatry 56(9):677–682, 2004.CrossRefGoogle ScholarPubMed
Barnett, JH, Scoriels, L, Munafò, MR. Meta-analysis of the cognitive effects of the catechol-O-methyltransferase gene Val158/108Met polymorphism. Biol Psychiatry 64(2):137–144, 2008.CrossRefGoogle ScholarPubMed
Benedetti, F, Barbini, B, Bernasconi, A, et al. Acute antidepressant response to sleep deprivation combined with light therapy is influenced by the catechol-O-methyltransferase Val(108/158)Met polymorphism. J Affect Disord 121(1–2):68–72, 2010.CrossRefGoogle Scholar
Benedetti, F, Colombo, C, Pirovano, A, Marino, E, Smeraldi, E. The catechol-O-methyltransferase Val(108/158)Met polymorphism affects antidepressant response to paroxetine in a naturalistic setting. Psychopharmacology (Berl) 203(1):155–160, 2009.CrossRefGoogle Scholar
Anttila, S, Huuhka, K, Huuhka, M, et al. Catechol-O-methyltransferase (COMT) polymorphisms predict treatment response in electroconvulsive therapy. Pharmacogenomics J 8(2):113–116, 2008.CrossRefGoogle ScholarPubMed
Pert, CB, Snyder, SH. Opiate receptor: demonstration in nervous tissue. Science 179(77):1011–1014, 1973.CrossRefGoogle ScholarPubMed
Stein, C. Peripheral mechanisms of opioid analgesia. Anesth Analg 76(1):182–191, 1993.CrossRefGoogle ScholarPubMed
Bidlack, JM, Khimich, M, Parkhill, AL, Sumagin, S, Sun, B, Tipton, CM. Opioid receptors and signaling on cells from the immune system. J Neuroimmune Pharmacol 1(3):260–269, 2006.CrossRefGoogle ScholarPubMed
McQuay, H. Opioids in pain management. Lancet 353(9171):2229–2232, 1999.CrossRefGoogle ScholarPubMed
Bond, C, LaForge, KS, Tian, M, et al. Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci U S A 95(16):9608–9613, 1998.CrossRefGoogle ScholarPubMed
Oertel, BG, Kettner, M, Scholich, K, et al. A common human μ-opioid receptor genetic variant diminishes the receptor signaling efficacy in brain regions processing the sensory information of pain. J Biol Chem 284(10):6530–6535, 2009.CrossRefGoogle Scholar
Sia, AT, Lim, Y, Lim, EC, et al. A118G single nucleotide polymorphism of human mu-opioid receptor gene influences pain perception and patient-controlled intravenous morphine consumption after intrathecal morphine for postcesarean analgesia. Anesthesiology 109(3):520–526, 2008.CrossRefGoogle ScholarPubMed
Chou, WY, Wang, CH, Liu, PH, Liu, CC, Tseng, CC, Jawan, B. Human opioid receptor A118G polymorphism affects intravenous patient-controlled analgesia morphine consumption after total abdominal hysterectomy. Anesthesiology 105(2):334–337, 2006.CrossRefGoogle ScholarPubMed
Landau, R, Kern, C, Columb, MO, Smiley, RM, Blouin, JL. Genetic variability of the mu-opioid receptor influences intrathecal fentanyl analgesia requirements in laboring women. Pain 139(1):5–14, 2008.CrossRefGoogle ScholarPubMed
Zhang, H, Shi, YG, Woods, JH, Watson, SJ, Ko, MC. Central kappa-opioid receptor-mediated antidepressant-like effects of nor-Binaltorphimine: behavioral and BDNF mRNA expression studies. Eur J Pharmacol 570(1–3):89–96, 2007.CrossRefGoogle ScholarPubMed
Blakely, RD, Felice, LJ, Hartzell, HC. Molecular physiology of norepinephrine and serotonin transporters. J Exp Biol 196:263–281, 1994.Google ScholarPubMed
Lesch, KP, Bengel, D, Heils, A, et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274(5292):1527–1531, 1996.CrossRefGoogle ScholarPubMed
Heils, A, Teufel, A, Petri, S, et al. Allelic variation of human serotonin transporter gene expression. J Neurochem 66(6):2621–2624, 1996.CrossRefGoogle ScholarPubMed
Caspi, A, Sugden, K, Moffitt, TE, et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301(5631):386–389, 2003.CrossRefGoogle ScholarPubMed
Kosek, E, Jensen, KB, Lonsdorf, TB, Schalling, M, Ingvar, M. Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid Remifentanil in humans. Mol Pain 5:37, 2009.CrossRefGoogle ScholarPubMed
Schillani, G, Capozzo, MA, Aguglia, E, et al. 5-HTTLPR polymorphism of serotonin transporter and effects of sertraline in terminally ill cancer patients: report of eleven cases. Tumori 94(4):563–567, 2008.CrossRefGoogle ScholarPubMed
Herken, H, Erdal, E, Mutlu, N, et al. Possible association of temporomandibular joint pain and dysfunction with a polymorphism in the serotonin transporter gene. Am J Orthod Dentofacial Orthop 120(3):308–313, 2001.CrossRefGoogle ScholarPubMed
King, M, Su, W, Chang, A, Zuckerman, A, Pasternak, GW. Transport of opioids from the brain to the periphery by P-glycoprotein: peripheral actions of central drugs. Nat Neurosci 4(3):268–274, 2001.CrossRefGoogle ScholarPubMed
Schinkel, AH, Wagenaar, E, Deemter, L, Mol, CA, Borst, P. Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. J Clin Invest 96(4):1698–1705, 1995.CrossRefGoogle ScholarPubMed
Thompson, SJ, Koszdin, K, Bernards, CM. Opiate-induced analgesia is increased and prolonged in mice lacking P-glycoprotein. Anesthesiology 92(5):1392–1399, 2000.CrossRefGoogle ScholarPubMed
Higgins, CF. ABC transporters: physiology, structure and mechanism: an overview. Res Microbiol 152(3–4):205–210, 2001.CrossRefGoogle ScholarPubMed
Hoffmeyer, S, Burk, O, Richter, O, et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A 97(7):3473–3478, 2000.CrossRefGoogle ScholarPubMed
Lötsch, J, Hentig, N, Freynhagen, R, et al. Cross-sectional analysis of the influence of currently known pharmacogenetic modulators on opioid therapy in outpatient pain centers. Pharmacogenet Genomics 19(6):429–436, 2009.CrossRefGoogle ScholarPubMed
Coller, JK, Barratt, DT, Dahlen, K, Loennechen, MH, Somogyi, AA. ABCB1 genetic variability and methadone dosage requirements in opioid-dependent individuals. Clin Pharmacol Ther 80(6):682–690, 2006.CrossRefGoogle ScholarPubMed
Park, HJ, Shinn, HK, Ryu, SH, Lee, HS, Park, CS, Kang, JH. Genetic polymorphisms in the ABCB1 gene and the effects of fentanyl in Koreans. Clin Pharmacol Ther 81(4):539–546, 2007.CrossRefGoogle ScholarPubMed
Kim, HS, Kim, MK, Chung, HH, et al. Genetic polymorphisms affecting clinical outcomes in epithelial ovarian cancer patients treated with taxanes and platinum compounds: a Korean population-based study. Gynecol Oncol 113(2):264–269, 2009.CrossRefGoogle ScholarPubMed
Qian, W, Homma, M, Itagaki, F, et al. MDR1 gene polymorphism in Japanese patients with schizophrenia and mood disorders including depression. Biol Pharm Bull 29(12):2446–2450, 2006.CrossRefGoogle ScholarPubMed
Guengerich, FP. Cytochrome p450 and chemical toxicology. Chem Res Toxicol 21(1):70–83, 2008.CrossRefGoogle ScholarPubMed
Stamer, UM, Musshoff, F, Kobilay, M, Madea, B, Hoeft, A, Stuber, F. Concentrations of tramadol and O-desmethyltramadol enantiomers in different CYP2D6 genotypes. Clin Pharmacol Ther 82(1):41–47, 2007.CrossRefGoogle ScholarPubMed
Zanger, UM, Klein, K, Saussele, T, Blievernicht, J, Hofmann, MH, Schwab, M. Polymorphic CYP2B6: molecular mechanisms and emerging clinical significance. Pharmacogenomics 8(7):743–759, 2007.CrossRefGoogle ScholarPubMed
Leon, J, Susce, MT, Murray-Carmichael, E. The AmpliChip CYP450 genotyping test: integrating a new clinical tool. Mol Diagn Ther 10(3):135–151, 2006.CrossRefGoogle ScholarPubMed
Desmeules, J, Gascon, MP, Dayer, P, Magistris, M. Impact of environmental and genetic factors on codeine analgesia. Eur J Clin Pharmacol 41(1):23–26, 1991.CrossRefGoogle ScholarPubMed
Wang, G, Zhang, H, He, F, Fang, X. Effect of the CYP2D6*10 C188T polymorphism on postoperative tramadol analgesia in a Chinese population. Eur J Clin Pharmacol 62(11):927–931, 2006.CrossRefGoogle ScholarPubMed
Crettol, S, Déglon, JJ, Besson, J, et al. ABCB1 and cytochrome P450 genotypes and phenotypes: influence on methadone plasma levels and response to treatment. Clin Pharmacol Ther 80(6):668–681, 2006.CrossRefGoogle ScholarPubMed
Pilotto, A, Seripa, D, Franceschi, M, et al. Genetic susceptibility to nonsteroidal anti-inflammatory drug-related gastroduodenal bleeding: role of cytochrome P450 2C9 polymorphisms. Gastroenterology 133(2):465–471, 2007.CrossRefGoogle ScholarPubMed
Armstrong, SC, Cozza, KL. Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, part I. Psychosomatics 44(2):167–171, 2003.CrossRefGoogle ScholarPubMed
Holthe, M, Rakvåg, TN, Klepstad, P, et al. Sequence variations in the UDP-glucuronosyltransferase 2B7 (UGT2B7) gene: identification of 10 novel single nucleotide polymorphisms (SNPs) and analysis of their relevance to morphine glucuronidation in cancer patients. Pharmacogenomics J 3(1):17–26, 2003.CrossRefGoogle ScholarPubMed
Duguay, Y, Báár, C, Skorpen, F, Guillemette, C. A novel functional polymorphism in the uridine diphosphate-glucuronosyltransferase 2B7 promoter with significant impact on promoter activity. Clin Pharmacol Ther 75(3):223–233, 2004.CrossRefGoogle ScholarPubMed
Darbari, DS, Schaik, RH, Capparelli, EV, Rana, S, McCarter, R, Anker, J. UGT2B7 promoter variant -840G>A contributes to the variability in hepatic clearance of morphine in patients with sickle cell disease. Am J Hematol 83(3):200–202, 2008.CrossRefGoogle ScholarPubMed
Mogil, JS. Are we getting anywhere in human pain genetics?Pain 146(3):231–232, 2009.CrossRefGoogle ScholarPubMed

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Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

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Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

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Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

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