Reviews in Endocrine and Metabolic Disorders

, Volume 17, Issue 3, pp 389–403 | Cite as

Obesity as a risk factor for malignant melanoma and non-melanoma skin cancer

  • K. Karimi
  • T. H. Lindgren
  • C. A. Koch
  • Robert T. Brodell


The dramatic increases in incidence of both obesity and many cancers including skin cancer emphasize the need to better understand the pathophysiology of both conditions and their connections. Melanoma is considered the fastest growing cancer and rates of non-melanoma skin cancer have also increased over the last decade. The molecular mechanisms underlying the association between obesity and skin cancer are not clearly understood but emerging evidence points to changes in the tumor microenvironment including aberrant cell signaling and genomic instability in the chronic inflammatory state many obese individuals experience. This article reviews the literature linking obesity to melanoma and non-melanoma skin cancer.


Melanoma Obesity Non-melanoma skin cancer Basal cell carcinoma Squamous cell carcinoma Inflammation Leptin Insulin 


Compliance with ethical standards

Conflict of interest

The authors Karen Karimi, Robert Brodell, Taylor Lindgren, and Christian A. Koch declare that there is no relevant conflict related to this work.


  1. 1.
    Wolin KY, Carson K, Colditz GA. Obesity and cancer. Oncologist. 2010;15(6):556–65. doi: 10.1634/theoncologist.2009-0285.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Gallagher E, LeRoith D. Obesity and diabetes: the increased risk of cancer and cancer-related mortality. Physiol Rev. 2015;95(3):727–48.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Albanes D, Winick M. Are cell number and cell proliferation risk factors for cancer? J Natl Cancer Inst. 1988;80(10):772–4.PubMedCrossRefGoogle Scholar
  4. 4.
    Scrimshaw NS, SanGiovanni JP. Synergism of nutrition, infection, and immunity: an overview. Am J Clin Nutr. 1997;66(2):464S–77S.PubMedGoogle Scholar
  5. 5.
    Koch CA, Diamanti-Kandarakis E. Introduction to endocrine disrupting chemicals—is it time to act? Rev Endocr Metab Disord. 2015;16(4):269–70.PubMedCrossRefGoogle Scholar
  6. 6.
    Kirkpatrick CS, White E, Lee JA. Case–control study of malignant melanoma in Washington State. II. Diet, alcohol, and obesity. Am J Epidemiol. 1994;139(9):869–80.PubMedGoogle Scholar
  7. 7.
    Samanic C, Chow WH, Gridley G, Jarvholm B, Fraumeni Jr JF. Relation of body mass index to cancer risk in 362,552 Swedish men. Cancer Causes Control. 2006;17(7):901–9. doi: 10.1007/s10552-006-0023-9.PubMedCrossRefGoogle Scholar
  8. 8.
    Samanic C, Gridley G, Chow WH, Lubin J, Hoover RN, Fraumeni Jr JF. Obesity and cancer risk among White and Black United States veterans. Cancer Causes Control. 2004;15(1):35–43. doi: 10.1023/ Scholar
  9. 9.
    Dubin N, Moseson M, Pasternack BS. Epidemiology of malignant melanoma: pigmentary traits, ultraviolet radiation, and the identification of high-risk populations. Recent Results Cancer Res. 1986;102:56–75.PubMedCrossRefGoogle Scholar
  10. 10.
    Gallus S, Naldi L, Martin L, Martinelli M, La Vecchia C. Oncology Study Group of the Italian Group for Epidemiologic Research in D. Anthropometric measures and risk of cutaneous malignant melanoma: a case–control study from Italy. Melanoma Res. 2006;16(1):83–7. doi: 10.1097/01.cmr.0000194429.77643.76.PubMedCrossRefGoogle Scholar
  11. 11.
    Dennis LK, Lowe JB, Lynch CF, Alavanja MC. Cutaneous melanoma and obesity in the Agricultural Health Study. Ann Epidemiol. 2008;18(3):214–21. doi: 10.1016/j.annepidem.2007.09.003.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Tang JY, Henderson MT, Hernandez-Boussard T, Kubo J, Desai M, Sims ST, et al. Lower skin cancer risk in women with higher body mass index: the women’s health initiative observational study. Cancer Epidemiol Biomarkers Prev. 2013;22(12):2412–5. doi: 10.1158/1055-9965.EPI-13-0647.PubMedCrossRefGoogle Scholar
  13. 13.
    Pothiawala S, Qureshi AA, Li Y, Han J. Obesity and the incidence of skin cancer in US Caucasians. Cancer Causes Control : CCC. 2012;23(5):717–26. doi: 10.1007/s10552-012-9941-x.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Sergentanis TN, Antoniadis AG, Gogas HJ, Antonopoulos CN, Adami HO, Ekbom A, et al. Obesity and risk of malignant melanoma: a meta-analysis of cohort and case–control studies. Eur J Cancer. 2013;49(3):642–57. doi: 10.1016/j.ejca.2012.08.028.PubMedCrossRefGoogle Scholar
  15. 15.
    Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371(9612):569–78. doi: 10.1016/S0140-6736(08)60269-X.PubMedCrossRefGoogle Scholar
  16. 16.
    Dobbins M, Decorby K, Choi BC. The association between obesity and cancer risk: a meta-analysis of observational studies from 1985 to 2011. ISRN Prev Med. 2013;2013:680536. doi: 10.5402/2013/680536.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Veierod MB, Thelle DS, Laake P. Diet and risk of cutaneous malignant melanoma: a prospective study of 50,757 Norwegian men and women. Int J Cancer. 1997;71(4):600–4.PubMedCrossRefGoogle Scholar
  18. 18.
    Olsen CM, Green AC, Zens MS, Stukel TA, Bataille V, Berwick M, et al. Anthropometric factors and risk of melanoma in women: a pooled analysis. Int J Cancer. 2008;122(5):1100–8. doi: 10.1002/ijc.23214.PubMedCrossRefGoogle Scholar
  19. 19.
    Praestegaard C, Kjaer SK, Christensen J, Tjonneland A, Halkjaer J, Jensen A. Obesity and risks for malignant melanoma and non-melanoma skin cancer: results from a large Danish prospective cohort study. J Invest Dermatol. 2015;135(3):901–4. doi: 10.1038/jid.2014.438.PubMedCrossRefGoogle Scholar
  20. 20.
    Fruhbeck G. Intracellular signalling pathways activated by leptin. Biochem J. 2006;393(Pt 1):7–20. doi: 10.1042/BJ20051578.PubMedCrossRefGoogle Scholar
  21. 21.
    Courneya KS, Katzmarzyk PT, Bacon E. Physical activity and obesity in Canadian cancer survivors: population-based estimates from the 2005 Canadian Community Health Survey. Cancer. 2008;112(11):2475–82. doi: 10.1002/cncr.23455.PubMedCrossRefGoogle Scholar
  22. 22.
    Sahl WJ, Glore S, Garrison P, Oakleaf K, Johnson SD. Basal cell carcinoma and lifestyle characteristics. Int J Dermatol. 1995;34(6):398–402.PubMedCrossRefGoogle Scholar
  23. 23.
    Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults, 1999–2000. JAMA. 2002;288(14):1723–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Brandon EL, Gu JW, Cantwell L, He Z, Wallace G, Hall JE. Obesity promotes melanoma tumor growth: role of leptin. Cancer Biol Ther. 2009;8(19):1871–9.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Monteiro CA, Moura EC, Conde WL, Popkin BM. Socioeconomic status and obesity in adult populations of developing countries: a review. Bull World Health Organ. 2004;82(12):940–6.PubMedGoogle Scholar
  26. 26.
    Popkin BM, Gordon-Larsen P. The nutrition transition: worldwide obesity dynamics and their determinants. Int J Obes Relat Metab Disord. 2004;28 Suppl 3:S2–9. doi: 10.1038/sj.ijo.0802804.PubMedCrossRefGoogle Scholar
  27. 27.
    Li X, Liang L, Zhang M, Song F, Nan H, Wang LE, et al. Obesity-related genetic variants, human pigmentation, and risk of melanoma. Hum Genet. 2013;132(7):793–801. doi: 10.1007/s00439-013-1293-4.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Frisancho AR, Wainwright R, Way A. Heritability and components of phenotypic expression in skin reflectance of Mestizos from the Peruvian lowlands. Am J Phys Anthropol. 1981;55(2):203–8. doi: 10.1002/ajpa.1330550207.PubMedCrossRefGoogle Scholar
  29. 29.
    Harrison GA, Owen JJ. Studies on the inheritance of human skin colour. Ann Hum Genet. 1964;28:27–37.PubMedCrossRefGoogle Scholar
  30. 30.
    Turner JB, Kumar A, Koch CA. The effects of indoor and outdoor temperature on metabolic rate and adipose tissue—the Mississippi perspective on the obesity epidemic. Rev Endocr Metab Disord. 2016;17(1):61–71. doi: 10.1007/s11154-016-9358-z.PubMedCrossRefGoogle Scholar
  31. 31.
    Tai N, Wong FS, Wen L. The role of gut microbiota in the development of type 1, type 2 diabetes mellitus and obesity. Rev Endocr Metab Disord. 2015;16(1):55–65. doi: 10.1007/s11154-015-9309-0.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Gerstenblith MR, Shi J, Landi MT. Genome-wide association studies of pigmentation and skin cancer: a review and meta-analysis. Pigment Cell Melanoma Res. 2010;23(5):587–606. doi: 10.1111/j.1755-148X.2010.00730.x.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Nan H, Kraft P, Hunter DJ, Han J. Genetic variants in pigmentation genes, pigmentary phenotypes, and risk of skin cancer in Caucasians. Int J Cancer. 2009;125(4):909–17. doi: 10.1002/ijc.24327.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    McAllister EJ, Dhurandhar NV, Keith SW, Aronne LJ, Barger J, Baskin M, et al. Ten putative contributors to the obesity epidemic. Crit Rev Food Sci Nutr. 2009;49(10):868–913. doi: 10.1080/10408390903372599.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Charriere G, Cousin B, Arnaud E, Andre M, Bacou F, Penicaud L, et al. Preadipocyte conversion to macrophage. Evidence of plasticity. J Biol Chem. 2003;278(11):9850–5. doi: 10.1074/jbc.M210811200.PubMedCrossRefGoogle Scholar
  36. 36.
    Wang J, Ding N, Li Y, Cheng H, Wang D, Yang Q, et al. Insulin-like growth factor binding protein 5 (IGFBP5) functions as a tumor suppressor in human melanoma cells. Oncotarget. 2015;6(24):20636–49.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Wang H, Ye J. Regulation of energy balance by inflammation: common theme in physiology and pathology. Rev Endocr Metab Disord. 2015;16(1):47–54.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Kloting N, Bluher M. Adipocyte dysfunction, inflammation and metabolic syndrome. Rev Endocr Metab Disord. 2014;15(4):277–87.PubMedCrossRefGoogle Scholar
  39. 39.
    Ngo HT, Hetland RB, Nygaard UC, Steffensen IL. Genetic and diet-induced obesity increased intestinal tumorigenesis in the double mutant mouse model multiple intestinal neoplasia X obese via disturbed glucose regulation and inflammation. J Obes. 2015;2015:343479. doi: 10.1155/2015/343479.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007;117(1):175–84. doi: 10.1172/JCI29881.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Nguyen MT, Favelyukis S, Nguyen AK, Reichart D, Scott PA, Jenn A, et al. A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways. J Biol Chem. 2007;282(48):35279–92. doi: 10.1074/jbc.M706762200.PubMedCrossRefGoogle Scholar
  42. 42.
    Strissel KJ, Stancheva Z, Miyoshi H, Perfield 2nd JW, DeFuria J, Jick Z, et al. Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes. 2007;56(12):2910–8. doi: 10.2337/db07-0767.PubMedCrossRefGoogle Scholar
  43. 43.
    Zaldivar F, McMurray RG, Nemet D, Galassetti P, Mills PJ, Cooper DM. Body fat and circulating leukocytes in children. Int J Obes (Lond). 2006;30(6):906–11. doi: 10.1038/sj.ijo.0803227.CrossRefGoogle Scholar
  44. 44.
    Debnath M, Agrawal S, Agrawal A, Dubey GP. Metaflammatory responses during obesity: pathomechanism and treatment. Obes Res Clin Pract. 2015. doi: 10.1016/j.orcp.2015.10.012.PubMedGoogle Scholar
  45. 45.
    Lumeng CN, Saltiel AR. Inflammatory links between obesity and metabolic disease. J Clin Invest. 2011;121(6):2111–7. doi: 10.1172/JCI57132.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Shore SA. Environmental perturbations: obesity. Compr Physiol. 2011;1(1):263–82. doi: 10.1002/cphy.c100017.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Atabek ME, Vatansev H, Erkul I. Oxidative stress in childhood obesity. J Pediatr Endocrinol Metab. 2004;17(8):1063–8.PubMedGoogle Scholar
  48. 48.
    Bakker SJ RGIJ, Teerlink T, Westerhoff HV, Gans RO, Heine RJ. Cytosolic triglycerides and oxidative stress in central obesity: the missing link between excessive atherosclerosis, endothelial dysfunction, and beta-cell failure? Atherosclerosis. 2000;148(1):17–21.PubMedCrossRefGoogle Scholar
  49. 49.
    Keaney Jr JF, Larson MG, Vasan RS, Wilson PW, Lipinska I, Corey D, et al. Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham Study. Arterioscler Thromb Vasc Biol. 2003;23(3):434–9. doi: 10.1161/01.ATV.0000058402.34138.11.PubMedCrossRefGoogle Scholar
  50. 50.
    Lee YS, Kim AY, Choi JW, Kim M, Yasue S, Son HJ, et al. Dysregulation of adipose glutathione peroxidase 3 in obesity contributes to local and systemic oxidative stress. Mol Endocrinol. 2008;22(9):2176–89. doi: 10.1210/me.2008-0023.PubMedCrossRefGoogle Scholar
  51. 51.
    Hernandez AR, Boada LD, Almeida-Gonzalez M, Mendoza Z, Ruiz-Suarez N, Valeron PF, et al. An estimation of the carcinogenic risk associated with the intake of multiple relevant carcinogens found in meat and charcuterie products. Sci Total Environ. 2015;514:33–41. doi: 10.1016/j.scitotenv.2015.01.108.PubMedCrossRefGoogle Scholar
  52. 52.
    Schut HA, Snyderwine EG. DNA adducts of heterocyclic amine food mutagens: implications for mutagenesis and carcinogenesis. Carcinogenesis. 1999;20(3):353–68.PubMedCrossRefGoogle Scholar
  53. 53.
    Pei YF, Tian Q, Zhang L, Deng HW. Exploring the major sources and extent of heterogeneity in a genome-wide association meta-analysis. Ann Hum Genet. 2015. doi: 10.1111/ahg.12143.PubMedGoogle Scholar
  54. 54.
    Holmes L, LaHurd A, Wasson E, McClarin L, Dabney K. Racial and ethnic heterogeneity in the association between total cholesterol and pediatric obesity. Int J Environ Res Public Health. 2015;13(1). doi: 10.3390/ijerph13010019.
  55. 55.
    Perl A. mTOR activation is a biomarker and a central pathway to autoimmune disorders, cancer, obesity, and aging. Ann N Y Acad Sci. 2015;1346(1):33–44. doi: 10.1111/nyas.12756.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Cowen S, McLaughlin SL, Hobbs G, Coad J, Martin KH, Olfert IM, et al. High-fat, high-calorie diet enhances mammary carcinogenesis and local inflammation in MMTV-PyMT mouse model of breast cancer. Cancers (Basel). 2015;7(3):1125–42. doi: 10.3390/cancers7030828.CrossRefGoogle Scholar
  57. 57.
    Crujeiras AB, Cabia B, Carreira MC, Amil M, Cueva J, Andrade S, et al. Secreted factors derived from obese visceral adipose tissue regulate the expression of breast malignant transformation genes. Int J Obes (Lond). 2015. doi: 10.1038/ijo.2015.208.Google Scholar
  58. 58.
    Gorlach A, Dimova EY, Petry A, Martinez-Ruiz A, Hernansanz-Agustin P, Rolo AP, et al. Reactive oxygen species, nutrition, hypoxia and diseases: problems solved? Redox Biol. 2015;6:372–85. doi: 10.1016/j.redox.2015.08.016.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Hasan S, Suhail N, Bilal N, Ashraf GM, Zaidi SK, AlNohair S, et al. Chronic unpredictable stress deteriorates the chemopreventive efficacy of pomegranate through oxidative stress pathway. Tumour Biol. 2015. doi: 10.1007/s13277-015-4469-9.Google Scholar
  60. 60.
    Manna P, Jain SK. Obesity, oxidative stress, adipose tissue dysfunction, and the associated health risks: causes and therapeutic strategies. Metab Syndr Relat Disord. 2015;13(10):423–44. doi: 10.1089/met.2015.0095.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Hunsche C, Hernandez O, De la Fuente M. Impaired immune response in old mice suffering from obesity and premature immunosenescence in adulthood. J Gerontol A Biol Sci Med Sci. 2015. doi: 10.1093/gerona/glv082.PubMedGoogle Scholar
  62. 62.
    Meyskens Jr FL, Farmer PJ, Anton-Culver H. Etiologic pathogenesis of melanoma: a unifying hypothesis for the missing attributable risk. Clin Cancer Res : Off J Am Assoc Cancer Res. 2004;10(8):2581–3.CrossRefGoogle Scholar
  63. 63.
    Caslin HL, Franco RL, Crabb EB, Huang CJ, Bowen MK, Acevedo EO. The effect of obesity on inflammatory cytokine and leptin production following acute mental stress. Psychophysiology. 2015. doi: 10.1111/psyp.12568.PubMedGoogle Scholar
  64. 64.
    Gogas H, Trakatelli M, Dessypris N, Terzidis A, Katsambas A, Chrousos GP, et al. Melanoma risk in association with serum leptin levels and lifestyle parameters: a case–control study. Ann Oncol. 2008;19(2):384–9. doi: 10.1093/annonc/mdm464.PubMedCrossRefGoogle Scholar
  65. 65.
    Dayakar A, Chandrasekaran S, Veronica J, Maurya RS. Leptin induces the phagocytosis and protective immune response in Leishmania donovani infected THP-1 cell line and human PBMCs. Exp Parasitol. 2015. doi: 10.1016/j.exppara.2015.12.002.Google Scholar
  66. 66.
    Huang CJ, McAllister MJ, Slusher AL, Webb HE, Mock JT, Acevedo EO. Obesity-related oxidative stress: the impact of physical activity and diet manipulation. Sports Med Open. 2015;1(1):32. doi: 10.1186/s40798-015-0031-y.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Mizutani H, Fukushima S, Masuguchi S, Yamashita J, Miyashita A, Nakahara S, et al. Serum levels of leptin receptor in patients with malignant melanoma as a new tumor marker. Exp Dermatol. 2013;22(11):748–9. doi: 10.1111/exd.12238.PubMedCrossRefGoogle Scholar
  68. 68.
    Chirumbolo S. The role of vitamin D towards immune tolerance in white adipose tissue (WAT). Endocr Metab Immune Disord Drug Targets. 2015;15(4):277–87.PubMedCrossRefGoogle Scholar
  69. 69.
    Yao Y, Zhu L, He L, Duan Y, Liang W, Nie Z, et al. A meta-analysis of the relationship between vitamin D deficiency and obesity. Int J Clin Exp Med. 2015;8(9):14977–84.PubMedPubMedCentralGoogle Scholar
  70. 70.
    Lagunova Z, Porojnicu AC, Grant WB, Bruland O, Moan JE. Obesity and increased risk of cancer: does decrease of serum 25-hydroxyvitamin D level with increasing body mass index explain some of the association? Mol Nutr Food Res. 2010;54(8):1127–33. doi: 10.1002/mnfr.200900512.PubMedGoogle Scholar
  71. 71.
    Kremer R, Campbell PP, Reinhardt T, Gilsanz V. Vitamin D status and its relationship to body fat, final height, and peak bone mass in young women. J Clin Endocrinol Metab. 2009;94(1):67–73. doi: 10.1210/jc.2008-1575.PubMedCrossRefGoogle Scholar
  72. 72.
    Bikle DD. Vitamin D, and the skin: physiology and pathophysiology. Rev Endocr Metab Disord. 2012;13(1):3–19.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004;79(3):362–71.PubMedGoogle Scholar
  74. 74.
    Lackey DE, Olefsky JM. Regulation of metabolism by the innate immune system. Nat Rev Endocrinol. 2016;12(1):15–28. doi: 10.1038/nrendo.2015.189.PubMedCrossRefGoogle Scholar
  75. 75.
    Zeyda M, Stulnig TM. Adipose tissue macrophages. Immunol Lett. 2007;112(2):61–7. doi: 10.1016/j.imlet.2007.07.003.PubMedCrossRefGoogle Scholar
  76. 76.
    De Pergola G, Silvestris F. Obesity as a major risk factor for cancer. J Obes. 2013;2013:291546. doi: 10.1155/2013/291546.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Saraiya A, Al-Shoha A, Brodell RT. Hyperinsulinemia associated with acanthosis nigricans, finger pebbles, acrochordons, and the sign of Leser-Trelat. Endocr Pract. 2013;19(3):522–5. doi: 10.4158/EP12192.RA.PubMedCrossRefGoogle Scholar
  78. 78.
    East HE, Subauste JS, Gandhi A, Koch CA. About secondary causes of diabetes mellitus. J Miss State Med Assoc. 2012;53(11):380–3.PubMedGoogle Scholar
  79. 79.
    Cheng S, Gomez K, Serri O, Chik C, Ezzat S. The role of diabetes in acromegaly associated neoplasia. PLoS One. 2015;10(5), e0127276. doi: 10.1371/journal.pone.0127276.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Su Y, Carey LC, Rose JC, Pulgar VM. Leptin alters adrenal responsiveness by decreasing expression of ACTH-R, StAR, and P450c21 in hypoxemic fetal sheep. Reprod Sci. 2012;19(10):1075–84. doi: 10.1177/1933719112442246.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Ellerhorst JA, Diwan AH, Dang SM, Uffort DG, Johnson MK, Cooke CP, et al. Promotion of melanoma growth by the metabolic hormone leptin. Oncol Rep. 2010;23(4):901–7.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    de Vries E, Coebergh JW. Cutaneous malignant melanoma in Europe. Eur J Cancer. 2004;40(16):2355–66. doi: 10.1016/j.ejca.2004.06.003.PubMedCrossRefGoogle Scholar
  83. 83.
    Lasithiotakis KG, Leiter U, Gorkievicz R, Eigentler T, Breuninger H, Metzler G, et al. The incidence and mortality of cutaneous melanoma in Southern Germany: trends by anatomic site and pathologic characteristics, 1976 to 2003. Cancer. 2006;107(6):1331–9. doi: 10.1002/cncr.22126.PubMedCrossRefGoogle Scholar
  84. 84.
    Mansson-Brahme E, Johansson H, Larsson O, Rutqvist LE, Ringborg U. Trends in incidence of cutaneous malignant melanoma in a Swedish population 1976–1994. Acta Oncol. 2002;41(2):138–46.PubMedCrossRefGoogle Scholar
  85. 85.
    Stang A, Pukkala E, Sankila R, Soderman B, Hakulinen T. Time trend analysis of the skin melanoma incidence of Finland from 1953 through 2003 including 16,414 cases. Int J Cancer. 2006;119(2):380–4. doi: 10.1002/ijc.21836.PubMedCrossRefGoogle Scholar
  86. 86.
    Linos E, Swetter SM, Cockburn MG, Colditz GA, Clarke CA. Increasing burden of melanoma in the United States. J Invest Dermatol. 2009;129(7):1666–74. doi: 10.1038/jid.2008.423.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Ortiz CA, Goodwin JS, Freeman JL. The effect of socioeconomic factors on incidence, stage at diagnosis and survival of cutaneous melanoma. Med Sci Monit. 2005;11(5):RA163–72.PubMedGoogle Scholar
  88. 88.
    Pollitt RA, Clarke CA, Shema SJ, Swetter SM. California Medicaid enrollment and melanoma stage at diagnosis: a population-based study. Am J Prev Med. 2008;35(1):7–13. doi: 10.1016/j.amepre.2008.03.026.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Roetzheim RG, Pal N, Tennant C, Voti L, Ayanian JZ, Schwabe A, et al. Effects of health insurance and race on early detection of cancer. J Natl Cancer Inst. 1999;91(16):1409–15.PubMedCrossRefGoogle Scholar
  90. 90.
    Diffey B. Climate change, ozone depletion and the impact on ultraviolet exposure of human skin. Phys Med Biol. 2004;49(1):R1–11.PubMedCrossRefGoogle Scholar
  91. 91.
    Welch HG, Woloshin S, Schwartz LM. Skin biopsy rates and incidence of melanoma: population based ecological study. BMJ. 2005;331(7515):481. doi: 10.1136/bmj.38516.649537.E0.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Hall HI, Jamison P, Fulton JP, Clutter G, Roffers S, Parrish P. Reporting cutaneous melanoma to cancer registries in the United States. J Am Acad Dermatol. 2003;49(4):624–30.PubMedCrossRefGoogle Scholar
  93. 93.
    Swerlick RA, Chen S. The melanoma epidemic. Is increased surveillance the solution or the problem? Arch Dermatol. 1996;132(8):881–4.PubMedCrossRefGoogle Scholar
  94. 94.
    Swerlick RA, Chen S. The melanoma epidemic: more apparent than real? Mayo Clin Proc. 1997;72(6):559–64. doi: 10.1016/S0025-6196(11)63306-5.PubMedCrossRefGoogle Scholar
  95. 95.
    Olsen CM, Carroll HJ, Whiteman DC. Estimating the attributable fraction for cancer: a meta-analysis of nevi and melanoma. Cancer Prev Res (Phila). 2010;3(2):233–45. doi: 10.1158/1940-6207.CAPR-09-0108.CrossRefGoogle Scholar
  96. 96.
    Gandini S, Sera F, Cattaruzza MS, Pasquini P, Zanetti R, Masini C, et al. Meta-analysis of risk factors for cutaneous melanoma: III. Family history, actinic damage and phenotypic factors. Eur J Cancer. 2005;41(14):2040–59. doi: 10.1016/j.ejca.2005.03.034.PubMedCrossRefGoogle Scholar
  97. 97.
    Wheless L, Black J, Alberg AJ. Nonmelanoma skin cancer and the risk of second primary cancers: a systematic review. Cancer Epidemiol Biomarkers Prev. 2010;19(7):1686–95. doi: 10.1158/1055-9965.EPI-10-0243.PubMedCrossRefGoogle Scholar
  98. 98.
    Chen ST, Geller AC, Tsao H. Update on the epidemiology of melanoma. Curr Dermatol Rep. 2013;2(1):24–34. doi: 10.1007/s13671-012-0035-5.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Pappo AS, Armstrong GT, Liu W, Srivastava DK, McDonald A, Leisenring WM, et al. Melanoma as a subsequent neoplasm in adult survivors of childhood cancer: a report from the childhood cancer survivor study. Pediatr Blood Cancer. 2013;60(3):461–6. doi: 10.1002/pbc.24266.PubMedCrossRefGoogle Scholar
  100. 100.
    Gandini S, Sera F, Cattaruzza MS, Pasquini P, Picconi O, Boyle P, et al. Meta-analysis of risk factors for cutaneous melanoma: II. Sun exposure. Eur J Cancer. 2005;41(1):45–60. doi: 10.1016/j.ejca.2004.10.016.PubMedCrossRefGoogle Scholar
  101. 101.
    Rigel DS, Rigel EG, Rigel AC. Effects of altitude and latitude on ambient UVB radiation. J Am Acad Dermatol. 1999;40(1):114–6.PubMedCrossRefGoogle Scholar
  102. 102.
    Bulliard JL. Site-specific risk of cutaneous malignant melanoma and pattern of sun exposure in New Zealand. Int J Cancer. 2000;85(5):627–32.PubMedCrossRefGoogle Scholar
  103. 103.
    Parisi AV, Kimlin MG, Lester R, Turnbull D. Lower body anatomical distribution of solar ultraviolet radiation on the human form in standing and sitting postures. J Photochem Photobiol B. 2003;69(1):1–6.PubMedCrossRefGoogle Scholar
  104. 104.
    Reed KB, Brewer JD, Lohse CM, Bringe KE, Pruitt CN, Gibson LE. Increasing incidence of melanoma among young adults: an epidemiological study in Olmsted County. Minnesota Mayo Clin Proc. 2012;87(4):328–34. doi: 10.1016/j.mayocp.2012.01.010.PubMedCrossRefGoogle Scholar
  105. 105.
    Stryker WS, Stampfer MJ, Stein EA, Kaplan L, Louis TA, Sober A, et al. Diet, plasma levels of beta-carotene and alpha-tocopherol, and risk of malignant melanoma. Am J Epidemiol. 1990;131(4):597–611.PubMedGoogle Scholar
  106. 106.
    Bain C, Green A, Siskind V, Alexander J, Harvey P. Diet and melanoma. An exploratory case–control study. Ann Epidemiol. 1993;3(3):235–8.PubMedCrossRefGoogle Scholar
  107. 107.
    Millen AE, Tucker MA, Hartge P, Halpern A, Elder DE, Guerry D, et al. Diet and melanoma in a case–control study. Cancer Epidemiol Biomarkers Prev. 2004;13(6):1042–51.PubMedGoogle Scholar
  108. 108.
    Meyskens Jr FL, Farmer PJ, Anton-Culver H. Diet and melanoma in a case–control study. Cancer Epidemiol Biomarkers Prev. 2005;14(1):293.PubMedGoogle Scholar
  109. 109.
    Le Marchand L, Saltzman BS, Hankin JH, Wilkens LR, Franke AA, Morris SJ, et al. Sun exposure, diet, and melanoma in Hawaii Caucasians. Am J Epidemiol. 2006;164(3):232–45. doi: 10.1093/aje/kwj115.PubMedCrossRefGoogle Scholar
  110. 110.
    Nicolopoulou-Stamati P, Hens L, Sasco AJ. Cosmetics as endocrine disruptors: are they a health risk? Rev Endocr Metab Disord. 2015;16(4):373–83.PubMedCrossRefGoogle Scholar
  111. 111.
    Holland KT, Bojar RA. Cosmetics: what is their influence on the skin microflora? Am J Clin Dermatol. 2002;3(7):445–9.PubMedCrossRefGoogle Scholar
  112. 112.
    Karpuzoglu E, Holladay SD, Gogal Jr RM. Parabens: potential impact of low-affinity estrogen receptor binding chemicals on human health. J Toxicol Environ Health B Crit Rev. 2013;16(5):321–35. doi: 10.1080/10937404.2013.809252.PubMedCrossRefGoogle Scholar
  113. 113.
    Gandini S, Iodice S, Koomen E, Di Pietro A, Sera F, Caini S. Hormonal and reproductive factors in relation to melanoma in women: current review and meta-analysis. Eur J Cancer. 2011;47(17):2607–17. doi: 10.1016/j.ejca.2011.04.023.PubMedCrossRefGoogle Scholar
  114. 114.
    Ward EM, Burnett CA, Ruder A, Davis-King K. Industries and cancer. Cancer Causes Control. 1997;8(3):356–70.PubMedCrossRefGoogle Scholar
  115. 115.
    Sinks T, Steele G, Smith AB, Watkins K, Shults RA. Mortality among workers exposed to polychlorinated biphenyls. Am J Epidemiol. 1992;136(4):389–98.PubMedGoogle Scholar
  116. 116.
    Loomis D, Browning SR, Schenck AP, Gregory E, Savitz DA. Cancer mortality among electric utility workers exposed to polychlorinated biphenyls. Occup Environ Med. 1997;54(10):720–8.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Robinson CF, Petersen M, Palu S. Mortality patterns among electrical workers employed in the U.S. construction industry, 1982–1987. Am J Ind Med. 1999;36(6):630–7.PubMedCrossRefGoogle Scholar
  118. 118.
    Nelemans PJ, Scholte R, Groenendal H, Kiemeney LA, Rampen FH, Ruiter DJ, et al. Melanoma and occupation: results of a case–control study in The Netherlands. Br J Ind Med. 1993;50(7):642–6.PubMedPubMedCentralGoogle Scholar
  119. 119.
    Gantz I, Fong TM. The melanocortin system. Am J Physiol Endocrinol Metab. 2003;284(3):E468–74. doi: 10.1152/ajpendo.00434.2002.PubMedCrossRefGoogle Scholar
  120. 120.
    Danforth CH. Hereditary adiposity in mice. Obes Res. 1996;4(1):96–100.PubMedCrossRefGoogle Scholar
  121. 121.
    Dickies MM. A new viable yellow mutation in the house mouse. J Hered. 1962;53:84–6.PubMedGoogle Scholar
  122. 122.
    Heston WE, Vlahakis G. Influence of the Ay gene on mammary-gland tumors, hepatomas, and normal growth in mice. J Natl Cancer Inst. 1961;26:969–83.PubMedGoogle Scholar
  123. 123.
    Heston WE, Vlahakis G. C3H-Avy—a high hepatoma and high mammary tumor strain of mice. J Natl Cancer Inst. 1968;40(6):1161–6.PubMedGoogle Scholar
  124. 124.
    Yen TT, Gill AM, Frigeri LG, Barsh GS, Wolff GL. Obesity, diabetes, and neoplasia in yellow A(vy)/- mice: ectopic expression of the agouti gene. FASEB J. 1994;8(8):479–88.PubMedGoogle Scholar
  125. 125.
    Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gruters A. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet. 1998;19(2):155–7. doi: 10.1038/509.PubMedCrossRefGoogle Scholar
  126. 126.
    Millington GW. Proopiomelanocortin (POMC): the cutaneous roles of its melanocortin products and receptors. Clin Exp Dermatol. 2006;31(3):407–12. doi: 10.1111/j.1365-2230.2006.02128.x.PubMedCrossRefGoogle Scholar
  127. 127.
    Ramachandrappa S, Farooqi IS. Genetic approaches to understanding human obesity. J Clin Invest. 2011;121(6):2080–6. doi: 10.1172/JCI46044.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    D’Orazio JA, Nobuhisa T, Cui R, Arya M, Spry M, Wakamatsu K, et al. Topical drug rescue strategy and skin protection based on the role of Mc1r in UV-induced tanning. Nature. 2006;443(7109):340–4. doi: 10.1038/nature05098.PubMedCrossRefGoogle Scholar
  129. 129.
    Cui R, Widlund HR, Feige E, Lin JY, Wilensky DL, Igras VE, et al. Central role of p53 in the suntan response and pathologic hyperpigmentation. Cell. 2007;128(5):853–64. doi: 10.1016/j.cell.2006.12.045.PubMedCrossRefGoogle Scholar
  130. 130.
    Sato HNY, Chrousos GP, Ichihashi M, Funasak Y. The expression of corticotropin-releasing hormone in melanoma. Pigment Cell Res. 2002;15(2):98–103.PubMedCrossRefGoogle Scholar
  131. 131.
    Millington GW. The role of proopiomelanocortin (POMC) neurones in feeding behaviour. Nutr Metab (Lond). 2007;4:18. doi: 10.1186/1743-7075-4-18.CrossRefGoogle Scholar
  132. 132.
    Sharma SD, Katiyar SK. Leptin deficiency-induced obesity exacerbates ultraviolet B radiation-induced cyclooxygenase-2 expression and cell survival signals in ultraviolet B-irradiated mouse skin. Toxicol Appl Pharmacol. 2010;244(3):328–35. doi: 10.1016/j.taap.2010.01.010.PubMedCrossRefGoogle Scholar
  133. 133.
    Akbani R, Akdemir KC, Aksoy BA, Albert M, Ally A, Amin SB, et al. Genomic classification of cutaneous melanoma. Cell. 2015;161(7):1681–96. doi: 10.1016/j.cell.2015.05.044.CrossRefGoogle Scholar
  134. 134.
    Garofalo C, Surmacz E. Leptin and cancer. J Cell Physiol. 2006;207(1):12–22. doi: 10.1002/jcp.20472.PubMedCrossRefGoogle Scholar
  135. 135.
    Tessitore L, Vizio B, Jenkins O, De Stefano I, Ritossa C, Argiles JM, et al. Leptin expression in colorectal and breast cancer patients. Int J Mol Med. 2000;5(4):421–6.PubMedGoogle Scholar
  136. 136.
    Petridou E, Belechri M, Dessypris N, Koukoulomatis P, Diakomanolis E, Spanos E, et al. Leptin and body mass index in relation to endometrial cancer risk. Ann Nutr Metab. 2002;46(3–4):147–51.PubMedCrossRefGoogle Scholar
  137. 137.
    Stattin P, Palmqvist R, Soderberg S, Biessy C, Ardnor B, Hallmans G, et al. Plasma leptin and colorectal cancer risk: a prospective study in Northern Sweden. Oncol Rep. 2003;10(6):2015–21.PubMedGoogle Scholar
  138. 138.
    Arnardottir ES, Maislin G, Jackson N, Schwab RJ, Benediktsdottir B, Teff K, et al. The role of obesity, different fat compartments and sleep apnea severity in circulating leptin levels: the Icelandic Sleep Apnea Cohort study. Int J Obes (Lond). 2013;37(6):835–42. doi: 10.1038/ijo.2012.138.CrossRefGoogle Scholar
  139. 139.
    Leroy P, Dessolin S, Villageois P, Moon BC, Friedman JM, Ailhaud G, et al. Expression of ob gene in adipose cells. Regulation by insulin. J Biol Chem. 1996;271(5):2365–8.PubMedCrossRefGoogle Scholar
  140. 140.
    Zhang HH, Kumar S, Barnett AH, Eggo MC. Tumour necrosis factor-alpha exerts dual effects on human adipose leptin synthesis and release. Mol Cell Endocrinol. 2000;159(1–2):79–88.PubMedCrossRefGoogle Scholar
  141. 141.
    Dagogo-Jack S, Selke G, Melson AK, Newcomer JW. Robust leptin secretory responses to dexamethasone in obese subjects. J Clin Endocrinol Metab. 1997;82(10):3230–3. doi: 10.1210/jcem.82.10.4154.PubMedGoogle Scholar
  142. 142.
    Machinal-Quelin F, Dieudonne MN, Pecquery R, Leneveu MC, Giudicelli Y. Direct in vitro effects of androgens and estrogens on ob gene expression and leptin secretion in human adipose tissue. Endocrine. 2002;18(2):179–84. doi: 10.1385/ENDO:18:2:179.PubMedCrossRefGoogle Scholar
  143. 143.
    Fain JN, Leffler CW, Bahouth SW. Eicosanoids as endogenous regulators of leptin release and lipolysis by mouse adipose tissue in primary culture. J Lipid Res. 2000;41(10):1689–94.PubMedGoogle Scholar
  144. 144.
    Oba J, Wei W, Gershenwald JE, Johnson MM, Wyatt CM, Ellerhorst JA, et al. Elevated serum leptin levels are associated with an increased risk of sentinel lymph node metastasis in cutaneous melanoma. Medicine (Baltimore). 2016;95(11), e3073. doi: 10.1097/MD.0000000000003073.CrossRefGoogle Scholar
  145. 145.
    Jung JI, Cho HJ, Jung YJ, Kwon SH, Her S, Choi SS, et al. High-fat diet-induced obesity increases lymphangiogenesis and lymph node metastasis in the B16F10 melanoma allograft model: roles of adipocytes and M2-macrophages. Int J Cancer. 2015;136(2):258–70. doi: 10.1002/ijc.28983.PubMedCrossRefGoogle Scholar
  146. 146.
    McMurphy T, Xiao R, Magee D, Slater A, Zabeau L, Tavernier J, et al. The anti-tumor activity of a neutralizing nanobody targeting leptin receptor in a mouse model of melanoma. PLoS ONE. 2014;9(2), e89895. doi: 10.1371/journal.pone.0089895.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Emilsson V, Liu YL, Cawthorne MA, Morton NM, Davenport M. Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion. Diabetes. 1997;46(2):313–6.PubMedCrossRefGoogle Scholar
  148. 148.
    Kulkarni RN, Wang ZL, Wang RM, Hurley JD, Smith DM, Ghatei MA, et al. Leptin rapidly suppresses insulin release from insulinoma cells, rat and human islets, and in vivo, in mice. J Clin Invest. 1997;100(11):2729–36. doi: 10.1172/JCI119818.PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Morris DL, Rui L. Recent advances in understanding leptin signaling and leptin resistance. Am J Physiol Endocrinol Metab. 2009;297(6):E1247–59. doi: 10.1152/ajpendo.00274.2009.PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Wang MY, Lee Y, Unger RH. Novel form of lipolysis induced by leptin. J Biol Chem. 1999;274(25):17541–4.PubMedCrossRefGoogle Scholar
  151. 151.
    Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science. 1995;269(5223):546–9.PubMedCrossRefGoogle Scholar
  152. 152.
    Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 1995;269(5223):543–6.PubMedCrossRefGoogle Scholar
  153. 153.
    Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science. 1995;269(5223):540–3.PubMedCrossRefGoogle Scholar
  154. 154.
    Stephens TW, Basinski M, Bristow PK, Bue-Valleskey JM, Burgett SG, Craft L, et al. The role of neuropeptide Y in the antiobesity action of the obese gene product. Nature. 1995;377(6549):530–2. doi: 10.1038/377530a0.PubMedCrossRefGoogle Scholar
  155. 155.
    Caro JF, Kolaczynski JW, Nyce MR, Ohannesian JP, Opentanova I, Goldman WH, et al. Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet. 1996;348(9021):159–61.PubMedCrossRefGoogle Scholar
  156. 156.
    El-Haschimi K, Pierroz DD, Hileman SM, Bjorbaek C, Flier JS. Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity. J Clin Invest. 2000;105(12):1827–32. doi: 10.1172/JCI9842.PubMedPubMedCentralCrossRefGoogle Scholar
  157. 157.
    Schwartz MW, Peskind E, Raskind M, Boyko EJ, Porte Jr D. Cerebrospinal fluid leptin levels: relationship to plasma levels and to adiposity in humans. Nat Med. 1996;2(5):589–93.PubMedCrossRefGoogle Scholar
  158. 158.
    Belouzard S, Delcroix D, Rouille Y. Low levels of expression of leptin receptor at the cell surface result from constitutive endocytosis and intracellular retention in the biosynthetic pathway. J Biol Chem. 2004;279(27):28499–508. doi: 10.1074/jbc.M400508200.PubMedCrossRefGoogle Scholar
  159. 159.
    Diano S, Kalra SP, Horvath TL. Leptin receptor immunoreactivity is associated with the Golgi apparatus of hypothalamic neurons and glial cells. J Neuroendocrinol. 1998;10(9):647–50.PubMedCrossRefGoogle Scholar
  160. 160.
    Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. 1997;387(6636):903–8. doi: 10.1038/43185.PubMedCrossRefGoogle Scholar
  161. 161.
    Strobel A, Issad T, Camoin L, Ozata M, Strosberg AD. A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet. 1998;18(3):213–5. doi: 10.1038/ng0398-213.PubMedCrossRefGoogle Scholar
  162. 162.
    Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372(6505):425–32. doi: 10.1038/372425a0.PubMedCrossRefGoogle Scholar
  163. 163.
    Martin SS, Qasim A, Reilly MP. Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease. J Am Coll Cardiol. 2008;52(15):1201–10. doi: 10.1016/j.jacc.2008.05.060.PubMedPubMedCentralCrossRefGoogle Scholar
  164. 164.
    Mantzoros CS, Liolios AD, Tritos NA, Kaklamani VG, Doulgerakis DE, Griveas I, et al. Circulating insulin concentrations, smoking, and alcohol intake are important independent predictors of leptin in young healthy men. Obes Res. 1998;6(3):179–86.PubMedCrossRefGoogle Scholar
  165. 165.
    Traish AM, Zitzmann M. The complex and multifactorial relationship between testosterone deficiency (TD), obesity and vascular disease. Rev Endocr Metab Disord. 2015;16(3):249–68. doi: 10.1007/s11154-015-9323-2.PubMedCrossRefGoogle Scholar
  166. 166.
    Ullah MI, Washington T, Kazi M, Tamanna S, Koch CA. Testosterone deficiency as a risk factor for cardiovascular disease. Horm Metab Res. 2011;43(03):153–64.PubMedCrossRefGoogle Scholar
  167. 167.
    Coppari R, Bjorbaek C. Leptin revisited: its mechanism of action and potential for treating diabetes. Nat Rev Drug Discov. 2012;11(9):692–708. doi: 10.1038/nrd3757.PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Stanley BG, Leibowitz SF. Neuropeptide Y injected in the paraventricular hypothalamus: a powerful stimulant of feeding behavior. Proc Natl Acad Sci U S A. 1985;82(11):3940–3.PubMedPubMedCentralCrossRefGoogle Scholar
  169. 169.
    Ozcan L, Ergin AS, Lu A, Chung J, Sarkar S, Nie D, et al. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab. 2009;9(1):35–51. doi: 10.1016/j.cmet.2008.12.004.PubMedCrossRefGoogle Scholar
  170. 170.
    Zhang X, Zhang G, Zhang H, Karin M, Bai H, Cai D. Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell. 2008;135(1):61–73. doi: 10.1016/j.cell.2008.07.043.PubMedPubMedCentralCrossRefGoogle Scholar
  171. 171.
    Ogimoto K, Harris Jr MK, Wisse BE. MyD88 is a key mediator of anorexia, but not weight loss, induced by lipopolysaccharide and interleukin-1 beta. Endocrinology. 2006;147(9):4445–53. doi: 10.1210/en.2006-0465.PubMedCrossRefGoogle Scholar
  172. 172.
    Ozcan U, Ozcan L, Yilmaz E, Duvel K, Sahin M, Manning BD, et al. Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis. Mol Cell. 2008;29(5):541–51. doi: 10.1016/j.molcel.2007.12.023.PubMedPubMedCentralCrossRefGoogle Scholar
  173. 173.
    Hosoi T, Sasaki M, Miyahara T, Hashimoto C, Matsuo S, Yoshii M, et al. Endoplasmic reticulum stress induces leptin resistance. Mol Pharmacol. 2008;74(6):1610–9. doi: 10.1124/mol.108.050070.PubMedCrossRefGoogle Scholar
  174. 174.
    Lam QL, Lu L. Role of leptin in immunity. Cell Mol Immunol. 2007;4(1):1–13.PubMedGoogle Scholar
  175. 175.
    Chen K, Li F, Li J, Cai H, Strom S, Bisello A, et al. Induction of leptin resistance through direct interaction of C-reactive protein with leptin. Nat Med. 2006;12(4):425–32. doi: 10.1038/nm1372.PubMedCrossRefGoogle Scholar
  176. 176.
    Amjadi F, Javanmard SH, Zarkesh-Esfahani H, Khazaei M, Narimani M. Leptin promotes melanoma tumor growth in mice related to increasing circulating endothelial progenitor cells numbers and plasma NO production. J Exp Clin Cancer Res. 2011;30:21. doi: 10.1186/1756-9966-30-21.PubMedPubMedCentralCrossRefGoogle Scholar
  177. 177.
    Dome B, Hendrix MJ, Paku S, Tovari J, Timar J. Alternative vascularization mechanisms in cancer: pathology and therapeutic implications. Am J Pathol. 2007;170(1):1–15. doi: 10.2353/ajpath.2007.060302.PubMedPubMedCentralCrossRefGoogle Scholar
  178. 178.
    Gonzalez RR, Cherfils S, Escobar M, Yoo JH, Carino C, Styer AK, et al. Leptin signaling promotes the growth of mammary tumors and increases the expression of vascular endothelial growth factor (VEGF) and its receptor type two (VEGF-R2). J Biol Chem. 2006;281(36):26320–8. doi: 10.1074/jbc.M601991200.PubMedCrossRefGoogle Scholar
  179. 179.
    Ribatti D, Nico B, Belloni AS, Vacca A, Roncali L, Nussdorfer GG. Angiogenic activity of leptin in the chick embryo chorioallantoic membrane is in part mediated by endogenous fibroblast growth factor-2. Int J Mol Med. 2001;8(3):265–8.PubMedGoogle Scholar
  180. 180.
    Lago R, Gomez R, Lago F, Gomez-Reino J, Gualillo O. Leptin beyond body weight regulation—current concepts concerning its role in immune function and inflammation. Cell Immunol. 2008;252(1–2):139–45. doi: 10.1016/j.cellimm.2007.09.004.PubMedCrossRefGoogle Scholar
  181. 181.
    Artwohl M, Roden M, Holzenbein T, Freudenthaler A, Waldhausl W, Baumgartner-Parzer SM. Modulation by leptin of proliferation and apoptosis in vascular endothelial cells. Int J Obes Relat Metab Disord. 2002;26(4):577–80.PubMedCrossRefGoogle Scholar
  182. 182.
    Ahima RS, Flier JS. Leptin. Annu Rev Physiol. 2000;62:413–37. doi: 10.1146/annurev.physiol.62.1.413.PubMedCrossRefGoogle Scholar
  183. 183.
    Grosfeld A, Andre J, Hauguel-De Mouzon S, Berra E, Pouyssegur J, Guerre-Millo M. Hypoxia-inducible factor 1 transactivates the human leptin gene promoter. J Biol Chem. 2002;277(45):42953–7. doi: 10.1074/jbc.M206775200.PubMedCrossRefGoogle Scholar
  184. 184.
    Brakenhielm E, Veitonmaki N, Cao R, Kihara S, Matsuzawa Y, Zhivotovsky B, et al. Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci U S A. 2004;101(8):2476–81.PubMedPubMedCentralCrossRefGoogle Scholar
  185. 185.
    Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood. 2000;96(5):1723–32.PubMedGoogle Scholar
  186. 186.
    Kang JH, Lee YY, Yu BY, Yang BS, Cho KH, Yoon DK, et al. Adiponectin induces growth arrest and apoptosis of MDA-MB-231 breast cancer cell. Arch Pharm Res. 2005;28(11):1263–9.PubMedCrossRefGoogle Scholar
  187. 187.
    Ogunwobi OO, Beales IL. Adiponectin stimulates proliferation and cytokine secretion in colonic epithelial cells. Regul Pept. 2006;134(2–3):105–13. doi: 10.1016/j.regpep.2006.02.001.PubMedCrossRefGoogle Scholar
  188. 188.
    Bub JD, Miyazaki T, Iwamoto Y. Adiponectin as a growth inhibitor in prostate cancer cells. Biochem Biophys Res Commun. 2006;340(4):1158–66. doi: 10.1016/j.bbrc.2005.12.103.PubMedCrossRefGoogle Scholar
  189. 189.
    Arditi JD, Venihaki M, Karalis KP, Chrousos GP. Antiproliferative effect of adiponectin on MCF7 breast cancer cells: a potential hormonal link between obesity and cancer. Horm Metab Res. 2007;39(1):9–13. doi: 10.1055/s-2007-956518.PubMedCrossRefGoogle Scholar
  190. 190.
    Mantzoros CS, Trakatelli M, Gogas H, Dessypris N, Stratigos A, Chrousos GP, et al. Circulating adiponectin levels in relation to melanoma: a case–control study. Eur J Cancer. 2007;43(9):1430–6. doi: 10.1016/j.ejca.2007.03.026.PubMedCrossRefGoogle Scholar
  191. 191.
    Gallagher EJ, Fierz Y, Ferguson RD, LeRoith D. The pathway from diabetes and obesity to cancer, on the route to targeted therapy. Endocr Pract. 2010;16(5):864–73. doi: 10.4158/EP10098.RA.PubMedCrossRefGoogle Scholar
  192. 192.
    Moore T, Carbajal S, Beltran L, Perkins SN, Yakar S, Leroith D, et al. Reduced susceptibility to two-stage skin carcinogenesis in mice with low circulating insulin-like growth factor I levels. Cancer Res. 2008;68(10):2680–8.CrossRefGoogle Scholar
  193. 193.
    Sadagurski MYS, Weingarten G, Holzenberger M, Rhodes CJ, Breitkreutz D, Leroith D, et al. Insulin-like growth factor 1 receptor signaling regulates skin development and inhibits skin keratinocyte differentiation. Mol Cell Biol. 2006;26(7):2675–87.PubMedPubMedCentralCrossRefGoogle Scholar
  194. 194.
    Chi M, Ye Y, Zhang XD, Chen J. Insulin induces drug resistance in melanoma through activation of the PI3K/Akt pathway. Drug Des Devel Ther. 2014;8:255–62. doi: 10.2147/DDDT.S53568.PubMedPubMedCentralGoogle Scholar
  195. 195.
    Kucera R, Treskova I, Vrzalova J, Svobodova S, Topolcan O, Fuchsova R, et al. Evaluation of IGF1 serum levels in malignant melanoma and healthy subjects. Anticancer Res. 2014;34(9):5217–20.PubMedGoogle Scholar
  196. 196.
    Naspi A, Panasiti V, Abbate F, Roberti V, Devirgiliis V, Curzio M, et al. Insulin-like-growth-factor-binding-protein-3 (IGFBP-3) contrasts melanoma progression in vitro and in vivo. PLoS One. 2014;9(6), e98641. doi: 10.1371/journal.pone.0098641.PubMedPubMedCentralCrossRefGoogle Scholar
  197. 197.
    Jones SA, Morand EF. Glucocorticoids in 2015: new answers to old problems. Nat Rev Rheumatol. 2015. doi: 10.1038/nrrheum.2015.176.Google Scholar
  198. 198.
    Bhakoo HS, Milholland RJ, Lopez R, Karakousis C, Rosen F. High incidence and characterization of glucocorticoid receptors in human malignant melanoma. J Natl Cancer Inst. 1981;66(1):21–5.PubMedGoogle Scholar
  199. 199.
    Dobos J, Kenessey I, Timar J, Ladanyi A. Glucocorticoid receptor expression and antiproliferative effect of dexamethasone on human melanoma cells. Pathol Oncol Res. 2011;17(3):729–34. doi: 10.1007/s12253-011-9377-8.PubMedCrossRefGoogle Scholar
  200. 200.
    Spencer SJ, Tilbrook A. The glucocorticoid contribution to obesity. Stress. 2011;14(3):233–46. doi: 10.3109/10253890.2010.534831.PubMedCrossRefGoogle Scholar
  201. 201.
    Livingstone DE, Jones GC, Smith K, Jamieson PM, Andrew R, Kenyon CJ, et al. Understanding the role of glucocorticoids in obesity: tissue-specific alterations of corticosterone metabolism in obese Zucker rats. Endocrinology. 2000;141(2):560–3. doi: 10.1210/endo.141.2.7297.PubMedGoogle Scholar
  202. 202.
    Shoag J, Haq R, Zhang M, Liu L, Rowe GC, Jiang A, et al. PGC-1 coactivators regulate MITF and the tanning response. Mol Cell. 2013;49(1):145–57. doi: 10.1016/j.molcel.2012.10.027.PubMedCrossRefGoogle Scholar
  203. 203.
    Price RA, Li WD, Zhao H. FTO gene SNPs associated with extreme obesity in cases, controls and extremely discordant sister pairs. BMC Med Genet. 2008;9:4. doi: 10.1186/1471-2350-9-4.PubMedPubMedCentralCrossRefGoogle Scholar
  204. 204.
    Ghosh S, Murinova L, Trnovec T, Loffredo CA, Washington K, Mitra PS, et al. Biomarkers linking PCB exposure and obesity. Curr Pharm Biotechnol. 2014;15(11):1058–68.PubMedPubMedCentralCrossRefGoogle Scholar
  205. 205.
    De Coster S, van Larebeke N. Endocrine-disrupting chemicals: associated disorders and mechanisms of action. J Environ Public Health. 2012;2012:713696. doi: 10.1155/2012/713696.PubMedPubMedCentralCrossRefGoogle Scholar
  206. 206.
    Koch CA. EDITORIAL: “The Koch’s” view on the sense of taste in endocrinology. Rev Endocr Metab Disord. 2016;17(2):143–7. doi: 10.1007/s11154-016-9383-y.PubMedCrossRefGoogle Scholar
  207. 207.
    Brill MJ, Diepstraten J, van Rongen A, van Kralingen S, van den Anker JN, Knibbe CA. Impact of obesity on drug metabolism and elimination in adults and children. Clin Pharmacokinet. 2012;51(5):277–304. doi: 10.2165/11599410-000000000-00000.PubMedCrossRefGoogle Scholar
  208. 208.
    James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507–20. doi: 10.1001/jama.2013.284427.PubMedCrossRefGoogle Scholar
  209. 209.
    McDonald E, Freedman DM, Alexander BH, Doody MM, Tucker MA, Linet MS, et al. Prescription diuretic use and risk of basal cell carcinoma in the nationwide U.S. radiologic technologists cohort. Cancer Epidemiol Biomarkers Prev. 2014;23(8):1539–45. doi: 10.1158/1055-9965.EPI-14-0251.PubMedPubMedCentralCrossRefGoogle Scholar
  210. 210.
    Robinson SN, Zens MS, Perry AE, Spencer SK, Duell EJ, Karagas MR. Photosensitizing agents and the risk of non-melanoma skin cancer: a population-based case–control study. J Invest Dermatol. 2013;133(8):1950–5. doi: 10.1038/jid.2013.33.PubMedPubMedCentralCrossRefGoogle Scholar
  211. 211.
    Kaae J, Boyd HA, Hansen AV, Wulf HC, Wohlfahrt J, Melbye M. Photosensitizing medication use and risk of skin cancer. Cancer Epidemiol Biomarkers Prev. 2010;19(11):2942–9. doi: 10.1158/1055-9965.EPI-10-0652.PubMedCrossRefGoogle Scholar
  212. 212.
    Ruiter R, Visser LE, Eijgelsheim M, Rodenburg EM, Hofman A, Coebergh JW, et al. High-ceiling diuretics are associated with an increased risk of basal cell carcinoma in a population-based follow-up study. Eur J Cancer. 2010;46(13):2467–72. doi: 10.1016/j.ejca.2010.04.024.PubMedCrossRefGoogle Scholar
  213. 213.
    Glatz M, Hofbauer GF. Phototoxic and photoallergic cutaneous drug reactions. Chem Immunol Allergy. 2012;97:167–79. doi: 10.1159/000335630.PubMedCrossRefGoogle Scholar
  214. 214.
    Moore DE. Drug-induced cutaneous photosensitivity: incidence, mechanism, prevention and management. Drug Saf. 2002;25(5):345–72.PubMedCrossRefGoogle Scholar
  215. 215.
    Stern RS. Photocarcinogenicity of drugs. Toxicol Lett. 1998;102–103:389–92.Google Scholar
  216. 216.
    Stern RS, Bigby M. An expanded profile of cutaneous reactions to nonsteroidal anti-inflammatory drugs. Reports to a specialty-based system for spontaneous reporting of adverse reactions to drugs. JAMA. 1984;252(11):1433–7.PubMedCrossRefGoogle Scholar
  217. 217.
    Sanchez-Borges M, Capriles-Hulett A, Caballero-Fonseca F. Risk of skin reactions when using ibuprofen-based medicines. Expert Opin Drug Saf. 2005;4(5):837–48. doi: 10.1517/14740338.4.5.837.PubMedCrossRefGoogle Scholar
  218. 218.
    Finch LE, Tomiyama AJ. Comfort eating, psychological stress, and depressive symptoms in young adult women. Appetite. 2015;95:239–44. doi: 10.1016/j.appet.2015.07.017.PubMedCrossRefGoogle Scholar
  219. 219.
    Bliss SA, Warnock JK. Psychiatric medications: adverse cutaneous drug reactions. Clin Dermatol. 2013;31(1):101–9. doi: 10.1016/j.clindermatol.2011.11.014.PubMedCrossRefGoogle Scholar
  220. 220.
    Borras L, Huguelet P. A case report of photosensitivity to amisulpride. Prim Care Companion J Clin Psychiatry. 2007;9(2):153.PubMedPubMedCentralCrossRefGoogle Scholar
  221. 221.
    Warnock JK, Morris DW. Adverse cutaneous reactions to antipsychotics. Am J Clin Dermatol. 2002;3(9):629–36.PubMedCrossRefGoogle Scholar
  222. 222.
    Mennella JA, Bobowski NK, Reed DR. The development of sweet taste: from biology to hedonics. Rev Endocr Metab Disord. 2016;17(2):171–8. doi: 10.1007/s11154-016-9360-5.PubMedCrossRefGoogle Scholar
  223. 223.
    Iwasaki JK, Srivastava D, Moy RL, Lin HJ, Kouba DJ. The molecular genetics underlying basal cell carcinoma pathogenesis and links to targeted therapeutics. J Am Acad Dermatol. 2012;66(5):e167–78. doi: 10.1016/j.jaad.2010.06.054.PubMedCrossRefGoogle Scholar
  224. 224.
    Bonilla X, Parmentier L, King B, Bezrukov F, Kaya G, Zoete V, et al. Genomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma. Nat Genet. 2016;48(4):398–406. doi: 10.1038/ng.3525.PubMedCrossRefGoogle Scholar
  225. 225.
    Rogers HW, Weinstock MA, Harris AR, Hinckley MR, Feldman SR, Fleischer AB, et al. Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Arch Dermatol. 2010;146(3):283–7. doi: 10.1001/archdermatol.2010.19.PubMedCrossRefGoogle Scholar
  226. 226.
    Makrantonaki EZC. Molecular mechanisms of skin aging: state of the art. Acad Sci. 2007;1119:40–50.CrossRefGoogle Scholar
  227. 227.
    Yan W, Wistuba II, Emmert-Buck MR, Erickson HS. Squamous cell carcinoma—similarities and differences among anatomical sites. Am J Cancer Res. 2011;1(3):275–300.PubMedCrossRefGoogle Scholar
  228. 228.
    Ibiebele TI, van der Pols JC, Hughes MC, Marks GC, Williams GM, Green AC. Dietary pattern in association with squamous cell carcinoma of the skin: a prospective study. Am J Clin Nutr. 2007;85(5):1401–8.PubMedGoogle Scholar
  229. 229.
    Inoue T, Toda S, Narisawa Y, Sugihara H. Subcutaneous adipocytes promote the differentiation of squamous cell carcinoma cell line (DJM-1) in collagen gel matrix culture. J Invest Dermatol. 2001;117(2):244–50. doi: 10.1046/j.0022-202x.2001.01431.x.PubMedCrossRefGoogle Scholar
  230. 230.
    Rubin AI, Chen EH, Ratner D. Basal-cell carcinoma. N Engl J Med. 2005;353(21):2262–9. doi: 10.1056/NEJMra044151.PubMedCrossRefGoogle Scholar
  231. 231.
    Marzuka AG, Book SE. Basal cell carcinoma: pathogenesis, epidemiology, clinical features, diagnosis, histopathology, and management. Yale J Biol Med. 2015;88(2):167–79.PubMedPubMedCentralGoogle Scholar
  232. 232.
    Espinosa P, Pfeiffer RM, Garcia-Casado Z, Requena C, Landi MT, Kumar R, et al. Risk factors for keratinocyte skin cancer in patients diagnosed with melanoma, a large retrospective study. Eur J Cancer. 2015;53:115–24. doi: 10.1016/j.ejca.2015.10.058.PubMedCrossRefGoogle Scholar
  233. 233.
    Reinau D, Surber C, Jick SS, Meier CR. Epidemiology of basal cell carcinoma in the United Kingdom: incidence, lifestyle factors, and comorbidities. Br J Cancer. 2014;111(1):203–6. doi: 10.1038/bjc.2014.265.PubMedPubMedCentralCrossRefGoogle Scholar
  234. 234.
    Baxter JM, Patel AN, Varma S. Facial basal cell carcinoma. BMJ. 2012;345, e5342. doi: 10.1136/bmj.e5342.PubMedCrossRefGoogle Scholar
  235. 235.
    Cheng P, Weng SD, Chiang CH, Lai FJ. Relationship between arsenic-containing drinking water and skin cancers in the arseniasis endemic areas in Taiwan. J Dermatol. 2016;43(2):181–6.PubMedCrossRefGoogle Scholar
  236. 236.
    Poschl G, Seitz HK. Alcohol and cancer. Alcohol Alcohol. 2004;39(3):155–65.PubMedCrossRefGoogle Scholar
  237. 237.
    Saladi RN, Nektalova T, Fox JL. Induction of skin carcinogenicity by alcohol and ultraviolet light. Clin Exp Dermatol. 2010;35(1):7–11. doi: 10.1111/j.1365-2230.2009.03465.x.PubMedCrossRefGoogle Scholar
  238. 238.
    Song F, Qureshi AA, Gao X, Li T, Han J. Smoking and risk of skin cancer: a prospective analysis and a meta-analysis. Int J Epidemiol. 2012;41(6):1694–705. doi: 10.1093/ije/dys146.PubMedPubMedCentralCrossRefGoogle Scholar
  239. 239.
    Leonardi-Bee J, Ellison T, Bath-Hextall F. Smoking and the risk of nonmelanoma skin cancer: systematic review and meta-analysis. Arch Dermatol. 2012;148(8):939–46. doi: 10.1001/archdermatol.2012.1374.PubMedCrossRefGoogle Scholar
  240. 240.
    Hughes MC, Olsen CM, Williams GM, Green AC. A prospective study of cigarette smoking and basal cell carcinoma. Arch Dermatol Res. 2014;306(9):851–6. doi: 10.1007/s00403-014-1503-5.PubMedCrossRefGoogle Scholar
  241. 241.
    Henderson MT, Kubo JT, Desai M, David SP, Tindle H, Sinha AA, et al. Smoking behavior and association of melanoma and nonmelanoma skin cancer in the Women’s Health Initiative. J Am Acad Dermatol. 2015;72(1):190–1. doi: 10.1016/j.jaad.2014.09.024. e3.PubMedPubMedCentralCrossRefGoogle Scholar
  242. 242.
    Trost SG, Owen N, Bauman AE, Sallis JF, Brown W. Correlates of adults’ participation in physical activity: review and update. Med Sci Sports Exerc. 2002;34(12):1996–2001. doi: 10.1249/01.MSS.0000038974.76900.92.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • K. Karimi
    • 1
  • T. H. Lindgren
    • 1
  • C. A. Koch
    • 2
    • 3
    • 4
  • Robert T. Brodell
    • 5
    • 6
    • 7
  1. 1.School of MedicineTexas Tech University Health Sciences CenterLubbockUSA
  2. 2.Division of EndocrinologyUniversity of Mississippi Medical CenterJacksonUSA
  3. 3.Cancer InstituteUniversity of Mississippi Medical CenterJacksonUSA
  4. 4.G.V. (Sonny) Montgomery VA Medical CenterJacksonUSA
  5. 5.Department of DermatologyUniversity of Mississippi Medical CenterJacksonUSA
  6. 6.Department of PathologyUniversity of Mississippi Medical CenterJacksonUSA
  7. 7.Department of DermatologyUniversity of Rochester School of Medicine and DentistryRochesterUSA

Personalised recommendations