Genetic Epidemiology of Obesity and Cancer

  • Courtney Gray-McGuire
  • Indra Adrianto
  • Thuan Nguyen
  • Chee Paul Lin
Part of the Energy Balance and Cancer book series (EBAC, volume 2)


To understand the genetic epidemiology of obesity and cancer means to consider the genetics of not only these two complex diseases but also the many risk factors associated with them and the molecular mechanisms likely to contribute to their underlying etiology. It is therefore the purpose of this chapter to highlight the following: genetic mapping studies that have been done to isolate genes related to obesity, genetic studies aimed to identify genes for obesity risk factors, and, finally, a discussion of the genes shared across or among the studies of obesity and/or its risk factors and the various cancers. This is by no means an exhaustive discussion as these are each complex traits with complex molecular mechanisms. It is, however, intended to be an overview of the genes likely to be involved in the cascade of pathways linking obesity and cancer.

It is well known that obesity continues to be a leading public health concern not only in the United States but now worldwide. From 1980 to 2002, the prevalence of obesity doubled in adults aged over 20 and overweight prevalence tripled in children and adolescents aged 6–9 years. The estimates of overweight and obesity in 2003–2004 showed that 17.1% of US children and adolescents were overweight and 32.2% of adults were obese [143].

The increasing rates of obesity among children are especially alarming and suggest continuing increases in the rates of obesity-related cancers. Since being overweight in childhood predicts obesity in adulthood [208], obesity occurring in childhood may operate as a ‘cumulative’ exposure that influences cancer risk in later life. Obese children may be subject to potentially long periods of hormonal exposures that operate during adolescence to influence propensity to neoplastic diseases. In females, childhood obesity may also affect the levels of sex hormone at adolescence. A prospective study of 55-year follow-up on 508 adolescents at 13–18 years from Harvard Growth Study showed that overweight adolescent boys had a nine-fold increased risk of colorectal cancer mortality [161]. Associations between adolescent weight and cancer persisted even after adjusting for adult BMI.

A 50-year follow-up of >2,000 British children showed an overall 9% increase in cancer incidence per standard deviation increase in BMI, with effects three times larger for smoking-related cancers. There is also evidence from an Israeli case–control study which indicated that being in the upper quartile of BMI at age 18 years was associated with a 42% increase for ovarian cancer [24]. However, the mechanisms underlying the association between childhood obesity and cancer are not well understood, particularly in conjunction with genetic data. In one case–control study of 40 obese and 40 non-obese prepubertal children, the obese group showed higher levels of IGF-1, insulin, and lower sex-binding hormone than that of the non-obese group [182]. This suggests that high levels of growth factors and altered sex hormone profiles are present in obese children and the exposures to an adverse metabolic milieu may begin early in life.


Obstructive Sleep Apnea Sleep Apnea Sedentary Behavior Obstructive Sleep Apnea Syndrome Sleep Deprivation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Abbott B, Abolins M, Abramov V, Acharya BS, Adams DL, Adams M, Ahn S, Akimov V, Alves GA, Amos N and others (2000). Measurement of the W–>taunu production cross section in pp collisions at square root s=1.8 TeV. Phys Rev Lett, 84(25):5710–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Abnet CC, Freedman ND, Hollenbeck AR, Fraumeni JF, Jr., Leitzmann M, Schatzkin A (2008). A prospective study of BMI and risk of oesophageal and gastric adenocarcinoma. Eur J Cancer, 44(3):465–71.PubMedCrossRefGoogle Scholar
  3. 3.
    Abraham MR, Olson LJ, Joyner MJ, Turner ST, Beck KC, Johnson BD (2002). Angiotensin-converting enzyme genotype modulates pulmonary function and exercise capacity in treated patients with congestive stable heart failure. Circulation, 106(14):1794–9.PubMedCrossRefGoogle Scholar
  4. 4.
    ACS (2008). Cancer Facts and Figures 2008. American Cancer Society.Google Scholar
  5. 5.
    Ahmetov, II, Mozhayskaya IA, Flavell DM, Astratenkova IV, Komkova AI, Lyubaeva EV, Tarakin PP, Shenkman BS, Vdovina AB, Netreba AI and others (2006). PPARalpha gene variation and physical performance in Russian athletes. Eur J Appl Physiol, 97(1):103–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Allen NE, Key TJ, Dossus L et al. (2008). Endogenous sex hormones and endometrail cancer risk in women in the European Prospective Investigation into cancer and Nutrion (EPIC). Endocr Relat Cancer, 15:485–497.PubMedCrossRefGoogle Scholar
  7. 7.
    Alvarez R, Terrados N, Ortolano R, Iglesias-Cubero G, Reguero JR, Batalla A, Cortina A, Fernandez-Garcia B, Rodriguez C, Braga S and others (2000). Genetic variation in the renin-angiotensin system and athletic performance. Eur J Appl Physiol, 82(1–2):117–20.PubMedCrossRefGoogle Scholar
  8. 8.
    Amir O, Amir R, Yamin C, Attias E, Eynon N, Sagiv M, Meckel Y (2007). The ACE deletion allele is associated with Israeli elite endurance athletes. Exp Physiol, 92(5):881–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Atkinson RL, Dhurandhar NV, Allison DB, Bowen RL, Israel BA, Albu JB, Augustus AS (2005). Human adenovirus-36 is associated with increased body weight and paradoxical reduction of serum lipids. Int J Obes (Lond), 29(3):281–6.CrossRefGoogle Scholar
  10. 10.
    Ayas NT, White DP, Al-Delaimy WK, Manson JE, Stampfer MJ, Speizer FE, Patel S, Hu FB (2003). A prospective study of self-reported sleep duration and incident diabetes in women. Diabetes Care, 26(2):380–4.PubMedCrossRefGoogle Scholar
  11. 11.
    Barker DJ, Winter PD, Osmond C, Phillips DI, Sultan HY (1995). Weight gain in infancy and cancer of the ovary. Lancet, 345(8957):1087–1088.PubMedCrossRefGoogle Scholar
  12. 12.
    Becker HF, Jerrentrup A, Ploch T, Grote L, Penzel T, Sullivan CE, Peter JH (2003). Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea. Circulation, 107(1):68–73.PubMedCrossRefGoogle Scholar
  13. 13.
    Berstein LM IE, Kovalevskij AJ, et al. (2004). CYP17 and CYP19 genetic polymorphisms in endometrail cancer: association with intratumoral aromatase activity. Cancer Lett, 207:191–196.PubMedCrossRefGoogle Scholar
  14. 14.
    Bouchard C, Perusse L, Leblanc C (1990). Using MZ twins in experimental research to test for the presence of a genotype-environment interaction effect. Acta Genet Med Gemellol (Roma), 39(1):85–9.Google Scholar
  15. 15.
    Bradbury J (1997). Leptin deficiency linked to human obesity at last. Lancet, 349 (9069):1889.Google Scholar
  16. 16.
    Bray MS, Hagberg JM, Perusse L, Rankinen T, Roth SM, Wolfarth B, Bouchard C (2009). The human gene map for performance and health-related fitness phenotypes: the 2006–2007 update. Med Sci Sports Exerc, 41(1):35–73.PubMedCrossRefGoogle Scholar
  17. 17.
    Bruning PF, Bonfrèr JM, Hart AA, van Noord PA, van der Hoeven H, Collette HJ, Battermann JJ, Jong-Bakker M, Nooijen WJ, de Waard F (1992a). Body Measurements, estrogen availability and the risk of human breast cancer, A case-control study. Int J Cancer, 51:14–19.PubMedCrossRefGoogle Scholar
  18. 18.
    Bruning PF, Bonfrèr JM, van Noord PA, Hart AA, Jong-Bakker M, Nooijen WJ (1992b). Insulin resistance and breast-cancer risk. Int J Cancer, 52:511–516.PubMedCrossRefGoogle Scholar
  19. 19.
    Bruning PF, Van Doorn J, Bonfrer JM, van Noord PA, Korse CM, Linders TC, Hart AA (1995). Insulin-like growth-factor-binding protein 3 is decreased in early-stage operable pre-menopausal breast cancer. Int J Cancer, 62:266–270.PubMedCrossRefGoogle Scholar
  20. 20.
    Brunning PF (1987). Endogenous estrogens and breast cancer a possible relationship between body fat distribution and estrogen availability. J Steroid Biochem, 27:487–492.CrossRefGoogle Scholar
  21. 21.
    Busquets X, Barbe F, Barcelo A, de la Pena M, Sigritz N, Mayoralas LR, Ladaria A, Agusti A (2004). Decreased plasma levels of orexin-A in sleep apnea. Respiration, 71(6):575–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Calle EE, Kaaks R (2004). Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer, 4(1):579–591.PubMedCrossRefGoogle Scholar
  23. 23.
    Carling D (2004). The AMP-activated protein kinase cascade-a unifiying system for energy control. TRENDS Biochem Sci, 29(1):18–24.PubMedCrossRefGoogle Scholar
  24. 24.
    Carskadon MA, Wolfson AR, Acebo C, Tzischinsky O, Seifer R (1998). Adolescent sleep patterns, circadian timing, and sleepiness at a transition to early school days. Sleep, 21(8):871–81.PubMedGoogle Scholar
  25. 25.
    Cecil JE, Tavendale R, Watt P, Hetherington MM, Palmer CN (2008). An obesity-associated FTO gene variant and increased energy intake in children. N Engl J Med, 359(24):2558–66.PubMedCrossRefGoogle Scholar
  26. 26.
    Chan JM, Stampfer MJ, Giovannucci E, Gann PH, Ma J, Wilkinson P, Hennekens CH, Pollak M (1998). Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science, 279(5350):563–566.PubMedCrossRefGoogle Scholar
  27. 27.
    Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, Richardson JA, Williams SC, Xiong Y, Kisanuki Y and others (1999). Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell, 98(4):437–51.PubMedCrossRefGoogle Scholar
  28. 28.
    Chen H, Charlat O, Tartaglia LA, Woofe EA, Weng X, Ellis SJ, Lakey ND, et al. (1996). Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell, 84:491–495.PubMedCrossRefGoogle Scholar
  29. 29.
    Chokkalingam AP, Stanczyk FZ, Reichardt JKV, Hsing AW (2007). Molecular epidemiology of prostate cancer: hormone-related genetic loci. Front Biosci, 12:3436–3446.Google Scholar
  30. 30.
    Chu LW, Reichardt JK, Hsing AW (2008). Androgens and the molecular epidemiology of prostate cancer. Curr Opin Endocrinol Diabetes Obes, 15:261–270.PubMedCrossRefGoogle Scholar
  31. 31.
    Chua SC Jr., Chung WK, Wu-Peng XS, Zhang Y, Liu SM, Tartaglia LA, Leibel RL (1996). Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor. Science, 271:994–996.PubMedCrossRefGoogle Scholar
  32. 32.
    Cirelli C, Gutierrez CM, Tononi G (2004). Extensive and divergent effects of sleep and wakefulness on brain gene expression. Neuron, 41(1):35–43.PubMedCrossRefGoogle Scholar
  33. 33.
    Clayton SJ, May FEB, Westley BR (1997). Insulin-like growth factors control the regulation of oestrogen and progesterone receptor expression by oestrogens. Mol Cell Endocrinol, 128:57–68.PubMedCrossRefGoogle Scholar
  34. 34.
    Collins M, Xenophontos SL, Cariolou MA, Mokone GG, Hudson DE, Anastasiades L, Noakes TD (2004). The ACE gene and endurance performance during the South African Ironman Triathlons. Med Sci Sports Exerc, 36(8):1314–20.PubMedCrossRefGoogle Scholar
  35. 35.
    Cone RD (2005). Anatomy and regulation of the central melanocortin system. Nat Neurosci, 8(5):571–578.PubMedCrossRefGoogle Scholar
  36. 36.
    Coschigano KT, Clemmons D, Bellush LL, Kopchick JJ (2000). Assessment of growth parameters and life span of GHR/BP gene-disrupted mice. Endocrinology, 141(7):2608–2613.PubMedCrossRefGoogle Scholar
  37. 37.
    Coulston AM, Boushey CJ (2008). Nutrition in the Prevention and Treatment of Disease: Academic Press, San Diego, CA.Google Scholar
  38. 38.
    Coyle YM (2009). Lifestyle, Genes, and Cancer. Methods of Molecular Biology, Cancer Epidemiol, 472:25–56.CrossRefGoogle Scholar
  39. 39.
    Dahmen N, Bierbrauer J, Kasten M (2001). Increased prevalence of obesity in narcoleptic patients and relatives. Eur Arch Psychiatry Clin Neurosci, 251(2):85–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Davies RJ, Ali NJ, Stradling JR (1992). Neck circumference and other clinical features in the diagnosis of the obstructive sleep apnoea syndrome. Thorax, 47(2):101–5.PubMedCrossRefGoogle Scholar
  41. 41.
    Defoor J, Martens K, Zielinska D, Matthijs G, Van Nerum H, Schepers D, Fagard R, Vanhees L (2006). The CAREGENE study: polymorphisms of the beta1-adrenoceptor gene and aerobic power in coronary artery disease. Eur Heart J, 27(7):808–16.PubMedCrossRefGoogle Scholar
  42. 42.
    Del Giuduce ME, Fantus IG, Ezzat S, McKeown-Eyssen G, Page D, Goodwin PJ (1998). Insulin and related factors in premenopausal breast cancer risk. Breast Cancer Res Treat, 47:111–120.CrossRefGoogle Scholar
  43. 43.
    DeLellis K, Rinaldi S, Kaaks RJ, Kolonel LN, Henderson B, Le ML (2004). Dietary and lifestyle correlates of plasma insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3): the multiethnic cohort. Cancer Epidemiol Biomarkers Prev, 13(9):1444–1451.PubMedGoogle Scholar
  44. 44.
    Dhurandhar NV, Israel BA, Kolesar JM, Mayhew GF, Cook ME, Atkinson RL (2000). Increased adiposity in animals due to a human virus. Int J Obes Relat Metab Disord, 24(8):989–96.PubMedCrossRefGoogle Scholar
  45. 45.
    Dhurandhar NV, Kulkarni PR, Ajinkya SM, Sherikar AA, Atkinson RL (1997). Association of adenovirus infection with human obesity. Obes Res, 5(5):464–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Dhurandhar NV, Whigham LD, Abbott DH, Schultz-Darken NJ, Israel BA, Bradley SM, Kemnitz JW, Allison DB, Atkinson RL (2002). Human adenovirus Ad-36 promotes weight gain in male rhesus and marmoset monkeys. J Nutr, 132(10):3155–60.PubMedGoogle Scholar
  47. 47.
    Dina C, Meyre D, Gallina S, Durand E, Korner A, Jacobson P, Carlsson LM, Kiess W, Vatin V, Lecoeur C and others (2007). Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet, 39(6):724–6.PubMedCrossRefGoogle Scholar
  48. 48.
    Dinges DF, Pack F, Williams K, Gillen KA, Powell JW, Ott GE, Aptowicz C, Pack AI (1997). Cumulative sleepiness, mood disturbance, and psychomotor vigilance performance decrements during a week of sleep restricted to 4–5 hours per night. Sleep, 20(4):267–77.PubMedGoogle Scholar
  49. 49.
    Dong C, Li WD, Li D, Price RA (2005). Interaction between obesity-susceptibility loci in chromosome regions 2p25-p24 and 13q13-q21. Eur J Hum Genet, 13(1):102–108.Google Scholar
  50. 50.
    Dong C, Wang S, Li WD, Li D, Zhao H, Price RA (2003). Interacting genetic loci on chromosomes 20 and 10 influence extreme human obesity. Am J Hum Genet, 72(1):115–124.PubMedCrossRefGoogle Scholar
  51. 51.
    Engeland A, Tretli S, Bjorge T (2004). Height and body mass index in relation to esophageal cancer; 23-year follow-up of two million Norwegian men and women. Cancer Causes Control, 15(8):837–43.PubMedCrossRefGoogle Scholar
  52. 52.
    Espana RA, McCormack SL, Mochizuki T, Scammell TE (2007). Running promotes wakefulness and increases cataplexy in orexin knockout mice. Sleep, 30(11):1417–25.PubMedGoogle Scholar
  53. 53.
    Evans DJ, Hoffmann RG, Kalkhoff RK, Kissebah AH (1984). Relationship of body fat topography to insulin sensitivity and metabolic profiles in premenopausal women. Metabolism, 33:68–75.PubMedCrossRefGoogle Scholar
  54. 54.
    Faccenda JF, Mackay TW, Boon NA, Douglas NJ (2001). Randomized placebo-controlled trial of continuous positive airway pressure on blood pressure in the sleep apnea-hypopnea syndrome. Am J Respir Crit Care Med, 163(2):344–8.PubMedGoogle Scholar
  55. 55.
    Frayling TM (2007). Genome-wide association studies provide new insights into type 2 diabetes aetiology. Nat Rev Genet, 8(9):657–62.PubMedCrossRefGoogle Scholar
  56. 56.
    Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW and others (2007). A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science, 316(5826):889–94.PubMedCrossRefGoogle Scholar
  57. 57.
    Freedman ND, Ahn J, Hou L, Lissowska J, Zatonski W, Yeager M, Chanock SJ, Chow WH, Abnet CC (2008). Polymorphisms in estrogen- and androgen- metabolizing genes and the risk of gastric cancer. Carcinogenesis, 30(1):71–77.PubMedCrossRefGoogle Scholar
  58. 58.
    Gascon F, Valle M, Martos R, Zafra M, Morales R, Castano MA (2004). Childhood obesity and hormonal abnormalities associated with cancer risk. Eur J Cancer Prev, 13(3):193–197.Google Scholar
  59. 59.
    Gayagay G, Yu B, Hambly B, Boston T, Hahn A, Celermajer DS, Trent RJ (1998). Elite endurance athletes and the ACE I allele – the role of genes in athletic performance. Hum Genet, 103(1):48–50.PubMedCrossRefGoogle Scholar
  60. 60.
    Giovannucci E, Pollak MN, Platz EA, Willett WC, Stampfer MJ, Majeed N, Colditz GA, Speizer FE, Hankinson SE (2000). A prospective study of plasma insulin-like growth factor-1 and binding protein-3 and risk of colorectal neoplasia in women. Cancer Epidemiol Biomarkers Prev, 9(4):345–349.PubMedGoogle Scholar
  61. 61.
    Gloria W (2003). Basic Geriatric Nursing: Elsevier Health Sciences, St. Louis, Mo.Google Scholar
  62. 62.
    Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Madarnas Y, Hartwick W, Hoffman B, Hood N (2002). Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol, 20(1):42–51.PubMedCrossRefGoogle Scholar
  63. 63.
    Gortmaker SL, Must A, Sobol AM, Peterson K, Colditz GA, Dietz WH (1996). Television viewing as a cause of increasing obesity among children in the United States, 1986–1990. Arch Pediatr Adolesc Med, 150(4):356–62.PubMedCrossRefGoogle Scholar
  64. 64.
    Gottlieb DJ, Punjabi NM, Newman AB, Resnick HE, Redline S, Baldwin CM, Nieto FJ (2005). Association of sleep time with diabetes mellitus and impaired glucose tolerance. Arch Intern Med, 165(8):863–7.PubMedCrossRefGoogle Scholar
  65. 65.
    Group. TEHaBCC (2002). Endogenous sex hormones and breast cancer in postmenopausal women, reanalysis of nine prospective studies. J Natl Cancer Inst, 94:606–616.Google Scholar
  66. 66.
    Guilleminault C, Partinen M, Hollman K, Powell N, Stoohs R (1995). Familial aggregates in obstructive sleep apnea syndrome. Chest, 107(6):1545–51.PubMedCrossRefGoogle Scholar
  67. 67.
    Haffner SM, Katz MS, Stern MP, Dunn JF (1989). Relationship of sex hormone binding globulin to overall adiposity and body fat distribution in a biethnic population. Int J Obes, 13:1–9.PubMedGoogle Scholar
  68. 68.
    Hagberg JM, Ferrell RE, McCole SD, Wilund KR, Moore GE (1998). VO2 max is associated with ACE genotype in postmenopausal women. J Appl Physiol, 85(5):1842–6.PubMedGoogle Scholar
  69. 69.
    Hagberg JM, McCole SD, Brown MD, Ferrell RE, Wilund KR, Huberty A, Douglass LW, Moore GE (2002). ACE insertion/deletion polymorphism and submaximal exercise hemodynamics in postmenopausal women. J Appl Physiol, 92(3):1083–8.PubMedGoogle Scholar
  70. 70.
    Hankinson SE, Willett WC, Colditz GA, Hunter DJ, Michaud DS, Deroo B, Rosner B, Speizer FE, Pollak M (1998). Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet, 351(9113):1393–1396.PubMedCrossRefGoogle Scholar
  71. 71.
    Hara J, Yanagisawa M, Sakurai T (2005a). Difference in obesity phenotype between orexin-knockout mice and orexin neuron-deficient mice with same genetic background and environmental conditions. Neurosci Lett, 380(3):239–42.PubMedCrossRefGoogle Scholar
  72. 72.
    Hara J, Yanagisawa M, Sakurai T (2005b). Difference in obesity phenotype between orexin-knockout mice and orexin neuron-deficient mice with same genetic background and environmental conditions. Neurosci Lett, 380(3):239–242.PubMedCrossRefGoogle Scholar
  73. 73.
    Hardie DG, Carling D, Carlson M (1998). The AMP-activated/SNFI protein kinase subfamily: metabolic sensors of the eukaryotic cell? Ann Rev Biochem, 67:821–855.PubMedCrossRefGoogle Scholar
  74. 74.
    Hart RP, Buchsbaum DG, Wade JB, Hamer RM, Kwentus JA (1987). Effect of sleep deprivation on first-year residents’ response times, memory, and mood. J Med Educ, 62(11):940–2.PubMedGoogle Scholar
  75. 75.
    Hasstedt SJ, Ramirez ME, Kuida H, Williams RR (1989). Recessive inheritance of a relative fat pattern. Am J Hum Genet, 45(6):917–25.PubMedGoogle Scholar
  76. 76.
    Hautala AJ, Leon AS, Skinner JS, Rao DC, Bouchard C, Rankinen T (2007). Peroxisome proliferator-activated receptor-delta polymorphisms are associated with physical performance and plasma lipids: the HERITAGE Family Study. Am J Physiol Heart Circ Physiol, 292(5):H2498–505.PubMedCrossRefGoogle Scholar
  77. 77.
    Hawley SA, Boudeau J, Reid JL, Mustard KJ, Udd L, Makela TP, Alessi DR, Hardie DG (2003). Complexes between the LKBI tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J Biol, 2(4):28.PubMedCrossRefGoogle Scholar
  78. 78.
    Heath AC, Kendler KS, Eaves LJ, Martin NG (1990). Evidence for genetic influences on sleep disturbance and sleep pattern in twins. Sleep, 13(4):318–35.PubMedGoogle Scholar
  79. 79.
    Hersh CP, Demeo DL, Lazarus R, Celedon JC, Raby BA, Benditt JO, Criner G, Make B, Martinez FJ, Scanlon PD and others (2006). Genetic association analysis of functional impairment in chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 173(9):977–84.PubMedCrossRefGoogle Scholar
  80. 80.
    Horne JA, Anderson NR, Wilkinson RT (1983). Effects of sleep deprivation on signal detection measures of vigilance: implications for sleep function. Sleep, 6(4):347–58.PubMedGoogle Scholar
  81. 81.
    Horvath TL, Gao XB (2005). Input organization and plasticity of hypocretin neurons: possible clues to obesity’s association with insomnia. Cell Metab, 1(4):279–286.PubMedCrossRefGoogle Scholar
  82. 82.
    Hruskovicova H, Dzurenkova D, Selingerova M, Bohus B, Timkanicova B, Kovacs L (2006). The angiotensin converting enzyme I/D polymorphism in long distance runners. J Sports Med Phys Fitness, 46(3):509–13.PubMedGoogle Scholar
  83. 83.
    Hsing AW, Chokkalingam AP (2006). Prostate Cancer Epidemiology. Front Biosci, 11: 1388–1413.PubMedCrossRefGoogle Scholar
  84. 84.
    Hursting SD, Lashinger LM, Colbert LH, Rogers CJ, Wheatley KW, Nunez NP, Mahabir S, Barrett JC, Forman MR, Perkins SN (2007). Energy balance and carcinogenesis: underlying pathways and targets for intervention. Curr Cancer Drug Targets, 7(5):484–91.PubMedCrossRefGoogle Scholar
  85. 85.
    Hursting SD, Lashinger LM, Wheatley KW, Rogers CJ, Colbert LH, Nunez NP, Perkins SN (2008). Reducing the weight of cancer: mechanistic targets for breaking the obesity-carcinogenesis link. Best Pract Res Clin Endocrinol Metab, 22(4):659–69.PubMedCrossRefGoogle Scholar
  86. 86.
    Huygens W, Thomis MA, Peeters MW, Aerssens J, Janssen R, Vlietinck RF, Beunen G (2004a). Linkage of myostatin pathway genes with knee strength in humans. Physiol Genomics, 17(3):264–70.PubMedCrossRefGoogle Scholar
  87. 87.
    Huygens W, Thomis MA, Peeters MW, Aerssens J, Janssen RG, Vlietinck RF, Beunen G (2004b). A quantitative trait locus on 13q14.2 for trunk strength. Twin Res, 7(6):603–6.PubMedGoogle Scholar
  88. 88.
    Jeffreys M, Smith GD, Martin RM, Frankel S, Gunnell D (2004). Childhood body mass index and later cancer risk: a 50-year follow-up of the Boyd Orr study. Int J Cancer, 112(2):348–351.PubMedCrossRefGoogle Scholar
  89. 89.
    Kaaks R, Lukanova A, Sommersberg B (2000a). Plasma androgens, IGF-1, body size, and prostate cancer risk: a synthetic review. Prostate Cancer ProstaticDis, 3(3):157–172.CrossRefGoogle Scholar
  90. 90.
    Kaaks R, Lundin E, Rinaldi S, Manjer J, Biessy C, Soderberg S, Lenner P, Janzon L, Riboli E, Berglund G and others (2002). Prospective study of IGF-I, IGF-binding proteins, and breast cancer risk, in northern and southern Sweden. Cancer Causes Control, 13(4): 307–316.PubMedCrossRefGoogle Scholar
  91. 91.
    Kaaks R, Toniolo P, Akhmedkhanov A, Lukanova A, Biessy C, Dechaud H, Rinaldi S, Zeleniuch-Jacquotte A, Shore RE, Riboli E (2000b). Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst 92(19):1592–1600.PubMedCrossRefGoogle Scholar
  92. 92.
    Kanagy NL, Walker BR, Nelin LD (2001). Role of endothelin in intermittent hypoxia-induced hypertension. Hypertension, 37(2 Part 2):511–5.PubMedCrossRefGoogle Scholar
  93. 93.
    Kanazawa H, Tateishi Y, Yoshikawa J (2004). Acute effects of nifedipine administration in pulmonary haemodynamics and oxygen delivery during exercise in patients with chronic obstructive pulmonary disease: implication of the angiotensin-converting enzyme gene polymorphisms. Clin Physiol Funct Imaging, 24(4):224–8.PubMedCrossRefGoogle Scholar
  94. 94.
    Kasikcioglu E, Kayserilioglu A, Ciloglu F, Akhan H, Oflaz H, Yildiz S, Peker I (2004). Angiotensin-converting enzyme gene polymorphism, left ventricular remodeling, and exercise capacity in strength-trained athletes. Heart Vessels, 19(6):287–93.PubMedCrossRefGoogle Scholar
  95. 95.
    Kaye SA, Folsom AR, Soler JT, Prinease RJ, Potter JD (1991). Associations of body mass and fat distribution with sex hormone concentrations in post menopausal women. Int J Epidemiol, 20:151–156.PubMedCrossRefGoogle Scholar
  96. 96.
    Keith SW, Redden DT, Katzmarzyk PT, Boggiano MM, Hanlon EC, Benca RM, Ruden D, Pietrobelli A, Barger JL, Fontaine KR and others (2006). Putative contributors to the secular increase in obesity: exploring the roads less traveled. Int J Obes (Lond), 30(11):1585–94.CrossRefGoogle Scholar
  97. 97.
    Key TJ, Pike MC (1988). The dose-effect relationship between “unopposed” oestrogens and endometrial mitotic rate, its central role in explaining and predicting endometrial cancer risk. Br J Cancer, 57:205–212.PubMedCrossRefGoogle Scholar
  98. 98.
    Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE (2000). The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev, 21(3):215–244.PubMedCrossRefGoogle Scholar
  99. 99.
    Kimura M, Winkelmann J (2007). Genetics of sleep and sleep disorders. Cell Mol Life Sci, 64(10):1216–26.PubMedCrossRefGoogle Scholar
  100. 100.
    Kirschner MA, Samojlik E, Drejka M, Szmal E, Schneider G, Ertel N (1990). Androgen-estrogen metabolism in women with upper body versus lower body obesity. J Clin Endocrinol Metab, 70:473–479.PubMedCrossRefGoogle Scholar
  101. 101.
    Kok SW, Overeem S, Visscher TL, Lammers GJ, Seidell JC, Pijl H, Meinders AE (2003). Hypocretin deficiency in narcoleptic humans is associated with abdominal obesity. Obes Res, 11(9):1147–1154.PubMedCrossRefGoogle Scholar
  102. 102.
    Kushida C (2007). Obstructive Sleep Apnea: Diagnosis and Treatment. Informa Health Care.Google Scholar
  103. 103.
    Laposky AD, Shelton J, Bass J, Dugovic C, Perrino N, Turek FW (2006). Altered sleep regulation in leptin-deficient mice. Am J Physiol Regul Integr Comp Physiol, 290(4):R894–R903.PubMedCrossRefGoogle Scholar
  104. 104.
    Lawlor DA, Smith GD, Ebrahim S (2004). Hyperinsulinaemia and increased risk of breast cancer: findings from the British Women’s Heart and Health Study. Cancer Causes Control, 15(3):267–275.PubMedCrossRefGoogle Scholar
  105. 105.
    Lee M, Korner J (2008). Review of physiology, clinical manifestations, and management of hypothalamic obesity in humans. Pituitary, 12(2):87–95.Google Scholar
  106. 106.
    Leproult R, Copinschi G, Buxton O, Van CE (1997). Sleep loss results in an elevation of cortisol levels the next evening. Sleep, 20(10):865–870.PubMedGoogle Scholar
  107. 107.
    Ley RE, Turnbaugh PJ, Klein S, Gordon JI (2006). Microbial ecology: human gut microbes associated with obesity. Nature, 444(7122):1022–3.PubMedCrossRefGoogle Scholar
  108. 108.
    Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R and others (1997). PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science, 275(5308):1943–1947.PubMedCrossRefGoogle Scholar
  109. 109.
    Li TY, Rana JS, Manson JE, Willett WC, Stampfer MJ, Colditz GA, Rexrode KM, Hu FB (2006). Obesity as compared with physical activity in predicting risk of coronary heart disease in women. Circulation, 113(4):499–506.PubMedCrossRefGoogle Scholar
  110. 110.
    Liggett SB, Wagoner LE, Craft LL, Hornung RW, Hoit BD, McIntosh TC, Walsh RA (1998). The Ile164 beta2-adrenergic receptor polymorphism adversely affects the outcome of congestive heart failure. J Clin Invest, 102(8):1534–9.PubMedCrossRefGoogle Scholar
  111. 111.
    Lightfoot JT, Turner MJ, Knab AK, Jedlicka AE, Oshimura T, Marzec J, Gladwell W, Leamy LJ, Kleeberger SR (2007). Quantitative trait loci associated with maximal exercise endurance in mice. J Appl Physiol, 103(1):105–10.PubMedCrossRefGoogle Scholar
  112. 112.
    Lindblad M, Rodriguez LA, Lagergren J (2005). Body mass, tobacco and alcohol and risk of esophageal, gastric cardia, and gastric non-cardia adenocarcinoma among men and women in a nested case-control study. Cancer Causes Control, 16(3):285–294.PubMedCrossRefGoogle Scholar
  113. 113.
    Long JR, Liu PY, Liu YJ, Lu Y, Xiong DH, Elze L, Recker RR, Deng HW (2003). APOE and TGF-beta1 genes are associated with obesity phenotypes. J Med Genet, 40(12):918–24.PubMedCrossRefGoogle Scholar
  114. 114.
    Longo VD, Finch CE (2003). Evolutionary Medicine: From Dwarf Model Systems to Healthy Centenarians? Science, 299:1342–1346.PubMedCrossRefGoogle Scholar
  115. 115.
    Lonnqvist F, Wennlund A, Arner P (1997). Relationship between circulating leptin and peripheral fat distribution in obese subjects. Int J Obesity, 21:255–260.CrossRefGoogle Scholar
  116. 116.
    Loos RJ, Lindgren CM, Li S, Wheeler E, Zhao JH, Prokopenko I, Inouye M, Freathy RM, Attwood AP, Beckmann JS and others (2008). Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet, 40(6):768–75.PubMedCrossRefGoogle Scholar
  117. 117.
    Lopez-Alarcon M, Hunter GR, Gower BA, Fernandez JR (2007). IGF-I polymorphism is associated with lean mass, exercise economy, and exercise performance among premenopausal women. Arch Med Res, 38(1):56–63.PubMedCrossRefGoogle Scholar
  118. 118.
    Lowell BB, Spiegelman BM (2000). Towards a molecular understanding of adaptive thermogenesis. Nature, 404(6778):652–60.PubMedGoogle Scholar
  119. 119.
    Lubin F, Chetrit A, Freedman LS, Alfandary E, Fishler Y, Nitzan H, Zultan A, Modan B (2003). Body mass index at age 18 years and during adult life and ovarian cancer risk. Am J Epidemiol, 157(2):113–120.PubMedCrossRefGoogle Scholar
  120. 120.
    Lucia A, Gomez-Gallego F, Barroso I, Rabadan M, Bandres F, San Juan AF, Chicharro JL, Ekelund U, Brage S, Earnest CP and others (2005). PPARGC1A genotype (Gly482Ser) predicts exceptional endurance capacity in European men. J Appl Physiol, 99(1):344–8.PubMedCrossRefGoogle Scholar
  121. 121.
    Lukanova A, Lundin E, Micheli A, Arslan A, Ferrari P, Rinaldi S, Krogh V, Lenner P, Shore RE, Biessy C and others (2004a). Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women. Int J Cancer, 108(3):425–432.PubMedCrossRefGoogle Scholar
  122. 122.
    Lukanova A, Zeleniuch-Jacquotte A, Lundin E, Micheli A, Arslan AA, Rinaldi S, Muti P, Lenner P, Koenig KL, Biessy C and others (2004b). Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer. Int J Cancer, 108(2):262–268.CrossRefGoogle Scholar
  123. 123.
    Ma J, Pollak M, Giovannucci E, Chan JM, Tao Y, Hennekens C, Stampfer MJ (2000). A prospective study of plasma levels of insulin-like growth factor I (IGF-I) and IGF-binding protein-3, and colorectal cancer risk among men. Growth Horm IGF Res, 10 Suppl A:S28–S29.PubMedCrossRefGoogle Scholar
  124. 124.
    MacArthur DG, Seto JT, Raftery JM, Quinlan KG, Huttley GA, Hook JW, Lemckert FA, Kee AJ, Edwards MR, Berman Y and others (2007). Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans. Nat Genet, 39(10):1261–5.PubMedCrossRefGoogle Scholar
  125. 125.
    Marik PE (2000). Leptin, obesity, and obstructive sleep apnea. Chest, 118(3):569–71.PubMedCrossRefGoogle Scholar
  126. 126.
    McCole SD, Shuldiner AR, Brown MD, Moore GE, Ferrell RE, Wilund KR, Huberty A, Douglass LW, Hagberg JM (2004). Beta2- and beta3-adrenergic receptor polymorphisms and exercise hemodynamics in postmenopausal women. J Appl Physiol, 96(2):526–30.PubMedCrossRefGoogle Scholar
  127. 127.
    Medlund P, Cederlof R, Floderus-Myrhed B, Friberg L, Sorensen S (1976). A new Swedish twin registry containing environmental and medical base line data from about 14,000 same-sexed pairs born 1926–58. Acta Med Scand Suppl, 600:1–111.PubMedGoogle Scholar
  128. 128.
    Meyre D, Delplanque J, Chevre JC, Lecoeur C, Lobbens S, Gallina S, Durand E, Vatin V, Degraeve F, Proenca C and others (2009). Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nat Genet, 41(2):157–9.PubMedCrossRefGoogle Scholar
  129. 129.
    Modell S, Ising M, Holsboer F, Lauer CJ (2002). The Munich Vulnerability Study on Affective Disorders: stability of polysomnographic findings over time. Biol Psychiatry, 52(5):430–7.PubMedCrossRefGoogle Scholar
  130. 130.
    Moll PP, Burns TL, Lauer RM (1991). The genetic and environmental sources of body mass index variability: the Muscatine Ponderosity Family Study. Am J Hum Genet, 49(6):1243–55.PubMedGoogle Scholar
  131. 131.
    Montague CT, Prins JB, Sanders L et al. (1997). Depot- and sex-specific differences in human leptin mRNA expression: implications for the control of regional fat distribution. Diabetes, 46:342–347.PubMedCrossRefGoogle Scholar
  132. 132.
    Montgomery HE, Marshall R, Hemingway H, Myerson S, Clarkson P, Dollery C, Hayward M, Holliman DE, Jubb M, World M and others (1998). Human gene for physical performance. Nature, 393(6682):221–2.PubMedCrossRefGoogle Scholar
  133. 133.
    Moore GE, Shuldiner AR, Zmuda JM, Ferrell RE, McCole SD, Hagberg JM (2001). Obesity gene variant and elite endurance performance. Metabolism, 50(12):1391–2.PubMedCrossRefGoogle Scholar
  134. 134.
    Moore JW, Key TJ, Bulbrook RD, Clark GM, Allen DS, Wang DY, Pike MC (1987). Sex hormone binding globulin and risk factors for breast cancer in a population of normal women who had never used exogenous sex hormones. Br J Cancer, 56:661–666.PubMedCrossRefGoogle Scholar
  135. 135.
    Moran CN, Yang N, Bailey ME, Tsiokanos A, Jamurtas A, MacArthur DG, North K, Pitsiladis YP, Wilson RH (2007). Association analysis of the ACTN3 R577X polymorphism and complex quantitative body composition and performance phenotypes in adolescent Greeks. Eur J Hum Genet, 15(1):88–93.PubMedCrossRefGoogle Scholar
  136. 136.
    Must A, Jacques PF, Dallal GE, Bajema CJ, Dietz WH (1992). Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935. N Engl J Med, 327(19):1350–5.PubMedCrossRefGoogle Scholar
  137. 137.
    Myerson S, Hemingway H, Budget R, Martin J, Humphries S, Montgomery H (1999). Human angiotensin I-converting enzyme gene and endurance performance. J Appl Physiol, 87(4):1313–6.PubMedGoogle Scholar
  138. 138.
    National Sleep Foundation (2000). Omnibus Sleep in America Poll. National Sleep Foundation, Washington, DC.Google Scholar
  139. 139.
    Nazarov IB, Woods DR, Montgomery HE, Shneider OV, Kazakov VI, Tomilin NV, Rogozkin VA (2001). The angiotensin converting enzyme I/D polymorphism in Russian athletes. Eur J Hum Genet, 9(10):797–801.PubMedCrossRefGoogle Scholar
  140. 140.
    Nishino S, Mignot E (1997). Pharmacological aspects of human and canine narcolepsy. Prog Neurobiol, 52(1):27–78.PubMedCrossRefGoogle Scholar
  141. 141.
    Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E (2000). Hypocretin (orexin) deficiency in human narcolepsy. Lancet, 355(9197):39–40.PubMedCrossRefGoogle Scholar
  142. 142.
    Norman RA, Thompson DB, Foroud T, Garvey WT, Bennett PH, Bogardus C, Ravussin E (1997). Genomewide search for genes influencing percent body fat in Pima Indians: suggestive linkage at chromosome 11q21-q22. Pima Diabetes Gene Group. Am J Hum Genet, 60(1):166–173.PubMedGoogle Scholar
  143. 143.
    Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM (2006). Prevalence of overweight and obesity in the United States, 1999–2004. JAMA, 295(13):1549–55.PubMedCrossRefGoogle Scholar
  144. 144.
    Oh SD (2007). The distribution of I/D polymorphism in the ACE gene among Korean male elite athletes. J Sports Med Phys Fitness, 47(2):250–4.PubMedGoogle Scholar
  145. 145.
    Ondo WG, Vuong KD, Wang Q (2000). Restless legs syndrome in monozygotic twins: clinical correlates. Neurology, 55(9):1404–6.PubMedCrossRefGoogle Scholar
  146. 146.
    Paganini-Hill A, Martin AO, Spence MA (1981). The S-leut anthropometric traits: genetic analysis. Am J Phys Anthropol, 55(1):55–67.PubMedCrossRefGoogle Scholar
  147. 147.
    Palmqvist R, Hallmans G, Rinaldi S, Biessy C, Stenling R, Riboli E, Kaaks R (2002). Plasma insulin-like growth factor 1, insulin-like growth factor binding protein 3, and risk of colorectal cancer: a prospective study in northern Sweden. Gut, 50(5):642–646.PubMedCrossRefGoogle Scholar
  148. 148.
    Parkin DM, Bray F, Ferlay J, Pisani P (2005). Global cancer statistics, 2002. CA Cancer J Clin, 55:74–108.PubMedCrossRefGoogle Scholar
  149. 149.
    Patel SR, Palmer LJ, Larkin EK, Jenny NS, White DP, Redline S (2004). Relationship between obstructive sleep apnea and diurnal leptin rhythms. Sleep, 27(2):235–9.PubMedGoogle Scholar
  150. 150.
    Peppard PE, Young T, Palta M, Skatrud J (2000). Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med, 342(19):1378–1384.PubMedCrossRefGoogle Scholar
  151. 151.
    Pepperell JC, Ramdassingh-Dow S, Crosthwaite N, Mullins R, Jenkinson C, Stradling JR, Davies RJ (2002). Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial. Lancet, 359(9302):204–10.PubMedCrossRefGoogle Scholar
  152. 152.
    Peyrat JP, Bonneterre J, Hecquet B, Vennin P, Louchez MM, Fournier C, Lefebvre J, Demaille A (1993). Plasma insuin-like growth factor-I (IGF-I) concentrations in human breast cancer. Eur J Cancer, 29A:492–497.PubMedCrossRefGoogle Scholar
  153. 153.
    Pirolli A, Smith C (1989). REM sleep deprivation in humans impairs learning a complex task. Sleep Research, 18:375.Google Scholar
  154. 154.
    Playford MP, Bicknell D, Bodmer WF, Macaulay VM (2000). Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin. Proc Natl Acad Sci USA, 97(22):12103–12108.PubMedCrossRefGoogle Scholar
  155. 155.
    Polednak AP (2003). Trends in incidence rates for obesity-associated cancers in the US. Cancer Detect Prev, 27(6):415–21.PubMedCrossRefGoogle Scholar
  156. 156.
    Potischman N, Hoover RN, Brinton LA, et al. (1996). Case-control study of endogenous steroid hormones and endometrial cancer. J Natl Cancer Inst, 88:1127–1135.PubMedCrossRefGoogle Scholar
  157. 157.
    Potischman N, Troisi R (1999). In-utero and early life exposures in relation to risk of breast cancer. Cancer Causes Control, 10(6):561–573.PubMedCrossRefGoogle Scholar
  158. 158.
    Rajala MW, Obici S, Scherer PE, Rossetti L (2003). Adipose-derived resistin and gut-derived resistin-like molecule-beta selectively impair insulin action on glucose production. J Clin Invest, 111(2):225–230.PubMedGoogle Scholar
  159. 159.
    Ravussin E, Lillioja S, Knowler WC, Christin L, Freymond D, Abbott WG, Boyce V, Howard BV, Bogardus C (1988). Reduced rate of energy expenditure as a risk factor for body-weight gain. N Engl J Med, 318(8):467–72.PubMedCrossRefGoogle Scholar
  160. 160.
    Redline S, Tishler PV, Schluchter M, Aylor J, Clark K, Graham G (1999). Risk factors for sleep-disordered breathing in children. Associations with obesity, race, and respiratory problems. Am J Respir Crit Care Med, 159(5 Pt 1):1527–1532.PubMedGoogle Scholar
  161. 161.
    Reigle BS, Wonders K (2009). Breast cancer and the role of exercise in women. Methods Mol Biol, 472:169–89.PubMedCrossRefGoogle Scholar
  162. 162.
    Rico-Sanz J, Rankinen T, Rice T, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C (2004). Quantitative trait loci for maximal exercise capacity phenotypes and their responses to training in the HERITAGE Family Study. Physiol Genomics, 16(2):256–60.PubMedGoogle Scholar
  163. 163.
    Roberts SB, Young VR (1988). Energy costs of fat and protein deposition in the human infant. Am J Clin Nutr, 48(4):951–5.PubMedGoogle Scholar
  164. 164.
    Rose D, Gilhooly EM, Nixon D (2002). Adverse effects of obesity on breast cancer prognosis, and biological actions of leptin. Int J Oncol, 6:1285–1292.Google Scholar
  165. 165.
    Rubio JC, Martin MA, Rabadan M, Gomez-Gallego F, San Juan AF, Alonso JM, Chicharro JL, Perez M, Arenas J, Lucia A (2005). Frequency of the C34T mutation of the AMPD1 gene in world-class endurance athletes: does this mutation impair performance? J Appl Physiol, 98(6):2108–12.PubMedCrossRefGoogle Scholar
  166. 166.
    Salgado R, Junius S, Benoy I, Van DP, Vermeulen P, Van ME, Huget P, Dirix LY (2003). Circulating interleukin-6 predicts survival in patients with metastatic breast cancer. Int J Cancer, 103(5):642–646.PubMedCrossRefGoogle Scholar
  167. 167.
    Samanic C, Chow WH, Gridley G, Jarvholm B, Fraumeni JF Jr. (2006). Relation of body mass index to cancer risk in 362, 552 Swedish men. Cancer Causes Control, 17(7):901–909.PubMedCrossRefGoogle Scholar
  168. 168.
    Sandilands AJ, Parameshwar J, Large S, Brown MJ, O’Shaughnessy KM (2005). Confirmation of a role for the 389R>G beta-1 adrenoceptor polymorphism on exercise capacity in heart failure. Heart, 91(12):1613–4.PubMedCrossRefGoogle Scholar
  169. 169.
    Saunders CJ, Xenophontos SL, Cariolou MA, Anastassiades LC, Noakes TD, Collins M (2006). The bradykinin beta 2 receptor (BDKRB2) and endothelial nitric oxide synthase 3 (NOS3) genes and endurance performance during Ironman Triathlons. Hum Mol Genet, 15(6):979–87.PubMedCrossRefGoogle Scholar
  170. 170.
    Scanavini D, Bernardi F, Castoldi E, Conconi F, Mazzoni G (2002). Increased frequency of the homozygous II ACE genotype in Italian Olympic endurance athletes. Eur J Hum Genet, 10(10):576–7.PubMedCrossRefGoogle Scholar
  171. 171.
    Schmelzle T, Hall MN (2000). TOR, a central controller of cell growth. Cell, 103(2):253–62.PubMedCrossRefGoogle Scholar
  172. 172.
    Schoen RE, Tangen CM, Kuller LH, Burke GL, Cushman M, Tracy RP, Dobs A, Savage PJ (1999). Increased blood glucose and insulin, body size, and incident colorectal cancer. J Natl Cancer Inst, 91(13):1147–1154.PubMedCrossRefGoogle Scholar
  173. 173.
    Schwartz MW, Porte D Jr. (2005). Diabetes, obesity, and the brain. Science, 307(5708):375–379.PubMedCrossRefGoogle Scholar
  174. 174.
    Setiawan VW, Doherty JA, Shu X, Akbari MR, Chen C, et al. (2009). Two Estrogen-Reated Variants in CYP19A1 and Endometrial Cancer Risk: A Pooled Analysis in the Epidemiology of Endometrail Cancer Consortium. Cancer Epidemiol Biomarkers Prev, 18(1):242–247.PubMedCrossRefGoogle Scholar
  175. 175.
    Sharifi N, Gulley J, Dahut WL (2005). Androgen deprivation therapy for prostate cancer. JAMA, 294:238–244.PubMedCrossRefGoogle Scholar
  176. 176.
    Shirai H, Oishi K, Kudo T, Shibata S, Ishida N (2007). PPARalpha is a potential therapeutic target of drugs to treat circadian rhythm sleep disorders. Biochem Biophys Res Commun, 357(3):679–82.PubMedCrossRefGoogle Scholar
  177. 177.
    Silberberg R (1972). Articular aging and osteoarthrosis in dwarf mice. Pathol Microbiol, 38(6):417–430.Google Scholar
  178. 178.
    Smith C, Pirolli A (1989). Learning deficits following REM sleep deprivation of either the first two or last two REM periods of the night. Sleep Research, 18:377.Google Scholar
  179. 179.
    Smith JE, Tolson JM (2008). Recognition, diagnosis, and treatment of restless legs syndrome. J Am Acad Nurse Pract, 20(8):396–401.PubMedCrossRefGoogle Scholar
  180. 180.
    Sookoian S, Gemma C, Gianotti TF, Burgueno A, Castano G, Pirola CJ (2008). Genetic variants of Clock transcription factor are associated with individual susceptibility to obesity. Am J Clin Nutr, 87(6):1606–15.PubMedGoogle Scholar
  181. 181.
    Spiegel K, Leproult R, Colecchia EF, L’Hermite-Baleriaux M, Nie Z, Copinschi G, Van CE (2000). Adaptation of the 24-h growth hormone profile to a state of sleep debt. Am J Physiol Regul Integr Comp Physiol, 279(3):R874–R883.PubMedGoogle Scholar
  182. 182.
    Spilsbury JC, Storfer-Isser A, Drotar D, Rosen CL, Kirchner LH, Benham H, Redline S (2004). Sleep behavior in an urban US sample of school-aged children. Arch Pediatr Adolesc Med, 158(10):988–94.PubMedCrossRefGoogle Scholar
  183. 183.
    Stattin P, Lukanova A, Biessy C, Soderberg S, Palmqvist R, Kaaks R, Olsson T, Jellum E (2004). Obesity and colon cancer: does leptin provide a link? Int J Cancer, 109(1):149–152.PubMedCrossRefGoogle Scholar
  184. 184.
    Stavola BL, Hardy R, Kuh D, Silva IS, Wadsworth M, Swerdlow AJ (2000). Birthweight, childhood growth and risk of breast cancer in a British cohort. Br J Cancer, 83(7):964–968.PubMedCrossRefGoogle Scholar
  185. 185.
    Stunkard AJ, Foch TT, Hrubec Z (1986). A twin study of human obesity. Jama, 256(1):51–4.PubMedCrossRefGoogle Scholar
  186. 186.
    Tafti M, Maret S, Dauvilliers Y (2005). Genes for normal sleep and sleep disorders. Ann Med, 37(8):580–9.PubMedCrossRefGoogle Scholar
  187. 187.
    Taheri S, Mignot E (2002). The genetics of sleep disorders. Lancet Neurol, 1(4):242–50.PubMedCrossRefGoogle Scholar
  188. 188.
    Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, Richards GJ, Campfield LA, Clark FT, Deeds J, Muir C, et al. (1995). Identification and expression cloning of a leptin receptor, OB-R. Cell, 83:1263–1271.PubMedCrossRefGoogle Scholar
  189. 189.
    Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A, Styrkarsdottir U, Gretarsdottir S, Thorlacius S, Jonsdottir I and others (2009). Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet, 41(1):18–24.PubMedCrossRefGoogle Scholar
  190. 190.
    Toi M, Inada K, Suzuki H, Tominaga T (1995). Tumor angiogenesis in breast cancer: its importance as a prognostic indicator and the association with vascular endothelial growth factor expression. Breast Cancer Res Treat, 36(2):193–204.PubMedCrossRefGoogle Scholar
  191. 191.
    Toniolo P, Bruning PF, Akhmedkhanov A, Bonfrer JM, Koenig KL, Lukanova A, Shore RE, Zeleniuch-Jacquotte A (2000). Serum insulin-like growth factor-I and breast cancer. Int J Cancer, 88(5):828–832.PubMedCrossRefGoogle Scholar
  192. 192.
    Trayhurn P, Bing C, Wood IS (2006). Adipose tissue and adipokines–energy regulation from the human perspective. J Nutr, 136(7 Suppl):1935S–1939S.PubMedGoogle Scholar
  193. 193.
    Treuth MS, Baggett CD, Pratt CA, Going SB, Elder JP, Charneco EY, Webber LS (2009). A Longitudinal Study of Sedentary Behavior and Overweight in Adolescent Girls. Obesity (Silver Spring). 17(5):1003–8.Google Scholar
  194. 194.
    Turek FW, Joshu C, Kohsaka A, Lin E, Ivanova G, McDearmon E, Laposky A, Losee-Olson S, Easton A, Jensen DR and others (2005). Obesity and metabolic syndrome in circadian Clock mutant mice. Science, 308(5724):1043–5.PubMedCrossRefGoogle Scholar
  195. 195.
    Turgut G, Kaptanoglu B, Turgut S, Enli Y, Genc O (2004). Effects of chronic aluminum administration on blood and liver iron-related parameters in mice. Yonsei Med J, 45(1):135–9.PubMedGoogle Scholar
  196. 196.
    Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI (2006). An obesity-associated gut microbiome with increased capacity for energy harvest. Nature, 444(7122):1027–31.PubMedCrossRefGoogle Scholar
  197. 197.
    Van Cauter E, Copinschi G (2000). Interrelationships between growth hormone and sleep. Growth Horm IGF Res, 10 Suppl B:S57–62.PubMedCrossRefGoogle Scholar
  198. 198.
    Van CE, Plat L, Copinschi G (1998). Interrelations between sleep and the somatotropic axis. Sleep, 21(6):553–566.Google Scholar
  199. 199.
    van Ginneken V, Sitnyakowsky L, Jeffery JE (2009). Infectobesity: viral infections (especially with human adenovirus-36: Ad-36) may be a cause of obesity. Med Hypotheses, 72(4):383–8.PubMedCrossRefGoogle Scholar
  200. 200.
    van Rossum EF, Voorhoeve PG, te Velde SJ, Koper JW, Delemarre-van de Waal HA, Kemper HC, Lamberts SW (2004). The ER22/23EK polymorphism in the glucocorticoid receptor gene is associated with a beneficial body composition and muscle strength in young adults. J Clin Endocrinol Metab, 89(8):4004–9.PubMedCrossRefGoogle Scholar
  201. 201.
    Vincent B, De Bock K, Ramaekers M, Van den Eede E, Van Leemputte M, Hespel P, Thomis MA (2007). ACTN3 (R577X) genotype is associated with fiber type distribution. Physiol Genomics, 32(1):58–63.PubMedCrossRefGoogle Scholar
  202. 202.
    Vioque J, Torres A, Quiles J (2000). Time spent watching television, sleep duration and obesity in adults living in Valencia, Spain. Int J Obes Relat Metab Disord, 24(12):1683–8.PubMedCrossRefGoogle Scholar
  203. 203.
    Wagoner LE, Craft LL, Singh B, Suresh DP, Zengel PW, McGuire N, Abraham WT, Chenier TC, Dorn GW, 2nd, Liggett SB (2000). Polymorphisms of the beta(2)-adrenergic receptor determine exercise capacity in patients with heart failure. Circ Res, 86(8):834–40.PubMedCrossRefGoogle Scholar
  204. 204.
    Wagoner LE, Craft LL, Zengel P, McGuire N, Rathz DA, Dorn GW, 2nd, Liggett SB (2002). Polymorphisms of the beta1-adrenergic receptor predict exercise capacity in heart failure. Am Heart J, 144(5):840–6.PubMedGoogle Scholar
  205. 205.
    Wang W, Guan KL (2009). AMPK and Cancer. Acta Physiol.Google Scholar
  206. 206.
    Ways JA, Cicila GT, Garrett MR, Koch LG (2002). A genome scan for Loci associated with aerobic running capacity in rats. Genomics, 80(1):13–20.PubMedCrossRefGoogle Scholar
  207. 207.
    Webb WB, Campbell SS (1983). Relationships in sleep characteristics of identical and fraternal twins. Arch Gen Psychiatry, 40(10):1093–5.PubMedCrossRefGoogle Scholar
  208. 208.
    Whitaker RC, Wright JA, Pepe MS, Seidel KD, Dietz WH (1997a). Predicting obesity in young adulthood from childhood and parental obesity. N Engl J Med, 337(13):869–73.PubMedCrossRefGoogle Scholar
  209. 209.
    Whitaker RC, Wright JA, Pepe MS, Seidel KD, Dietz WH (1997b). Predicting obesity in young adulthood from childhood and parental obesity. N Engl J Med, 337(13):869–873.PubMedCrossRefGoogle Scholar
  210. 210.
    Willer CJ, Speliotes EK, Loos RJF, Li S, Lindgren CM, Heid IM, et al. (2009). Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat. Genetics, 41(1):25–34.PubMedGoogle Scholar
  211. 211.
    Wingard DL, Berkman LF (1983). Mortality risk associated with sleeping patterns among adults. Sleep, 6(2):102–107.PubMedGoogle Scholar
  212. 212.
    Winkelmann J, Wetter TC, Collado-Seidel V, Gasser T, Dichgans M, Yassouridis A, Trenkwalder C (2000). Clinical characteristics and frequency of the hereditary restless legs syndrome in a population of 300 patients. Sleep, 23(5):597–602.PubMedGoogle Scholar
  213. 213.
    Wolf AM, Hunter DJ, Colditz GA, Manson JE, Stampfer MJ, Corsano KA, Rosner B, Kriska A, Willett WC (1994). Reproducibility and validity of a self-administered physical activity questionnaire. Int J Epidemiol, 23(5):991–9.PubMedCrossRefGoogle Scholar
  214. 214.
    Wolfarth B, Rankinen T, Muhlbauer S, Scherr J, Boulay MR, Perusse L, Rauramaa R, Bouchard C (2007). Association between a beta2-adrenergic receptor polymorphism and elite endurance performance. Metabolism, 56(12):1649–51.PubMedCrossRefGoogle Scholar
  215. 215.
    Wolfarth B, Rivera MA, Oppert JM, Boulay MR, Dionne FT, Chagnon M, Gagnon J, Chagnon Y, Perusse L, Keul J and others (2000). A polymorphism in the alpha2a-adrenoceptor gene and endurance athlete status. Med Sci Sports Exerc, 32(10):1709–12.PubMedCrossRefGoogle Scholar
  216. 216.
    Wong SL, Leatherdale ST (2009). Association between sedentary behavior, physical activity, and obesity: inactivity among active kids. Prev Chronic Dis, 6(1):A26.PubMedGoogle Scholar
  217. 217.
    Woods A, Johnstone SR, Dickerson K, Leiper FC, Fryer LG, Neumann D, Schlattner U, Wallimann T, Carlson M, Carling D (2003). LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr Biol, 13(22):2004–2008.PubMedCrossRefGoogle Scholar
  218. 218.
    Woods D, Hickman M, Jamshidi Y, Brull D, Vassiliou V, Jones A, Humphries S, Montgomery H (2001). Elite swimmers and the D allele of the ACE I/D polymorphism. Hum Genet, 108(3):230–2.PubMedCrossRefGoogle Scholar
  219. 219.
    Woods SC, Seeley RJ, Porte D, Jr. et al. (1998). Signals that regulate food intake and energy homeostasis. Science, 280:1378–1383.PubMedCrossRefGoogle Scholar
  220. 220.
    World Health Organization (2006). World Health Organization Database.Google Scholar
  221. 221.
    Yang N, MacArthur DG, Wolde B, Onywera VO, Boit MK, Lau SY, Wilson RH, Scott RA, Pitsiladis YP, North K (2007). The ACTN3 R577X polymorphism in East and West African athletes. Med Sci Sports Exerc, 39(11):1985–8.PubMedCrossRefGoogle Scholar
  222. 222.
    Zeleniuch-Jacquotte A, Akhmedkhanov A, Kato I, et al. (2001). Postmenopausal endogenous oestrogens and risk of endometrial cancer: results of a prospective study. Br J Cancer, 84:975–981.PubMedCrossRefGoogle Scholar
  223. 223.
    Zhang Y L (1998). Molecular physiology of leptin and its receptor. N Engl J Med, 14:17–35.Google Scholar
  224. 224.
    Zhao B, Moochhala SM, Tham S, Lu J, Chia M, Byrne C, Hu Q, Lee LK (2003). Relationship between angiotensin-converting enzyme ID polymorphism and VO(2max) of Chinese males. Life Sci, 73(20):2625–30.PubMedCrossRefGoogle Scholar
  225. 225.
    Zonta LA, Jayakar SD, Bosisio M, Galante A, Pennetti V (1987). Genetic analysis of human obesity in an Italian sample. Hum Hered, 37(3):129–39.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Courtney Gray-McGuire
    • 1
  • Indra Adrianto
    • 2
  • Thuan Nguyen
    • 2
  • Chee Paul Lin
    • 2
  1. 1.Arthritis and Immunology Research ProgramOklahoma Medical Research FoundationOklahoma CityUSA
  2. 2.Arthritis and Immunology Research ProgramOklahoma Medical Research FoundationOklahoma CityUSA

Personalised recommendations