Genetic basis of interindividual susceptibility to cancer cachexia: selection of potential candidate gene polymorphisms for association studies

Journal of Genetics

Volumn 93, Issue 3, 2014, Pages 893-916

  JOHNS, N ^a   TAN, B H ^b   MACMILLAN, M ^a   SOLHEIM, T S ^c   ROSS, J A ^a   BARACOS, V E ^d   DAMARAJU, S ^d   FEARON, K C H ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b ROYAL DERBY HOSPITAL   (United Kingdom)

^c NORWEGIAN UNIVERSITY OF SCIENCE AND TECHNOLOGY   (Norway)

^d UNIVERSITY OF ALBERTA   (Canada)

Author keywords

cachexia; cancer; genetics; polymorphism

Indexed keywords

CACHEXIA; COMPLICATION; GENETIC ASSOCIATION STUDIES; GENETIC PREDISPOSITION TO DISEASE; GENETICS; HUMANS; NEOPLASMS; PHYSIOPATHOLOGY; POLYMORPHISM, SINGLE NUCLEOTIDE; QUANTITATIVE TRAIT LOCI;

CACHEXIA; GENETIC ASSOCIATION STUDIES; GENETIC PREDISPOSITION TO DISEASE; HUMANS; NEOPLASMS; POLYMORPHISM, SINGLE NUCLEOTIDE; QUANTITATIVE TRAIT LOCI;

EID: 84925538636     PISSN: 00221333     EISSN: 09737731     Source Type: Journal    
DOI: 10.1007/s12041-014-0405-9     Document Type: Article

References (186)

1. Adamo K. B., Dent R., Langefeld C. D., Cox M., Williams K., Carrick K. M., et al. 2007 Peroxisome proliferator-activated receptor gamma 2 and acyl-CoA synthetase 5 polymorphisms influence diet response. Obesity (Silver Spring)15, 1068–1075.
2. Aggarwal B. B., Eessalu T. E., and Hass P. E. 1985 Characterization of receptors for human tumour necrosis factor and their regulation by gamma-interferon. Nature318, 665–667.
3. Ak K., Isbir S., Tekeli A., Ergen A., Atalan N., Dogan S., et al. 2007 Presence of lipoprotein lipase S447X stop codon affects the magnitude of interleukin 8 release after cardiac surgery with cardiopulmonary bypass. J. Thorac. Cardiovasc. Surg.134, 477–483.
4. Alexiou D., Karayiannakis A. J., Syrigos K. N., Zbar A., Kremmyda A., Bramis I., et al. 2001 Serum levels of E-selectin, ICAM-1 and VCAM-1 in colorectal cancer patients: correlations with clinicopathological features, patient survival and tumour surgery. Eur. J. Cancer37, 2392–2397.
5. Alexiou D., Karayiannakis A. J., Syrigos K. N., Zbar A., Sekara E., Michail P., et al. 2003 Clinical significance of serum levels of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in gastric cancer patients. Am. J. Gastroenterol.98, 478–485.
6. Argiles J. M., Busquets S., and Lopez-Soriano F. J. 2003 Cytokines in the pathogenesis of cancer cachexia. Curr. Opin. Clin. Nutr. Metab. Care6, 401–406.
7. Argiles J. M., Anker S. D., Evans W. J., Morley J. E., Fearon K. C., Strasser F., et al. 2010 Consensus on cachexia definitions. J. Am. Med. Dir. Assoc.11, 229–230.
8. Argiles J. M., Lopez-Soriano F. J., Toledo M., Betancourt A., Serpe R., and Busquets S. 2011 The cachexia score (CASCO): a new tool for staging cachectic cancer patients. J. Cachexia Sarcopenia Muscle2, 87–93.
9. Arimitsu J., Hirano T., Higa S., Kawai M., Naka T., Ogata A., et al. 2006 IL-18 gene polymorphisms affect IL-18 production capability by monocytes. Biochem. Biophys. Res. Commun.342, 1413–1416.
10. Awomoyi A. A., Charurat M., Marchant A., Miller E. N., Blackwell J. M., McAdam K. P., et al. 2005 Polymorphism in IL1B: IL1B-511 association with tuberculosis and decreased lipopolysaccharide-induced IL-1beta in IFN-gamma primed ex-vivo whole blood assay. J. Endotoxin Res.11, 281–286.
11. Bao Y., Bing C., Hunter L., Jenkins J. R., Wabitsch M., and Trayhurn P. 2005 Zinc-alpha2-glycoprotein, a lipid mobilizing factor, is expressed and secreted by human (SGBS) adipocytes. FEBS Lett.579, 41–47.
12. Baracos V. E. 2011 Pitfalls in defining and quantifying cachexia. J. Cachexia Sarcopenia Muscle2, 71–73.
13. Barber M. D., Powell J. J., Lynch S. F., Fearon K. C., and Ross J. A. 2000 A polymorphism of the interleukin-1 beta gene influences survival in pancreatic cancer. Br. J. Cancer83, 1443– 1447.
14. Barreiro L. B., Laval G., Quach H., Patin E., and Quintana-Murci L. 2008 Natural selection has driven population differentiation in modern humans. Nat. Genet.40, 340–345.
15. Berthier M. T., Houde A., Cote M., Paradis A. M., Mauriege P., Bergeron J., et al. 2005 Impact of adiponectin gene polymorphisms on plasma lipoprotein and adiponectin concentrations of viscerally obese men. J. Lipid Res.46, 237–244.
16. Bielinski S. J., Reiner A. P., Nickerson D., Carlson C., Bailey K. R., Thyagarajan B., et al. 2011 Polymorphisms in the ICAM1 gene predict circulating soluble intercellular adhesion molecule-1(sICAM-1). Atherosclerosis216, 390–394.
17. Bing C., Russell S. T., Beckett E. E., Collins P., Taylor S., Barraclough R., et al. 2002 Expression of uncoupling proteins-1, -2 and -3 mRNA is induced by an adenocarcinoma-derived lipid-mobilizing factor. Br. J. Cancer86, 612–618.
18. Bing C., Bao Y., Jenkins J., Sanders P., Manieri M., Cinti S., et al. 2004 Zinc-alpha2-glycoprotein, a lipid mobilizing factor, is expressed in adipocytes and is up-regulated in mice with cancer cachexia. Proc. Natl. Acad. Sci. USA101, 2500–2505.
19. Bo S., Dianliang Z., Hongmei Z., Xinxiang W., Yanbing Z., and Xiaobo L. 2010 Association of interleukin-8 gene polymorphism with cachexia from patients with gastric cancer. J. Interferon Cytokine Res.30, 9–14.
20. Bodine S. C., Latres E., Baumhueter S., Lai V. K., Nunez L., Clarke B. A., et al. 2001a Identification of ubiquitin ligases required for skeletal muscle atrophy. Science294, 1704–1708.
21. Bodine S. C., Stitt T. N., Gonzalez M., Kline W. O., Stover G. L., Bauerlein R., et al. 2001b Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat. Cell Biol.3, 1014–1019.
22. Bonetto A., Aydogdu T., Kunzevitzky N., Guttridge D. C., Khuri S., Koniaris L. G., et al. 2011 STAT3 activation in skeletal muscle links muscle wasting and the acute phase response in cancer cachexia. PLoS One6, e22538.
23. Bozzetti F. and Mariani L. 2009 Defining and classifying cancer cachexia: a proposal by the SCRINIO Working Group. J. Parenter Enteral Nutr.33, 361–367.
24. Brink M., Price S. R., Chrast J., Bailey J. L., Anwar A., Mitch W. E., et al. 2001 Angiotensin II induces skeletal muscle wasting through enhanced protein degradation and down-regulates autocrine insulin-like growth factor I. Endocrinology142, 1489–1496.
25. Brookes A. J. 1999 The essence of SNPs. Gene234, 177–186.
26. Cho Y. M., Youn B. S., Chung S. S., Kim K. W., Lee H. K., Yu K. Y., et al. 2004 Common genetic polymorphisms in the promoter of resistin gene are major determinants of plasma resistin concentrations in humans. Diabetologia47, 559–565.
27. Costa A. M., Silva A. J., Garrido N. D., Louro H., de Oliveira R. J., and Breitenfeld L. 2009 Association between ACE D allele and elite short distance swimming. Eur. J. Appl. Physiol.106, 785–790.
28. Craig A., Fernandez-Reyes D., Mesri M., McDowall A., Altieri D. C., Hogg N., et al. 2000 A functional analysis of a natural variant of intercellular adhesion molecule-1 (ICAM-1Kilifi). Hum. Mol. Genet.9, 525–530.
29. Dai J., Hu Z., Dong J., Xu L., Pan S., Jiang Y., et al. 2012 Host immune gene polymorphisms were associated with the prognosis of non-small-cell lung cancer in Chinese. Int. J. Cancer130, 671–676.
30. Day C. P., Grove J., Daly A. K., Stewart M. W., Avery P. J., and Walker M. 1998 Tumour necrosis factor-alpha gene promoter polymorphism and decreased insulin resistance. Diabetologia41, 430–434.
31. de la Iglesia N., Veiga-da-Cunha M., Van Schaftingen E., Guinovart J. J., and Ferrer J. C. 1999 Glucokinase regulatory protein is essential for the proper subcellular localisation of liver glucokinase. FEBS Lett.456, 332–338.
32. Deans D. A., Tan B. H., Ross J. A., Rose-Zerilli M., Wigmore S. J., Howell W. M., et al. 2009 Cancer cachexia is associated with the IL10 -1082 gene promoter polymorphism in patients with gastroesophageal malignancy. Am. J. Clin. Nutr.89, 1164– 1172.
33. Degawa-Yamauchi M., Bovenkerk J. E., Juliar B. E., Watson W., Kerr K., Jones R., et al. 2003 Serum resistin (FIZZ3) protein is increased in obese humans. J. Clin. Endocrinol. Metab.88, 5452–5455.
34. Dewys W. D., Begg C., Lavin P. T., Band P. R., Bennett J. M., Bertino J. R., et al. 1980 Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am. J. Med.69, 491–497.
35. Dhiman N., Ovsyannikova I. G., Vierkant R. A., Ryan J. E., Pankratz V. S., Jacobson R. M., et al. 2008 Associations between SNPs in toll-like receptors and related intracellular signaling molecules and immune responses to measles vaccine: preliminary results. Vaccine26, 1731–1736.
36. Diez J. J. and Iglesias P. 2003 The role of the novel adipocyte-derived hormone adiponectin in human disease. Eur. J. Endocrinol.148, 293–300.
37. Dunlop L. C., Skinner M. P., Bendall L. J., Favaloro E. J., Castaldi P. A., Gorman J. J., et al. 1992 Characterization of GMP-140 (P-selectin) as a circulating plasma protein. J. Exp. Med.175, 1147–1150.
38. Fan W., Boston B. A., Kesterson R. A., Hruby V. J., and Cone R. D. 1997 Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature385, 165–168.
39. Fantuzzi G. and Faggioni R. 2000 Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc. Biol.68, 437–446.
40. Fearon K., Strasser F., Anker S. D., Bosaeus I., Bruera E., Fainsinger R. L., et al. 2011 Definition and classification of cancer cachexia: an international consensus. Lancet Oncol.12, 489–495.
41. Fehrmann R. S., Jansen R. C., Veldink J. H., Westra H. J., Arends D., Bonder M. J., et al. 2011 Trans-eQTLs reveal that independent genetic variants associated with a complex phenotype converge on intermediate genes, with a major role for the HLA. PLoS Genet.7, e1002197.
42. Fishman D., Faulds G., Jeffery R., Mohamed-Ali V., Yudkin J. S., Humphries S., et al. 1998 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, 1369–1376.
43. Fraysse B., Guillet C., Huchet-Cadiou C., Camerino D. C., Gascan H., and Leoty C. 2000 Ciliary neurotrophic factor prevents unweighting-induced functional changes in rat soleus muscle. J. Appl. Physiol.88, 1623–1630.
44. Fredrix E. W., Soeters P. B., Rouflart M. J., von Meyenfeldt M. F., and Saris W. H. 1991 Resting energy expenditure in patients with newly detected gastric and colorectal cancers. Am. J. Clin. Nutr.53, 1318–1322.
45. Gamazon E. R., Zhang W., Konkashbaev A., Duan S., Kistner E. O., Nicolae D. L., et al. 2010 SCAN: SNP and copy number annotation. Bioinformatics26, 259–262.
46. Garofalo R. S., Orena S. J., Rafidi K., Torchia A. J., Stock J. L., Hildebrandt A. L., et al. 2003 Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKB beta. J. Clin. Invest.112, 197–208.
47. Glass D. J. 2010 PI3 kinase regulation of skeletal muscle hypertrophy and atrophy. Curr. Top. Microbiol. Immunol.346, 267–278.
48. Graziano F., Ruzzo A., Santini D., Humar B., Tonini G., Catalano V., et al. 2005 Prognostic role of interleukin-1beta gene and interleukin-1 receptor antagonist gene polymorphisms in patients with advanced gastric cancer. J. Clin. Oncol.23, 2339–2345.
49. Groenemeijer B. E., Hallman M. D., Reymer P. W., Gagne E., Kuivenhoven J. A., Bruin T., et al. 1997 Genetic variant showing a positive interaction with beta-blocking agents with a beneficial influence on lipoprotein lipase activity, HDL cholesterol, and triglyceride levels in coronary artery disease patients. The Ser447-stop substitution in the lipoprotein lipase gene. REGRESS Study Group. Circulation95, 2628– 2635.
50. Halvatsiotis I., Tsiotra P. C., Ikonomidis I., Kollias A., Mitrou P., Maratou E., et al. 2010 Genetic variation in the adiponectin receptor 2 (ADIPOR2) gene is associated with coronary artery disease and increased ADIPOR2 expression in peripheral monocytes. Cardiovasc. Diabetol.9, 10.
51. Hanson E. S. and Dallman M. F. 1995 Neuropeptide Y (NPY) may integrate responses of hypothalamic feeding systems and the hypothalamo-pituitary-adrenal axis. J. Neuroendocrinol.7, 273–279.
52. Hao K., Bosse Y., Nickle D. C., Pare P. D., Postma D. S., Laviolette M., et al. 2012 Lung eQTLs to help reveal the molecular underpinnings of asthma. PLoS Genet.8, e1003029.
53. He X., Fuller C. K., Song Y., Meng Q., Zhang B., Yang X., et al. 2013 Sherlock: detecting gene-disease associations by matching patterns of expression QTL and GWAS. Am. J. Hum. Genet.92, 667–680.
54. Heidema A. G., Wang P., van Rossum C. T., Feskens E. J., Boer J. M., Bouwman F. G., et al. 2010 Sex-specific effects of CNTF, IL6 and UCP2 polymorphisms on weight gain. Physiol. Behav.99, 1–7.
55. Hernandez-Guerrero C., Monzon-Bordonaba F., Jimenez-Zamudio L., Ahued-Ahued R., Arechavaleta-Velasco F., Strauss J. F. 3., et al. 2003 In-vitro secretion of proinflammatory cytokines by human amniochorion carrying hyper-responsive gene polymorphisms of tumour necrosis factor-alpha and interleukin-1beta. Mol. Hum. Reprod.9, 625–629.
56. Hoffstedt J., Eriksson P., Hellstrom L., Rossner S., Ryden M., and Arner P. 2000 Excessive fat accumulation is associated with the TNF alpha-308 G/A promoter polymorphism in women but not in men. Diabetologia43, 117–120.
57. Hotamisligil G. S. 1999 Mechanisms of TNF-alpha-induced insulin resistance. Exp. Clin. Endocrinol. Diabetes107, 119–125.
58. Hsu L. A., Chang C. J., Wu S., Teng M. S., Chou H. H., Chang H. H., et al. 2010 Association between functional variants of the ICAM1 and CRP genes and metabolic syndrome in Taiwanese subjects. Metabolism59, 1710–1716.
59. Huang A. Q., Hu Y. H., Zhan S. Y., Xu B., Pang Z. C., Cao W. H., et al. 2006 Lipoprotein lipase gene S447X polymorphism modulates the relation between central obesity and serum lipids, a twin study. Int. J. Obes. (Lond.)30, 1693–1701.
60. Hunter K. W. and Crawford N. P. 2008 The future of mouse QTL mapping to diagnose disease in mice in the age of whole-genome association studies. Annu. Rev. Genet.42, 131–141.
61. Huuskonen A., Lappalainen J., Oksala N., Santtila M., Hakkinen K., Kyrolainen H., et al. 2011 Common genetic variation in the IGF1 associates with maximal force output. Med. Sci. Sports Exerc.43, 2368–2374.
62. Ihle J. N., Witthuhn B. A., Quelle F. W., Yamamoto K., and Silvennoinen O. 1995 Signaling through the hematopoietic cytokine receptors. Annu. Rev. Immunol.13, 369–398.
63. Inui A. 1999 Cancer anorexia-cachexia syndrome: are neuropeptides the key. Cancer Res.59, 4493–4501.
64. Ip N. Y., McClain J., Barrezueta N. X., Aldrich T. H., Pan L., Li Y., et al. 1993 The alpha component of the CNTF receptor is required for signaling and defines potential CNTF targets in the adult and during development. Neuron10, 89–102.
65. Irigaray P., Newby J. A., Lacomme S., and Belpomme D. 2007 Overweight/obesity and cancer genesis: more than a biological link. Biomed. Pharmacother.61, 665–678.
66. Iynedjian P. B. 2009 Molecular physiology of mammalian glucokinase. Cell Mol. Life Sci.66, 27–42.
67. Izumiya Y., Hopkins T., Morris C., Sato K., Zeng L., Viereck J., et al. 2008 Fast/glycolytic muscle fiber growth reduces fat mass and improves metabolic parameters in obese mice. Cell Metab.7, 159–172.
68. Jaakkola U., Pesonen U., Vainio-Jylha E., Koulu M., Pollonen M., and Kallio J. 2006 The Leu7Pro polymorphism of neuropeptide Y is associated with younger age of onset of type 2 diabetes mellitus and increased risk for nephropathy in subjects with diabetic retinopathy. Exp. Clin. Endocrinol. Diabetes114, 147–152.
69. Jatoi A., Nguyen P. L., Foster N., Sun D., Stella P. J., Campbell M., et al. 2007 Interleukin-1 genetic polymorphisms and their relationship to the cancer anorexia/weight loss syndrome in metastatic gastric and gastroesophageal junction adenocarcinoma. J. Support Oncol.5, 41–46.
70. Jatoi A., Qi Y., Kendall G., Jiang R., McNallan S., Cunningham J., et al. 2010 The cancer anorexia/weight loss syndrome: exploring associations with single nucleotide polymorphisms (SNPs) of inflammatory cytokines in patients with non-small cell lung cancer. Support Care Cancer18, 1299–1304.
71. Jermendy A., Korner A., Kovacs M., Kaszas E., Balazsovics J., Szocs A., et al. 2010 Association between toll-like receptor polymorphisms and serum levels of tumor necrosis factor-alpha and its soluble receptors in obese children. Med. Sci. Monit.16, 180–185.
72. Jewell C. M. and Cidlowski J. A. 2007 Molecular evidence for a link between the N363S glucocorticoid receptor polymorphism and altered gene expression. J. Clin. Endocrinol. Metab.92, 3268–3277.
73. Jones J. I. and Clemmons D. R. 1995 Insulin-like growth factors and their binding proteins: biological actions. Endocr. Rev.16, 3–34.
74. Kaluza W., Reuss E., Grossmann S., Hug R., Schopf R. E., Galle P. R., et al. 2000 Different transcriptional activity and in vitro TNF-alpha production in psoriasis patients carrying the TNF-alpha 238A promoter polymorphism. J. Invest. Dermatol.114, 1180–1183.
75. Karvonen M. K., Valkonen V. P., Lakka T. A., Salonen R., Koulu M., Pesonen U., et al. 2001 Leucine7 to proline7 polymorphism in the preproneuropeptide Y is associated with the progression of carotid atherosclerosis, blood pressure and serum lipids in Finnish men. Atherosclerosis159, 145–151.
76. Kawai T. and Akira S. 2006 TLR signaling. Cell Death Differ.13, 816–825.
77. Kerem M., Ferahkose Z., Yilmaz U. T., Pasaoglu H., Ofluoglu E., Bedirli A., et al. 2008 Adipokines and ghrelin in gastric cancer cachexia. World J. Gastroenterol.14, 3633–3641.
78. Kim S. F., Huri D. A., and Snyder S. H. 2005 Inducible nitric oxide synthase binds, S-nitrosylates, and activates cyclooxygenase-2. Science310, 1966–1970.
79. Kishimoto T. 2005 Interleukin-6: from basic science to medicine–40 years in immunology. Annu. Rev. Immunol.23, 1–21.
80. Knoll S., Zimmer S., Hinney A., Scherag A., Neubauer A., and Hebebrand J. 2008 Val103Ile polymorphism of the melanocortin-4 receptor gene (MC4R) in cancer cachexia. BMC Cancer8, 85.
81. Kotronen A., Yki-Jarvinen H., Aminoff A., Bergholm R., Pietilainen K. H., Westerbacka J., et al. 2009 Genetic variation in the ADIPOR2 gene is associated with liver fat content and its surrogate markers in three independent cohorts. Eur. J. Endocrinol.160, 593–602.
82. Kozaki K., Gotoda T., Kawamura M., Shimano H., Yazaki Y., Ouchi Y., et al. 1993 Mutational analysis of human lipoprotein lipase by carboxy-terminal truncation. J. Lipid Res.34, 1765–1772.
83. Kusminski C. M., da Silva N. F., Creely S. J., Fisher F. M., Harte A. L., Baker A. R., et al. 2007 The in vitro effects of resistin on the innate immune signaling pathway in isolated human subcutaneous adipocytes. J. Clin. Endocrinol. Metab.92, 270–276.
84. Lai K. M., Gonzalez M., Poueymirou W. T., Kline W. O., Na E., Zlotchenko E., et al. 2004 Conditional activation of akt in adult skeletal muscle induces rapid hypertrophy. Mol. Cell Biol.24, 9295–9304.
85. Lambert P. D., Anderson K. D., Sleeman M. W., Wong V., Tan J., Hijarunguru A., et al. 2001 Ciliary neurotrophic factor activates leptin-like pathways and reduces body fat, without cachexia or rebound weight gain, even in leptin-resistant obesity. Proc. Natl. Acad. Sci. USA98, 4652–4657.
86. Ledesma A., de Lacoba M. G., and Rial E. 2002 The mitochondrial uncoupling proteins. Genome Biol.3, Reviews3015.
87. Legaspi A., Jeevanandam M., Starnes Jr. H. F., and Brennan M. F. 1987 Whole body lipid and energy metabolism in the cancer patient. Metabolism36, 958–963.
88. Lehrke M. and Lazar M. A. 2005 The many faces of PPARgamma. Cell123, 993–999.
89. Li H., Xu R., Peng X., Wang Y., and Wang T. 2013 Association of glucokinase regulatory protein polymorphism with type 2 diabetes and fasting plasma glucose: a meta-analysis. Mol. Biol. Rep.40, 3935–4392.
90. Lind H., Haugen A., and Zienolddiny S. 2007 Differential binding of proteins to the IL1B -31 T/C polymorphism in lung epithelial cells. Cytokine38, 43–48.
91. Loos R. J., Ruchat S., Rankinen T., Tremblay A., Perusse L., and Bouchard C. 2007 Adiponectin and adiponectin receptor gene variants in relation to resting metabolic rate, respiratory quotient, and adiposity-related phenotypes in the Quebec Family Study. Am. J. Clin. Nutr.85, 26–34.
92. Mackevics V., Heid I. M., Wagner S. A., Cip P., Doppelmayr H., Lejnieks A., et al. 2006 The adiponectin gene is associated with adiponectin levels but not with characteristics of the insulin resistance syndrome in healthy Caucasians. Eur. J. Hum. Genet.14, 349–356.
93. Manenschijn L., van den Akker E. L., Lamberts S. W., and van Rossum E. F. 2009 Clinical features associated with glucocorticoid receptor polymorphisms. An overview. Ann. N. Y. Acad. Sci.1179, 179–198.
94. Marcell T. J., McAuley K. A., Traustadottir T., and Reaven P. D. 2005 Exercise training is not associated with improved levels of C-reactive protein or adiponectin. Metabolism54, 533–541.
95. Matsumura K., Tsuchihashi T., Fujii K., Abe I., and Iida M. 2002 Central ghrelin modulates sympathetic activity in conscious rabbits. Hypertension40, 694–699.
96. McArthur J. A., Zhang Q., and Quasney M. W. 2002 Association between the A/A genotype at the lymphotoxin-alpha+250 site and increased mortality in children with positive blood cultures. Pediatr. Crit. Care. Med.3, 341–344.
97. McTernan P. G., Kusminski C. M., and Kumar S. 2006 Resistin. Curr. Opin. Lipidol.17, 170–175.
98. Mead J. R., Irvine S. A., and Ramji D. P. 2002 Lipoprotein lipase: structure, function, regulation, and role in disease. J. Mol. Med.(Berl.)80, 753–769.
99. Miller M. A., Kerry S. M., Dong Y., Strazzullo P., and Cappuccio F. P. 2004 Association between the Thr715Pro P-selectin gene polymorphism and soluble P-selectin levels in a multiethnic population in South London. Thromb. Haemost.92, 1060– 1065.
100. Miller B. S., Ignatoski K. M., Daignault S., Lindland C., Doherty M., Gauger P. G., et al. 2012 Worsening Central Sarcopenia and Increasing Intra-Abdominal Fat Correlate with Decreased Survival in Patients with Adrenocortical Carcinoma. World J. Surg.36, 1509–1516.
101. Mosher D. S., Quignon P., Bustamante C. D., Sutter N. B., Mellersh C. S., Parker H. G., et al. 2007 A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs. PLoS Genet.3, e79.
102. Muscaritoli M., Anker S. D., Argiles J., Aversa Z., Bauer J. M., Biolo G., et al. 2010 Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by Special Interest Groups (SIG) ”cachexia-anorexia in chronic wasting diseases” and ”nutrition in geriatrics. Clin. Nutr.29, 154–159.
103. Nagaev I., Bokarewa M., Tarkowski A., and Smith U. 2006 Human resistin is a systemic immune-derived proinflammatory cytokine targeting both leukocytes and adipocytes. PLoS One1, e31.
104. Ng P. C. and Henikoff S. 2001 Predicting deleterious amino acid substitutions.a. Genome Res.11, 863–874.
105. Ng P. C. and Henikoff S. 2003 SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res.31, 3812–3814.
106. Niskanen L., Karvonen M. K., Valve R., Koulu M., Pesonen U., Mercuri M., et al. 2000 Leucine 7 to proline 7 polymorphism in the neuropeptide Y gene is associated with enhanced carotid atherosclerosis in elderly patients with type 2 diabetes and control subjects. J. Clin. Endocrinol. Metab.85, 2266–2269.
107. Norata G. D., Ongari M., Garlaschelli K., Tibolla G., Grigore L., Raselli S., et al. 2007 Effect of the -420C/G variant of the resistin gene promoter on metabolic syndrome, obesity, myocardial infarction and kidney dysfunction. J. Intern. Med.262, 104–112.
108. Ol K. K., Agachan B., Gormus U., Toptas B., and Isbir T. 2011 Cox-2 gene polymorphism and IL-6 levels in coronary artery disease. Genet. Mol. Res.10, 810–816.
109. Olofsson L. E., Olsson B., Lystig T., Jacobson P., Jernas M., Sjoholm K., et al. 2010 Preliminary report: Zn-alpha2-glycoprotein genotype and serum levels are associated with serum lipids. Metabolism59, 1316–1318.
110. Osawa H., Tabara Y., Kawamoto R., Ohashi J., Ochi M., Onuma H., et al. 2007 Plasma resistin, associated with single nucleotide polymorphism -420, is correlated with insulin resistance, lower HDL cholesterol, and high-sensitivity C-reactive protein in the Japanese general population. Diabetes Care30, 1501–1506.
111. Pallafacchina G., Calabria E., Serrano A. L., Kalhovde J. M., and Schiaffino S. 2002 A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification. Proc. Natl. Acad. Sci. USA99, 9213–9218.
112. Paul P. K. and Kumar A. 2011 TRAF6 coordinates the activation of autophagy and ubiquitin-proteasome systems in atrophying skeletal muscle. Autophagy7, 555–556.
113. Pino-Yanes M., Corrales A., Casula M., Blanco J., Muriel A., Espinosa E., et al. 2010 Common variants of TLR1 associate with organ dysfunction and sustained pro-inflammatory responses during sepsis. PLoS One5, e13759.
114. Plata-Salaman C. R. 2000 Central nervous system mechanisms contributing to the cachexia-anorexia syndrome. Nutrition16, 1009–1012.
115. Plourde M., Vohl M. C., Bellis C., Carless M., Dyer T., Dolley G., et al. 2012 A variant in the LRRFIP1 gene is associated with adiposity and inflammation. Obesity (Silver Spring) (doi: 10.1038/oby.2012.181).
116. Pollin T. I., Damcott C. M., Shen H., Ott S. H., Shelton J., Horenstein R. B., et al. 2008 A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection. Science322, 1702–1705.
117. Prado C. M., Birdsell L. A., and Baracos V. E. 2009 The emerging role of computerized tomography in assessing cancer cachexia. Curr. Opin. Support Palliat. Care3, 269–275.
118. Prado C. M., Sawyer M. B., Ghosh S., Lieffers J. R., Esfandiari N., Antoun S., et al. 2013 Central tenet of cancer cachexia therapy: Do patients with advanced cancer have exploitable anabolic potential? Am. J. Clin. Nutr.98, 1012–1019.
119. Pratt W. B., Morishima Y., Murphy M., and Harrell M. 2006 Chaperoning of glucocorticoid receptors. Handb. Exp. Pharmacol.172, 111–138.
120. Punzi T., Fabris A., Morucci G., Biagioni P., Gulisano M., Ruggiero M., et al. 2012 C-reactive protein levels and vitamin d receptor polymorphisms as markers in predicting cachectic syndrome in cancer patients. Mol. Diagn. Ther.16, 115–124.
121. Quinn L. S., Anderson B. G., Drivdahl R. H., Alvarez B., and Argiles J. M. 2002 Overexpression of interleukin-15 induces skeletal muscle hypertrophy in vitro: implications for treatment of muscle wasting disorders. Exp. Cell Res.280, 55–63.
122. Rausch S. M., Clark M. M., Patten C., Liu H., Felten S., Li Y., et al. 2010 Relationship between cytokine gene single nucleotide polymorphisms and symptom burden and quality of life in lung cancer survivors. Cancer116, 4103–4113.
123. Ray A. and Prefontaine K. E. 1994 Physical association and functional antagonism between the p65 subunit of transcription factor NF-kappa B and the glucocorticoid receptor. Proc. Natl. Acad. Sci. USA91, 752–756.
124. Reue K. 2009 The lipin family: mutations and metabolism. Curr. Opin. Lipidol.20, 165–170.
125. Ridker P. M., Pare G., Parker A., Zee R. Y., Danik J. S., Buring J. E., et al. 2008 Loci related to metabolic-syndrome pathways including LEPR, HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women’s Genome Health Study. Am. J. Hum. Genet.82, 1185–1192.
126. Robert F., Mills J. R., Agenor A., Wang D., DiMarco S., Cencic R., et al. 2012 Targeting protein synthesis in a Myc/mTOR-driven model of anorexia-cachexia syndrome delays its onset and prolongs survival. Cancer Res.72, 747–756.
127. Rommel C., Bodine S. C., Clarke B. A., Rossman R., Nunez L., Stitt T. N., et al. 2001 Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nat. Cell Biol.3, 1009–1013.
128. Roth S. M., Schrager M. A., Ferrell R. E., Riechman S. E., Metter E. J., Lynch N. A., et al. 2001 CNTF genotype is associated with muscular strength and quality in humans across the adult age span. J. Appl. Physiol.90, 1205–1210.
129. Roth S. M., Schrager M. A., Lee M. R., Metter E. J., Hurley B. F., and Ferrell R. E. 2003 Interleukin-6 (IL6) genotype is associated with fat-free mass in men but not women. J. Gerontol. A Biol. Sci. Med. Sci.58, 1085–1088.
130. Roussel R., Reis A. F., Dubois-Laforgue D., Bellanne-Chantelot C., Timsit J., and Velho G. 2003 The N363S polymorphism in the glucocorticoid receptor gene is associated with overweight in subjects with type 2 diabetes mellitus. Clin. Endocrinol. (Oxf.)59, 237–241.
131. Russcher H., Smit P., van den Akker E. L., van Rossum E. F., Brinkmann A. O., de Jong F. H., et al. 2005 Two polymorphisms in the glucocorticoid receptor gene directly affect glucocorticoid-regulated gene expression. J. Clin. Endocrinol. Metab.90, 5804–5810.
132. Russell S. T., Hirai K., and Tisdale M. J. 2002 Role of beta3-adrenergic receptors in the action of a tumour lipid mobilizing factor. Br. J. Cancer86, 424–428.
133. Sallakci N., Akcurin G., Koksoy S., Kardelen F., Uguz A., Coskun M., et al. 2005 TNF-alpha G-308A polymorphism is associated with rheumatic fever and correlates with increased TNF-alpha production. J. Autoimmun.25, 150–154.
134. Sandri M., Sandri C., Gilbert A., Skurk C., Calabria E., Picard A., et al. 2004 Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell117, 399–412.
135. Sartori R., Milan G., Patron M., Mammucari C., Blaauw B., Abraham R., et al. 2009 Smad2 and 3 transcription factors control muscle mass in adulthood. Am. J. Physiol. Cell Physiol.296, C1248–1257.
136. Schadt E. E., Molony C., Chudin E., Hao K., Yang X., Lum P. Y., et al. 2008 Mapping the genetic architecture of gene expression in human liver. PLoS Biol.6, e107.
137. Sharma S., Sharma A., Kumar S., Sharma S. K., and Ghosh B. 2006 Association of TNF haplotypes with asthma, serum IgE levels, and correlation with serum TNF-alpha levels. Am. J. Respir. Cell Mol. Biol.35, 488–495.
138. Shibata M., Nezu T., Takekawa M., Takizawa H., Ando K., Miyake H., et al. 1996 Serum levels of interleukin-10 and interleukin-12 in patients with colorectal cancer. Ann. N. Y. Acad. Sci.795, 410–412.
139. Shimura T., Hagihara M., Takebe K., Munkhbat B., Odaka T., Kato H., et al. 1994 The study of tumor necrosis factor beta gene polymorphism in lung cancer patients. Cancer73, 1184–1188.
140. Shimura T., Hagihara M., Takebe K., Munkhbat B., Ogoshi K., Mitomi T., et al. 1995 10.5-kb homozygote of tumor necrosis factor-beta gene is associated with a better prognosis in gastric cancer patients. Cancer75, 1450–1453.
141. Silswal N., Singh A. K., Aruna B., Mukhopadhyay S., Ghosh S., and Ehtesham N. Z. 2005 Human resistin stimulates the pro-inflammatory cytokines TNF-alpha and IL-12 in macrophages by NF-kappaB-dependent pathway. Biochem. Biophys. Res. Commun.334, 1092–1101.
142. Siren P. M. and Siren M. J. 2010 Systemic zinc redistribution and dyshomeostasis in cancer cachexia. J. Cachexia Sarcopenia Muscle1, 23–33.
143. Skoog T., van’t Hooft F. M., Kallin B., Jovinge S., Boquist S., Nilsson J., et al. 1999 A common functional polymorphism (C– >A substitution at position -863) in the promoter region of the tumour necrosis factor-alpha (TNF-alpha) gene associated with reduced circulating levels of TNF-alpha. Hum. Mol. Genet.8, 1443–1449.
144. Solheim T. S., Fayers P. M., Fladvad T., Tan B., Skorpen F., Fearon K., et al. 2011 Is there a genetic cause for cancer cachexia? - a clinical validation study in 1797 patients. Br. J. Cancer105, 1244–1251.
145. Solheim T. S., Fayers P. M., Fladvad T., Tan B., Skorpen F., Fearon K., et al. 2012 Is there a genetic cause of appetite loss?-an explorative study in 1,853 cancer patients. J. Cachexia Sarcopenia Muscle3, 191–198.
146. Song G., Ouyang G., and Bao S. 2005 The activation of Akt/PKB signaling pathway and cell survival. J. Cell Mol. Med.9, 59–71.
147. Stancakova A., Civelek M., Saleem N. K., Soininen P., Kangas A. J., Cederberg H., et al. 2012 Hyperglycemia and a common variant of GCKR are associated with the levels of eight amino acids in 9,369 Finnish men. Diabetes61, 1895–1902.
148. Stephens N. A., Skipworth R. J., and Fearon K. C. 2008 Cachexia, survival and the acute phase response. Curr. Opin. Support Palliat. Care2, 267–274.
149. Stewart G. D., Skipworth R. J., and Fearon K. C. 2006 Cancer cachexia and fatigue. Clin. Med.6, 140–143.
150. Strandberg L., Lorentzon M., Hellqvist A., Nilsson S., Wallenius V., Ohlsson C., et al. 2006 Interleukin-1 system gene polymorphisms are associated with fat mass in young men. J. Clin. Endocrinol. Metab.91, 2749–2754.
151. Stuber F., Petersen M., Bokelmann F., and Schade U. 1996 A genomic polymorphism within the tumor necrosis factor locus influences plasma tumor necrosis factor-alpha concentrations and outcome of patients with severe sepsis. Crit. Care Med.24, 381–384.
152. Sun F., Sun Y., Yu Z., Zhang D., Zhang J., Song B., et al. 2010a Interleukin-10 gene polymorphisms influence susceptibility to cachexia in patients with low-third gastric cancer in a Chinese population. Mol. Diagn. Ther.14, 95–100.
153. Sun F., Sun Y., Zhang D., Zhang J., Song B., and Zheng H. 2010b Association of interleukin-10 gene polymorphism with cachexia in Chinese patients with gastric cancer. Ann. Clin. Lab Sci.40, 149–155.
154. Tabor H. K., Risch N. J., and Myers R. M. 2002 Candidate-gene approaches for studying complex genetic traits: practical considerations. Nat. Rev. Genet.3, 391–397.
155. Tan B. H. and Fearon K. C. 2010 Cytokine gene polymorphisms and susceptibility to cachexia. Curr. Opin. Support Palliat. Care4, 243–248.
156. Tan B. H., Birdsell L. A., Martin L., Baracos V. E., and Fearon K. C. 2009 Sarcopenia in an overweight or obese patient is an adverse prognostic factor in pancreatic cancer. Clin. Cancer Res.15, 6973–6979.
157. Tan B. H., Ross J. A., Kaasa S., Skorpen F., and Fearon K. C. 2011 Identification of possible genetic polymorphisms involved in cancer cachexia: a systematic review. J. Genet.90, 165–177.
158. Tan B. H., Fladvad T., Braun T. P., Vigano A., Strasser F., Deans D. A., et al. 2012 P-selectin genotype is associated with the development of cancer cachexia. EMBO Mol. Med.4, 462– 471.
159. Teng A. C., Adamo K., Tesson F., and Stewart A. F. 2009 Functional characterization of a promoter polymorphism that drives ACSL5 gene expression in skeletal muscle and associates with diet-induced weight loss. FASEB J.23, 1705–1709.
160. Thair S. A., Walley K. R., Nakada T. A., McConechy M. K., Boyd J. H., Wellman H., et al. 2011 A single nucleotide polymorphism in NF-kappaB inducing kinase is associated with mortality in septic shock. J. Immunol.186, 2321–2328.
161. Thompson S. R., McCaskie P. A., Beilby J. P., Hung J., Jennens M., Chapman C., et al. 2007 IL18 haplotypes are associated with serum IL-18 concentrations in a population-based study and a cohort of individuals with premature coronary heart disease. Clin. Chem.53, 2078–2085.
162. Tisdale M. J. 2002 Cachexia in cancer patients. Nat. Rev. Cancer2, 862–871.
163. Tolusso B., Pietrapertosa D., Morelli A., De Santis M., Gremese E., Farina G., et al. 2006 IL-1B and IL-1RN gene polymorphisms in rheumatoid arthritis: relationship with protein plasma levels and response to therapy. Pharmacogenomics7, 683–695.
164. Torra I. P., Chinetti G., Duval C., Fruchart J. C., and Staels B. 2001 Peroxisome proliferator-activated receptors: from transcriptional control to clinical practice. Curr. Opin. Lipidol.12, 245–254.
165. Toshinai K., Date Y., Murakami N., Shimada M., Mondal M. S., Shimbara T., et al. 2003 Ghrelin-induced food intake is mediated via the orexin pathway. Endocrinology144, 1506–1512.
166. Trendelenburg A. U., Meyer A., Rohner D., Boyle J., Hatakeyama S., and Glass D. J. 2009 Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size. Am. J. Physiol. Cell Physiol.296, C1258–1270.
167. Trinchieri G. and Sher A. 2007 Cooperation of Toll-like receptor signals in innate immune defence. Nat. Rev. Immunol.7, 179–190.
168. van Raalte D. H., van Leeuwen N., Simonis-Bik A. M., Nijpels G., van Haeften T. W., Schafer S. A., et al. 2012 Glucocorticoid receptor gene polymorphisms are associated with reduced first-phase glucose-stimulated nsulin secretion and disposition index in women, but not in men. Diabet Med.9, e211–216.
169. van Rijn B. B., Franx A., Steegers E. A., de Groot C. J., Bertina R. M., Pasterkamp G., et al. 2008 Maternal TLR4 and NOD2 gene variants, pro-inflammatory phenotype and susceptibility to early-onset preeclampsia and HELLP syndrome. PLoS One3, e1865.
170. Van Schaftingen E. 1994 Short-term regulation of glucokinase. Diabetologia37suppl 2, 43–47.
171. Vaxillaire M., Dechaume A., Vasseur-Delannoy V., Lahmidi S., Vatin V., Lepretre F., et al. 2006 Genetic analysis of ADIPOR1 and ADIPOR2 candidate polymorphisms for type 2 diabetes in the Caucasian population. Diabetes55, 856–861.
172. Verheus M., McKay J. D., Kaaks R., Canzian F., Biessy C., Johansson M., et al. 2008 Common genetic variation in the IGF-1 gene, serum IGF-I levels and breast density. Breast Cancer Res. Treat.112, 109–122.
173. Volcik K. A., Ballantyne C. M., Coresh J., Folsom A. R., Wu K. K., and Boerwinkle E. 2006 P-selectin Thr715Pro polymorphism predicts P-selectin levels but not risk of incident coronary heart disease or ischemic stroke in a cohort of 14595 participants: the Atherosclerosis Risk in Communities Study. Atherosclerosis186, 74–79.
174. von Haehling S., Lainscak M., Springer J., and Anker S. D. 2009 Cardiac cachexia: a systematic overview. Pharmacol Ther.121, 227–252.
175. von Kugelgen I. 2006 Pharmacological profiles of cloned mammalian P2Y-receptor subtypes. Pharmacol. Ther.110, 415–432.
176. Wen A. Q., Wang J., Feng K., Zhu P. F., Wang Z. G., and Jiang J. X. 2006 Effects of haplotypes in the interleukin 1beta promoter on lipopolysaccharide-induced interleukin 1beta expression. Shock26, 25–30.
177. Weyrich P., Staiger H., Stancakova A., Machicao F., Machann J., Schick F., et al. 2010 The D299G/T399I Toll-like receptor 4 variant associates with body and liver fat: results from the TULIP and METSIM Studies. PLoS One5, e13980.
178. Wilker E. H., Alexeeff S. E., Poon A., Litonjua A. A., Sparrow D., Vokonas P. S., et al. 2009 Candidate genes for respiratory disease associated with markers of inflammation and endothelial dysfunction in elderly men. Atherosclerosis206, 480– 485.
179. Wilson A. G., Symons J. A., McDowell T. L., McDevitt H. O., and Duff G. W. 1997 Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc. Natl. Acad. Sci. USA94, 3195–3199.
180. Wjst M. 2004 Target SNP selection in complex disease association studies. BMC Bioinformatics5, 92.
181. Wurfel M. M., Gordon A. C., Holden T. D., Radella F., Strout J., Kajikawa O., et al. 2008 Toll-like receptor 1 polymorphisms affect innate immune responses and outcomes in sepsis. Am. J. Respir. Crit. Care Med.178, 710–720.
182. Yamauchi T., Kamon J., Ito Y., Tsuchida A., Yokomizo T., Kita S., et al. 2003 Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature423, 762–769.
183. Yang X., Jansson P. A., Pellme F., Laakso M., and Smith U. 2005 Effect of the interleukin-6 (-174) g/c promoter polymorphism on adiponectin and insulin sensitivity. Obes. Res.13, 813–817.
184. Zhang D., Zheng H., Zhou Y., Tang X., Yu B., and Li J. 2007 Association of IL-1beta gene polymorphism with cachexia from locally advanced gastric cancer. BMC Cancer7, 45.
185. Zhang D., Zhou Y., Wu L., Wang S., Zheng H., Yu B., et al. 2008 Association of IL-6 gene polymorphisms with cachexia susceptibility and survival time of patients with pancreatic cancer. Ann. Clin. Lab. Sci.38, 113–119.
186. Zhu H. J., Dong C. X., Pan H., Ping X. C., Li N. S., Dai Y. F., et al. 2012 rs4215 SNP in zinc-alpha2-glycoprotein gene is associated with obesity in Chinese north Han population. Gene.