Birth Weight and Cancer Associations

  • Nadia BarahmaniEmail author
  • M. Fatih Okcu


Birth weight is an established risk factor for development of childhood acute lymphoblastic leukemia (ALL); however, the biological mechanism of this correlation is unknown. Some possible mechanisms of birth weight association in childhood cancer are increased cell proliferation rate; the combination of high IGF and low IGFBP levels; maternal estrogen level; and higher iron (nutrient for cancer cells) levels in heavier babies. Birth weight increases with gestational age; therefore it is important to adjust birth weight for gestational age or use percentile of weight for gestational age or fetal growth rate in birth weight related studies. Further studies are still needed to explore biological reasons of confounder of the association between birth weight and cancer, so ultimately, preventive and therapeutic interventions can be initiated.


Birth weight Gestational age or fetal growth rate IGF IGFBP Maternal estrogen Iron Childhood cancer 


  1. Abbas, S., Linseisen, J., Slanger, T., Kropp, S., Mutschelknauss, E.J., Flesch-Janys, D., Chang-Claude, J., 2008. The Gc2 allele of the vitamin D binding protein is associated with a decreased postmenopausal breast cancer risk, independent of the vitamin D status. Cancer Epidemiol Biomarkers Prev 17, 1339–1343.PubMedCrossRefGoogle Scholar
  2. Agarwal, K.N., Agarwal, D.K., Mishra, K.P., 1991. Impact of anaemia prophylaxis in pregnancy on maternal haemoglobin, serum ferritin & birth weight. Indian J Med Res 94, 277–280.PubMedGoogle Scholar
  3. Ahlgren, M., Wohlfahrt, J., Olsen, L.W., Sorensen, T.I., Melbye, M., 2007. Birth weight and risk of cancer. Cancer 110, 412–419.PubMedCrossRefGoogle Scholar
  4. Ahlsson, F., Gustafsson, J., Tuvemo, T., Lundgren, M., 2007. Females born large for gestational age have a doubled risk of giving birth to large for gestational age infants. Acta Paediatr 96, 358–362.PubMedCrossRefGoogle Scholar
  5. Albanes, D., Winick, M., 1988. Are cell number and cell proliferation risk factors for cancer? J Natl Cancer Inst 80, 772–774.PubMedCrossRefGoogle Scholar
  6. Allen, L.H., 2000. Anemia and iron deficiency: effects on pregnancy outcome. Am J Clin Nutr 71, 1280S–1284S.PubMedGoogle Scholar
  7. Al-Zahrani, A., Sandhu, M.S., Luben, R.N., Thompson, D., Baynes, C., Pooley, K.A., Luccarini, C., Munday, H., Perkins, B., Smith, P., Pharoah, P.D., Wareham, N.J., Easton, D.F., Ponder, B.A., Dunning, A.M., 2006. IGF1 and IGFBP3 tagging polymorphisms are associated with circulating levels of IGF1, IGFBP3 and risk of breast cancer. Hum Mol Genet 15, 1–10.PubMedCrossRefGoogle Scholar
  8. Amante, A., Gloria-Bottini, F., Bottini, E., 1990. Intrauterine growth: association with acid phosphatase genetic polymorphism. J Perinat Med 18, 275–282.PubMedCrossRefGoogle Scholar
  9. Arya, R., Demerath, E., Jenkinson, C.P., Goring, H.H., Puppala, S., Farook, V., Fowler, S., Schneider, J., Granato, R., Resendez, R.G., Dyer, T.D., Cole, S.A., Almasy, L., Comuzzie, A.G., Siervogel, R.M., Bradshaw, B., Defronzo, R.A., Maccluer, J., Stern, M.P., Towne, B., Blangero, J., Duggirala, R., 2006. A quantitative trait locus (QTL) on chromosome 6q influences birth weight in two independent family studies. Hum Mol Genet 15, 1569–1579.PubMedCrossRefGoogle Scholar
  10. Ashley, D.J., 1969. A male-female differential in tumour incidence. Br J Cancer 23, 21–25.PubMedCrossRefGoogle Scholar
  11. Baik, I., Devito, W.J., Ballen, K., Becker, P.S., Okulicz, W., Liu, Q., Delpapa, E., Lagiou, P., Sturgeon, S., Trichopoulos, D., Quesenberry, P.J., Hsieh, C.C., 2005. Association of fetal hormone levels with stem cell potential: evidence for early life roots of human cancer. Cancer Res 65, 358–363.PubMedGoogle Scholar
  12. Baker, J., Liu, J.P., Robertson, E.J., Efstratiadis, A., 1993. Role of insulin-like growth factors in embryonic and postnatal growth. Cell 75, 73–82.PubMedGoogle Scholar
  13. Basso, O., Wilcox, A.J., Weinberg, C.R., 2006. Birth weight and mortality: causality or confounding? Am J Epidemiol 164, 303–311.PubMedCrossRefGoogle Scholar
  14. Boulet, S.L., Alexander, G.R., Salihu, H.M., Pass, M., 2003. Macrosomic births in the United States: determinants, outcomes, and proposed grades of risk. Am J Obstet Gynecol 188, 1372–1378.PubMedCrossRefGoogle Scholar
  15. Boyne, M.S., Thame, M., Bennett, F.I., Osmond, C., Miell, J.P., Forrester, T.E., 2003. The relationship among circulating insulin-like growth factor (IGF)-I, IGF-binding proteins-1 and -2, and birth anthropometry: a prospective study. J Clin Endocrinol Metab 88, 1687–1691.PubMedCrossRefGoogle Scholar
  16. Busch, C.P., Ramdath, D.D., Ramsewak, S., Hegele, R.A., 1999. Association of PON2 variation with birth weight in Trinidadian neonates of South Asian ancestry. Pharmacogenetics 9, 351–356.PubMedCrossRefGoogle Scholar
  17. Callan, A.C., Milne, E., 2009. Involvement of the IGF system in fetal growth and childhood cancer: an overview of potential mechanisms. Cancer Causes Control 20(10), 1783–1798.PubMedCrossRefGoogle Scholar
  18. Cartwright, R.A., Gurney, K.A., Moorman, A.V., 2002. Sex ratios and the risks of haematological malignancies. Br J Haematol 118, 1071–1077.PubMedCrossRefGoogle Scholar
  19. Caughey, R.W., Michels, K.B., 2009. Birth weight and childhood leukemia: A meta-analysis and review of the current evidence. Int J Cancer 124, 2658–2670.PubMedCrossRefGoogle Scholar
  20. Cazzola, M., Bergamaschi, G., Dezza, L., Arosio, P., 1990. Manipulations of cellular iron metabolism for modulating normal and malignant cell proliferation: achievements and prospects. Blood 75, 1903–1919.PubMedGoogle Scholar
  21. Cogswell, M.E., Parvanta, I., Ickes, L., Yip, R., Brittenham, G.M., 2003. Iron supplementation during pregnancy, anemia, and birth weight: a randomized controlled trial. Am J Clin Nutr 78, 773–781.PubMedGoogle Scholar
  22. Comiskey, M., Goldstein, C.Y., De Fazio, S.R., Mammolenti, M., Newmark, J.A., Warner, C.M., 2003. Evidence that HLA-G is the functional homolog of mouse Qa-2, the Ped gene product. Hum Immunol 64, 999–1004.PubMedCrossRefGoogle Scholar
  23. Daling, J.R., Starzyk, P., Olshan, A.F., Weiss, N.S., 1984. Birth weight and the incidence of childhood cancer. J Natl Cancer Inst 72, 1039–1041.PubMedGoogle Scholar
  24. Datz, C., Haas, T., Rinner, H., Sandhofer, F., Patsch, W., Paulweber, B., 1998. Heterozygosity for the C282Y mutation in the hemochromatosis gene is associated with increased serum iron, transferrin saturation, and hemoglobin in young women: a protective role against iron deficiency? Clin Chem 44, 2429–2432.PubMedGoogle Scholar
  25. Dina, C., Meyre, D., Gallina, S., Durand, E., Korner, A., Jacobson, P., Carlsson, L.M., Kiess, W., Vatin, V., Lecoeur, C., Delplanque, J., Vaillant, E., Pattou, F., Ruiz, J., Weill, J., Levy-Marchal, C., Horber, F., Potoczna, N., Hercberg, S., Le Stunff, C., Bougneres, P., Kovacs, P., Marre, M., Balkau, B., Cauchi, S., Chevre, J.C., Froguel, P., 2007. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet 39, 724–726.PubMedCrossRefGoogle Scholar
  26. Diorio, C., Brisson, J., Berube, S., Pollak, M., 2008. Genetic polymorphisms involved in insulin-like growth factor (IGF) pathway in relation to mammographic breast density and IGF levels. Cancer Epidemiol Biomarkers Prev 17, 880–888.PubMedCrossRefGoogle Scholar
  27. Dissanayake, V.H., Tower, C., Broderick, A., Stocker, L.J., Seneviratne, H.R., Jayasekara, R.W., Kalsheker, N., Broughton Pipkin, F., Morgan, L., 2007. Polymorphism in the epidermal growth factor gene is associated with birthweight in Sinhalese and white Western Europeans. Mol Hum Reprod 13, 425–429.PubMedCrossRefGoogle Scholar
  28. Dorak, M.T., 2006. HFE H63D variant and leukemia susceptibility. Leuk Lymphoma 47, 2269–2270.PubMedCrossRefGoogle Scholar
  29. Dorak, M.T., Burnett, A.K., Worwood, M., 2005. HFE gene mutations in susceptibility to childhood leukemia: HuGE review. Genet Med 7, 159–168.PubMedCrossRefGoogle Scholar
  30. Dorak, M.T., Hammal, D.M., Pearce, M.S., McNally, R.J., Parker, L., 2007. Examination of gender effect in birth weight and miscarriage associations with childhood cancer. Cancer Causes Control 18, 219–228.PubMedCrossRefGoogle Scholar
  31. Dorak, M.T., Mackay, R.K., Relton, C.L., Worwood, M., Parker, L., Hall, A.G., 2009. Hereditary hemochromatosis gene (HFE) variants are associated with birth weight and childhood leukemia risk. Pediatr Blood Cancer 53, 1242–1248.Google Scholar
  32. Dorak, M.T., Sproul, A.M., Gibson, B.E., Burnett, A.K., Worwood, M., 1999. The C282Y mutation of HFE is another male-specific risk factor for childhood ALL. Blood 94, 3957–3958.PubMedGoogle Scholar
  33. Dunger, D.B., Ong, K.K., Huxtable, S.J., Sherriff, A., Woods, K.A., Ahmed, M.L., Golding, J., Pembrey, M.E., Ring, S., Bennett, S.T., Todd, J.A., 1998. Association of the INS VNTR with size at birth. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. Nat Genet 19, 98–100.PubMedCrossRefGoogle Scholar
  34. Dunger, D.B., Petry, C.J., Ong, K.K., 2007. Genetics of size at birth. Diabetes Care 30 Suppl 2,S150–S155.PubMedCrossRefGoogle Scholar
  35. Engelman, C.D., Fingerlin, T.E., Langefeld, C.D., Hicks, P.J., Rich, S.S., Wagenknecht, L.E., Bowden, D.W., Norris, J.M., 2008. Genetic and environmental determinants of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels in Hispanic and African Americans. J Clin Endocrinol Metab 93, 3381–3388.PubMedCrossRefGoogle Scholar
  36. Eriksson, M., Wedel, H., Wallander, M.A., Krakau, I., Hugosson, J., Carlsson, S., Svardsudd, K., 2007. The impact of birth weight on prostate cancer incidence and mortality in a population-based study of men born in 1913 and followed up from 50 to 85 years of age. Prostate 67, 1247–1254.PubMedCrossRefGoogle Scholar
  37. Esterbauer, H., Schneitler, C., Oberkofler, H., Ebenbichler, C., Paulweber, B., Sandhofer, F., Ladurner, G., Hell, E., Strosberg, A.D., Patsch, J.R., Krempler, F., Patsch, W., 2001. A common polymorphism in the promoter of UCP2 is associated with decreased risk of obesity in middle-aged humans. Nat Genet 28, 178–183.PubMedCrossRefGoogle Scholar
  38. Fosset, C., McGaw, B.A., Abramovich, D., McArdle, H.J., 2004. Interrelations between ceruloplasmin and Fe status during human pregnancy. Biol Trace Elem Res 98, 1–12.PubMedCrossRefGoogle Scholar
  39. Fradin, D., Bougneres, P., 2007. Three common intronic variants in the maternal and fetal thiamine pyrophosphokinase gene (TPK1) are associated with birth weight. Ann Hum Genet 71, 578–585.PubMedCrossRefGoogle Scholar
  40. Fradin, D., Heath, S., Lepercq, J., Lathrop, M., Bougneres, P., 2006. Identification of distinct quantitative trait loci affecting length or weight variability at birth in humans. J Clin Endocrinol Metab 91, 4164–4170.PubMedCrossRefGoogle Scholar
  41. Frayling, T.M., Timpson, N.J., Weedon, M.N., Zeggini, E., Freathy, R.M., Lindgren, C.M., Perry, J.R., Elliott, K.S., Lango, H., Rayner, N.W., Shields, B., Harries, L.W., Barrett, J.C., Ellard, S., Groves, C.J., Knight, B., Patch, A.M., Ness, A.R., Ebrahim, S., Lawlor, D.A., Ring, S.M., Ben-Shlomo, Y., Jarvelin, M.R., Sovio, U., Bennett, A.J., Melzer, D., Ferrucci, L., Loos, R.J., Barroso, I., Wareham, N.J., Karpe, F., Owen, K.R., Cardon, L.R., Walker, M., Hitman, G.A., Palmer, C.N., Doney, A.S., Morris, A.D., Smith, G.D., Hattersley, A.T., McCarthy, M.I., 2007. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316, 889–894.PubMedCrossRefGoogle Scholar
  42. Freathy, R.M., Bennett, A.J., Ring, S.M., Shields, B., Groves, C.J., Timpson, N.J., Weedon, M.N., Zeggini, E., Lindgren, C.M., Lango, H., Perry, J.R., Pouta, A., Ruokonen, A., Hypponen, E., Power, C., Elliott, P., Strachan, D.P., Jarvelin, M.R., Smith, G.D., McCarthy, M.I., Frayling, T.M., Hattersley, A.T., 2009. Type 2 diabetes risk alleles are associated with reduced size at birth. Diabetes 58, 1428–1433.PubMedCrossRefGoogle Scholar
  43. Freathy, R.M., Weedon, M.N., Bennett, A., Hypponen, E., Relton, C.L., Knight, B., Shields, B., Parnell, K.S., Groves, C.J., Ring, S.M., Pembrey, M.E., Ben-Shlomo, Y., Strachan, D.P., Power, C., Jarvelin, M.R., McCarthy, M.I., Davey Smith, G., Hattersley, A.T., Frayling, T.M., 2007. Type 2 diabetes TCF7L2 risk genotypes alter birth weight: a study of 24,053 individuals. Am J Hum Genet 80, 1150–1161.PubMedCrossRefGoogle Scholar
  44. Gambling, L., McArdle, H.J., 2004. Iron, copper and fetal development. Proc Nutr Soc 63, 553–562.PubMedCrossRefGoogle Scholar
  45. Gloria-Bottini, F., Lucarini, N., La Torre, M., Lucarelli, P., Bottini, E., 2001. Birth weight and parental PGM1 alleles. Am J Hum Biol 13, 417–420.PubMedCrossRefGoogle Scholar
  46. Gloria-Bottini, F., Pietropolli, A., Coppeta, L., Magrini, A., Bergamaschi, A., Bottini, E., 2008. The genetics of feto-placental development: a study of acid phosphatase locus 1 and adenosine deaminase polymorphisms in a consecutive series of newborn infants. Reprod Biol Endocrinol 6, 38.PubMedCrossRefGoogle Scholar
  47. Godfrey, K.M., 2001. The ‘gold standard’ for optimal fetal growth and development. J Pediatr Endocrinol Metab 14 Suppl 6,1507–1513.PubMedGoogle Scholar
  48. Haram, K., Nilsen, S.T., Ulvik, R.J., 2001. Iron supplementation in pregnancy–evidence and controversies. Acta Obstet Gynecol Scand 80, 683–688.PubMedCrossRefGoogle Scholar
  49. Harder, T., Plagemann, A., Harder, A., 2008. Birth weight and subsequent risk of childhood primary brain tumors: a meta-analysis. Am J Epidemiol 168, 366–373.PubMedCrossRefGoogle Scholar
  50. Hattersley, A.T., Beards, F., Ballantyne, E., Appleton, M., Harvey, R., Ellard, S., 1998. Mutations in the glucokinase gene of the fetus result in reduced birth weight. Nat Genet 19, 268–270.PubMedCrossRefGoogle Scholar
  51. Heiskanen, N., Raatikainen, K., Heinonen, S., 2006. Fetal macrosomia–a continuing obstetric challenge. Biol Neonate 90, 98–103.PubMedCrossRefGoogle Scholar
  52. Herbert, A., Gerry, N.P., McQueen, M.B., Heid, I.M., Pfeufer, A., Illig, T., Wichmann, H.E., Meitinger, T., Hunter, D., Hu, F.B., Colditz, G., Hinney, A., Hebebrand, J., Koberwitz, K., Zhu, X., Cooper, R., Ardlie, K., Lyon, H., Hirschhorn, J.N., Laird, N.M., Lenburg, M.E., Lange, C., Christman, M.F., 2006. A common genetic variant is associated with adult and childhood obesity. Science 312, 279–283.PubMedCrossRefGoogle Scholar
  53. Hjalgrim, L.L., Westergaard, T., Rostgaard, K., Schmiegelow, K., Melbye, M., Hjalgrim, H., Engels, E.A., 2003. Birth weight as a risk factor for childhood leukemia: a meta-analysis of 18 epidemiologic studies. Am J Epidemiol 158, 724–735.PubMedCrossRefGoogle Scholar
  54. Hoffstedt, J., Eriksson, P., Mottagui-Tabar, S., Arner, P., 2002. A polymorphism in the leptin promoter region (-2548 G/A) influences gene expression and adipose tissue secretion of leptin. Horm Metab Res 34, 355–359.PubMedCrossRefGoogle Scholar
  55. Hofker, M., Wijmenga, C., 2009. A supersized list of obesity genes. Nat Genet 41, 139–140.PubMedCrossRefGoogle Scholar
  56. Hudson, G., 1965. Bone-marrow volume in the human foetus and newborn. Br J Haematol 11, 446–452.PubMedCrossRefGoogle Scholar
  57. Hviid, T.V., 2004. HLA-G genotype is associated with fetoplacental growth. Hum Immunol 65, 586–593.PubMedCrossRefGoogle Scholar
  58. Jiang, Y., Wilk, J.B., Borecki, I., Williamson, S., DeStefano, A.L., Xu, G., Liu, J., Ellison, R.C., Province, M., Myers, R.H., 2004. Common variants in the 5 region of the leptin gene are associated with body mass index in men from the National Heart, Lung, and Blood Institute Family Heart Study. Am J Hum Genet 75, 220–230.PubMedCrossRefGoogle Scholar
  59. Jiang, H., Xiong, D.H., Guo, Y.F., Shen, H., Xiao, P., Yang, F., Chen, Y., Zhang, F., Recker, R.R., Deng, H.W., 2007. Association analysis of vitamin D-binding protein gene polymorphisms with variations of obesity-related traits in Caucasian nuclear families. Int J Obes (Lond) 31, 1319–1324.CrossRefGoogle Scholar
  60. Kaye, S.A., Robison, L.L., Smithson, W.A., Gunderson, P., King, F.L., Neglia, J.P., 1991. Maternal reproductive history and birth characteristics in childhood acute lymphoblastic leukemia. Cancer 68, 1351–1355.PubMedCrossRefGoogle Scholar
  61. Kochhar, H.P., Peippo, J., King, W.A., 2001. Sex related embryo development. Theriogenology 55, 3–14.PubMedCrossRefGoogle Scholar
  62. Kramer, M.S., Morin, I., Yang, H., Platt, R.W., Usher, R., McNamara, H., Joseph, K.S., Wen, S.W., 2002. Why are babies getting bigger? Temporal trends in fetal growth and its determinants. J Pediatr 141, 538–542.PubMedCrossRefGoogle Scholar
  63. Laurvick, C.L., Milne, E., Blair, E., de Klerk, N., Charles, A.K., Bower, C., 2008. Fetal growth and the risk of childhood non-CNS solid tumours in Western Australia. Br J Cancer 99, 179–181.PubMedCrossRefGoogle Scholar
  64. Le, N.T., Richardson, D.R., 2002. The role of iron in cell cycle progression and the proliferation of neoplastic cells. Biochim Biophys Acta 1603, 31–46.PubMedGoogle Scholar
  65. Linet, M.S., Wacholder, S., Zahm, S.H., 2003. Interpreting epidemiologic research: lessons from studies of childhood cancer. Pediatrics 112, 218–232.PubMedGoogle Scholar
  66. McCormack, V.A., dos Santos Silva, I., Koupil, I., Leon, D.A., Lithell, H.O., 2005. Birth characteristics and adult cancer incidence: Swedish cohort of over 11,000 men and women. Int J Cancer 115, 611–617.PubMedCrossRefGoogle Scholar
  67. Meis, P.J., Michielutte, R., Peters, T.J., Wells, H.B., Sands, R.E., Coles, E.C., Johns, K.A., 1997. Factors associated with term low birthweight in Cardiff, Wales. Paediatr Perinat Epidemiol 11, 287–297.PubMedCrossRefGoogle Scholar
  68. Melve, K.K., Skjaerven, R., 2003. Birthweight and perinatal mortality: paradoxes, social class, and sibling dependencies. Int J Epidemiol 32, 625–632.PubMedCrossRefGoogle Scholar
  69. Meyre, D., Delplanque, J., Chevre, J.C., Lecoeur, C., Lobbens, S., Gallina, S., Durand, E., Vatin, V., Degraeve, F., Proenca, C., Gaget, S., Korner, A., Kovacs, P., Kiess, W., Tichet, J., Marre, M., Hartikainen, A.L., Horber, F., Potoczna, N., Hercberg, S., Levy-Marchal, C., Pattou, F., Heude, B., Tauber, M., McCarthy, M.I., Blakemore, A.I., Montpetit, A., Polychronakos, C., Weill, J., Coin, L.J., Asher, J., Elliott, P., Jarvelin, M.R., Visvikis-Siest, S., Balkau, B., Sladek, R., Balding, D., Walley, A., Dina, C., Froguel, P., 2009. Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nat Genet 41, 157–159.PubMedCrossRefGoogle Scholar
  70. Michos, A., Xue, F., Michels, K.B., 2007. Birth weight and the risk of testicular cancer: a meta-analysis. Int J Cancer 121, 1123–1131.PubMedCrossRefGoogle Scholar
  71. Milman, N., 2006. Iron prophylaxis in pregnancy–general or individual and in which dose? Ann Hematol 85, 821–828.PubMedCrossRefGoogle Scholar
  72. Milne, E., Laurvick, C.L., Blair, E., Bower, C., de Klerk, N., 2007. Fetal growth and acute childhood leukemia: looking beyond birth weight. Am J Epidemiol 166, 151–159.PubMedCrossRefGoogle Scholar
  73. Milne, E., Laurvick, C.L., Blair, E., de Klerk, N., Charles, A.K., Bower, C., 2008. Fetal growth and the risk of childhood CNS tumors and lymphomas in Western Australia. Int J Cancer 123, 436–443.PubMedCrossRefGoogle Scholar
  74. Milne, E., Royle, J.A., de Klerk, N.H., Blair, E., Bailey, H., Cole, C., Attia, J., Scott, R.J., Armstrong, B.K., 2009. Fetal growth and risk of childhood acute lymphoblastic leukemia: results from an Australian case-control study. Am J Epidemiol 170, 221–228.PubMedCrossRefGoogle Scholar
  75. Mitchell, E.A., Robinson, E., Clark, P.M., Becroft, D.M., Glavish, N., Pattison, N.S., Pryor, J.E., Thompson, J.M., Wild, C.J., 2004. Maternal nutritional risk factors for small for gestational age babies in a developed country: a case-control study. Arch Dis Child Fetal Neonatal Ed 89, F431–F435.PubMedCrossRefGoogle Scholar
  76. Mittwoch, U., 1993. Blastocysts prepare for the race to be male. Hum Reprod 8, 1550–1555.PubMedGoogle Scholar
  77. Moschos, S.J., Mantzoros, C.S., 2002. The role of the IGF system in cancer: from basic to clinical studies and clinical applications. Oncology 63, 317–332.PubMedCrossRefGoogle Scholar
  78. Nilsen, T.I., Romundstad, P.R., Troisi, R., Potischman, N., Vatten, L.J., 2005a. Birth size and colorectal cancer risk: a prospective population based study. Gut 54, 1728–1732.PubMedCrossRefGoogle Scholar
  79. Nilsen, T.I., Romundstad, P.R., Troisi, R., Vatten, L.J., 2005b. Birth size and subsequent risk for prostate cancer: a prospective population-based study in Norway. Int J Cancer 113, 1002–1004.PubMedCrossRefGoogle Scholar
  80. Okcu, M.F., Goodman, K.J., Carozza, S.E., Weiss, N.S., Burau, K.D., Bleyer, W.A., Cooper, S.P., 2002. Birth weight, ethnicity, and occurrence of cancer in children: a population-based, incident case-control study in the State of Texas, USA. Cancer Causes Control 13, 595–602.PubMedCrossRefGoogle Scholar
  81. Ong, K.K., Ahmed, M.L., Sherriff, A., Woods, K.A., Watts, A., Golding, J., Dunger, D.B., 1999. Cord blood leptin is associated with size at birth and predicts infancy weight gain in humans. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. J Clin Endocrinol Metab 84, 1145–1148.PubMedCrossRefGoogle Scholar
  82. Ouban, A., Muraca, P., Yeatman, T., Coppola, D., 2003. Expression and distribution of insulin-like growth factor-1 receptor in human carcinomas. Hum Pathol 34, 803–808.PubMedCrossRefGoogle Scholar
  83. Palma, S., Perez-Iglesias, R., Prieto, D., Pardo, R., Llorca, J., Delgado-Rodriguez, M., 2008. Iron but not folic acid supplementation reduces the risk of low birthweight in pregnant women without anaemia: a case-control study. J Epidemiol Community Health 62, 120–124.PubMedCrossRefGoogle Scholar
  84. Park, S.K., Kang, D., McGlynn, K.A., Garcia-Closas, M., Kim, Y., Yoo, K.Y., Brinton, L.A., 2008. Intrauterine environments and breast cancer risk: meta-analysis and systematic review. Breast Cancer Res 10, R8.PubMedCrossRefGoogle Scholar
  85. Pearce, M.S., Parker, L., 2001. Childhood cancer registrations in the developing world: still more boys than girls. Int J Cancer 91, 402–406.PubMedCrossRefGoogle Scholar
  86. Peck, J.D., Hulka, B.S., Savitz, D.A., Baird, D., Poole, C., Richardson, B.E., 2003. Accuracy of fetal growth indicators as surrogate measures of steroid hormone levels during pregnancy. Am J Epidemiol 157, 258–266.PubMedCrossRefGoogle Scholar
  87. Peters, T.J., Golding, J., Butler, N.R., Fryer, J.G., Lawrence, C.J., Chamberlain, G.V., 1983. Plus ca change: predictors of birthweight in two national studies. Br J Obstet Gynaecol 90, 1040–1045.PubMedCrossRefGoogle Scholar
  88. Petridou, E.T., Dikalioti, S.K., Skalkidou, A., Andrie, E., Dessypris, N., Trichopoulos, D., 2007. Sun exposure, birth weight, and childhood lymphomas: a case control study in Greece. Cancer Causes Control 18, 1031–1037.PubMedCrossRefGoogle Scholar
  89. Petridou, E., Panagiotopoulou, K., Katsouyanni, K., Spanos, E., Trichopoulos, D., 1990. Tobacco smoking, pregnancy estrogens, and birth weight. Epidemiology 1, 247–250.PubMedCrossRefGoogle Scholar
  90. Petridou, E., Skalkidou, A., Dessypris, N., Moustaki, M., Mantzoros, C., Spanos, E., Trichopoulos, D., 2000. Endogenous risk factors for childhood leukemia in relation to the IGF system (Greece). The Childhood Haematologists-Oncologists Group. Cancer Causes Control 11, 765–771.PubMedCrossRefGoogle Scholar
  91. Petry, C.J., Ong, K.K., Barratt, B.J., Wingate, D., Cordell, H.J., Ring, S.M., Pembrey, M.E., Reik, W., Todd, J.A., Dunger, D.B., 2005. Common polymorphism in H19 associated with birthweight and cord blood IGF-II levels in humans. BMC Genet 6, 22.PubMedCrossRefGoogle Scholar
  92. Pfab, T., Poralla, C., Richter, C.M., Godes, M., Slowinski, T., Priem, F., Halle, H., Hocher, B., 2006. Fetal and maternal peroxisome proliferator-activated receptor gamma2 Pro12Ala does not influence birth weight. Obesity (Silver Spring) 14, 1880–1885.CrossRefGoogle Scholar
  93. Pihlajamaki, J., Vanhala, M., Vanhala, P., Laakso, M., 2004. The Pro12Ala polymorphism of the PPAR gamma 2 gene regulates weight from birth to adulthood. Obes Res 12, 187–190.PubMedCrossRefGoogle Scholar
  94. Preston-Martin, S., Pike, M.C., Ross, R.K., Jones, P.A., Henderson, B.E., 1990. Increased cell division as a cause of human cancer. Cancer Res 50, 7415–7421.PubMedGoogle Scholar
  95. Relton, C.L., Pearce, M.S., Burn, J., Parker, L., 2005. An investigation of folate-related genetic factors in the determination of birthweight. Paediatr Perinat Epidemiol 19, 360–367.PubMedCrossRefGoogle Scholar
  96. Renehan, A.G., Zwahlen, M., Minder, C., O’Dwyer, S.T., Shalet, S.M., Egger, M., 2004. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 363, 1346–1353.PubMedCrossRefGoogle Scholar
  97. Ricart, W., Lopez, J., Mozas, J., Pericot, A., Sancho, M.A., Gonzalez, N., Balsells, M., Luna, R., Cortazar, A., Navarro, P., Ramirez, O., Flandez, B., Pallardo, L.F., Hernandez-Mijas, A., Ampudia, J., Fernandez-Real, J.M., Corcoy, R., 2005. Body mass index has a greater impact on pregnancy outcomes than gestational hyperglycaemia. Diabetologia 48, 1736–1742.PubMedCrossRefGoogle Scholar
  98. Robison, L.L., Codd, M., Gunderson, P., Neglia, J.P., Smithson, W.A., King, F.L., 1987. Birth weight as a risk factor for childhood acute lymphoblastic leukemia. Pediatr Hematol Oncol 4, 63–72.PubMedCrossRefGoogle Scholar
  99. Ross, J.A., 2006. High birthweight and cancer: evidence and implications. Cancer Epidemiol Biomarkers Prev 15, 1–2.PubMedCrossRefGoogle Scholar
  100. Ross, J.A., Perentesis, J.P., Robison, L.L., Davies, S.M., 1996. Big babies and infant leukemia: a role for insulin-like growth factor-1? Cancer Causes Control 7, 553–559.PubMedCrossRefGoogle Scholar
  101. Ross, J.A., Potter, J.D., Shu, X.O., Reaman, G.H., Lampkin, B., Robison, L.L., 1997. Evaluating the relationships among maternal reproductive history, birth characteristics, and infant leukemia: a report from the Children’s Cancer Group. Ann Epidemiol 7, 172–179.PubMedCrossRefGoogle Scholar
  102. Scholl, T.O., 2005. Iro n status during pregnancy: setting the stage for mother and infant. Am J Clin Nutr 81, 1218S–1222S.PubMedGoogle Scholar
  103. Scholl, T.O., Hediger, M.L., 1994. Anemia and iron-deficiency anemia: compilation of data on pregnancy outcome. Am J Clin Nutr 59, 492S–500S discussion 500S–501S.PubMedGoogle Scholar
  104. Schuz, J., Forman, M.R., 2007. Birthweight by gestational age and childhood cancer. Cancer Causes Control 18, 655–663.PubMedCrossRefGoogle Scholar
  105. Shu, X.O., Han, D., Severson, R.K., Chen, Z., Neglia, J.P., Reaman, G.H., Buckley, J.D., Robison, L.L., 2002. Birth characteristics, maternal reproductive history, hormone use during pregnancy, and risk of childhood acute lymphocytic leukemia by immunophenotype (United States). Cancer Causes Control 13, 15–25.CrossRefGoogle Scholar
  106. Siega-Riz, A.M., Hartzema, A.G., Turnbull, C., Thorp, J., McDonald, T., Cogswell, M.E., 2006. The effects of prophylactic iron given in prenatal supplements on iron status and birth outcomes: a randomized controlled trial. Am J Obstet Gynecol 194, 512–519.PubMedCrossRefGoogle Scholar
  107. Silva Idos, S., De Stavola, B., McCormack, V., 2008. Birth size and breast cancer risk: re-analysis of individual participant data from 32 studies. PLoS Med 5, e193.PubMedCrossRefGoogle Scholar
  108. Simmons, R., 2005. Developmental origins of adult metabolic disease: concepts and controversies. Trends Endocrinol Metab 16, 390–394.PubMedCrossRefGoogle Scholar
  109. Sinotte, M., Diorio, C., Berube, S., Pollak, M., Brisson, J., 2009. Genetic polymorphisms of the vitamin D binding protein and plasma concentrations of 25-hydroxyvitamin D in premenopausal women. Am J Clin Nutr 89, 634–640.PubMedCrossRefGoogle Scholar
  110. Skalkidou, A., Petridou, E., Papathoma, E., Salvanos, H., Kedikoglou, S., Chrousos, G., Trichopoulos, D., 2003. Determinants and consequences of major insulin-like growth factor components among full-term healthy neonates. Cancer Epidemiol Biomarkers Prev 12, 860–865.PubMedGoogle Scholar
  111. Sprehe, M.R., Barahmani, N., Cao, Y., Wang, T., Forman, M.R., Bondy, M., Okcu, M.F., 2009. Comparison of birth weight corrected for gestational age and birth weight alone in prediction of development of childhood leukemia and central nervous system tumors. Pediatr Blood Cancer 54 2, 242–249.Google Scholar
  112. Srivastava, S., Mehrotra, P.K., Srivastava, S.P., Siddiqui, M.K., 2002. Some essential elements in maternal and cord blood in relation to birth weight and gestational age of the baby. Biol Trace Elem Res 86, 97–105.PubMedCrossRefGoogle Scholar
  113. Stevens, R.G., Graubard, B.I., Micozzi, M.S., Neriishi, K., Blumberg, B.S., 1994. Moderate elevation of body iron level and increased risk of cancer occurrence and death. Int J Cancer 56, 364–369.PubMedCrossRefGoogle Scholar
  114. Stevens, R.G., Jones, D.Y., Micozzi, M.S., Taylor, P.R., 1988. Body iron stores and the risk of cancer. N Engl J Med 319, 1047–1052.PubMedCrossRefGoogle Scholar
  115. Storms, M.R., Van Howe, R.S., 2004. Birthweight by gestational age and sex at a rural referral center. J Perinatol 24, 236–240.PubMedCrossRefGoogle Scholar
  116. Surkan, P.J., Hsieh, C.C., Johansson, A.L., Dickman, P.W., Cnattingius, S., 2004. Reasons for increasing trends in large for gestational age births. Obstet Gynecol 104, 720–726.PubMedCrossRefGoogle Scholar
  117. Thorleifsson, G., Walters, G.B., Gudbjartsson, D.F., Steinthorsdottir, V., Sulem, P., Helgadottir, A., Styrkarsdottir, U., Gretarsdottir, S., Thorlacius, S., Jonsdottir, I., Jonsdottir, T., Olafsdottir, E.J., Olafsdottir, G.H., Jonsson, T., Jonsson, F., Borch-Johnsen, K., Hansen, T., Andersen, G., Jorgensen, T., Lauritzen, T., Aben, K.K., Verbeek, A.L., Roeleveld, N., Kampman, E., Yanek, L.R., Becker, L.C., Tryggvadottir, L., Rafnar, T., Becker, D.M., Gulcher, J., Kiemeney, L.A., Pedersen, O., Kong, A., Thorsteinsdottir, U., Stefansson, K., 2009. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet 41, 18–24.PubMedCrossRefGoogle Scholar
  118. Tower, R.L., Spector, L.G., 2007. The epidemiology of childhood leukemia with a focus on birth weight and diet. Crit Rev Clin Lab Sci 44, 203–242.PubMedCrossRefGoogle Scholar
  119. Trowbridge, I.S., Domingo, D.L., 1981. Anti-transferrin receptor monoclonal antibody and toxin-antibody conjugates affect growth of human tumour cells. Nature 294, 171–173.PubMedCrossRefGoogle Scholar
  120. Trowbridge, I.S., Lopez, F., 1982. Monoclonal antibody to transferrin receptor blocks transferrin binding and inhibits human tumor cell growth in vitro. Proc Natl Acad Sci U S A 79, 1175–1179.PubMedCrossRefGoogle Scholar
  121. Vaclavicek, A., Hemminki, K., Bartram, C.R., Wagner, K., Wappenschmidt, B., Meindl, A., Schmutzler, R.K., Klaes, R., Untch, M., Burwinkel, B., Forsti, A., 2006. Association of prolactin and its receptor gene regions with familial breast cancer. J Clin Endocrinol Metab 91, 1513–1519.PubMedCrossRefGoogle Scholar
  122. Vella, A., Bouatia-Naji, N., Heude, B., Cooper, J.D., Lowe, C.E., Petry, C., Ring, S.M., Dunger, D.B., Todd, J.A., Ong, K.K., 2008. Association analysis of the IGF1 gene with childhood growth, IGF-1 concentrations and type 1 diabetes. Diabetologia 51, 811–815.PubMedCrossRefGoogle Scholar
  123. Wang, L., Wang, X., Laird, N., Zuckerman, B., Stubblefield, P., Xu, X., 2006. Polymorphism in maternal LRP8 gene is associated with fetal growth. Am J Hum Genet 78, 770–777.PubMedCrossRefGoogle Scholar
  124. Weedon, M.N., Clark, V.J., Qian, Y., Ben-Shlomo, Y., Timpson, N., Ebrahim, S., Lawlor, D.A., Pembrey, M.E., Ring, S., Wilkin, T.J., Voss, L.D., Jeffery, A.N., Metcalf, B., Ferrucci, L., Corsi, A.M., Murray, A., Melzer, D., Knight, B., Shields, B., Smith, G.D., Hattersley, A.T., Di Rienzo, A., Frayling, T.M., 2006. A common haplotype of the glucokinase gene alters fasting glucose and birth weight: association in six studies and population-genetics analyses. Am J Hum Genet 79, 991–1001.PubMedCrossRefGoogle Scholar
  125. Westergaard, T., Andersen, P.K., Pedersen, J.B., Olsen, J.H., Frisch, M., Sorensen, H.T., Wohlfahrt, J., Melbye, M., 1997. Birth characteristics, sibling patterns, and acute leukemia risk in childhood: a population-based cohort study. J Natl Cancer Inst 89, 939–947.PubMedCrossRefGoogle Scholar
  126. Wilcox, A.J., 2001. On the importance–and the unimportance–of birthweight. Int J Epidemiol 30, 1233–1241.PubMedCrossRefGoogle Scholar
  127. Wilcox, M., Gardosi, J., Mongelli, M., Ray, C., Johnson, I., 1993. Birth weight from pregnancies dated by ultrasonography in a multicultural British population. BMJ 307, 588–591.PubMedCrossRefGoogle Scholar
  128. Wilpshaar, J., Joekes, E.C., Lim, F.T., Van Leeuwen, G.A., Van den Boogaard, P.J., Kanhai, H.H., Willemze, R., Falkenburg, J.H., 2002. Magnetic resonance imaging of fetal bone marrow for quantitative definition of the human fetal stem cell compartment. Blood 100, 451–457.PubMedCrossRefGoogle Scholar
  129. Wong, C.T., Saha, N., 1990. Inter-relationships of storage iron in the mother, the placenta and the newborn. Acta Obstet Gynecol Scand 69, 613–616.PubMedCrossRefGoogle Scholar
  130. Wu, T., Sempos, C.T., Freudenheim, J.L., Muti, P., Smit, E., 2004. Serum iron, copper and zinc concentrations and risk of cancer mortality in US adults. Ann Epidemiol 14, 195–201.PubMedCrossRefGoogle Scholar
  131. Xue, F., Michels, K.B., 2007. Intrauterine factors and risk of breast cancer: a systematic review and meta-analysis of current evidence. Lancet Oncol 8, 1088–1100.PubMedCrossRefGoogle Scholar
  132. Yang, S.W., Yu, J.S., 2000. Relationship of insulin-like growth factor-I, insulin-like growth factor binding protein-3, insulin, growth hormone in cord blood and maternal factors with birth height and birthweight. Pediatr Int 42, 31–36.PubMedCrossRefGoogle Scholar
  133. Yeazel, M.W., Ross, J.A., Buckley, J.D., Woods, W.G., Ruccione, K., Robison, L.L., 1997. High birth weight and risk of specific childhood cancers: a report from the Children’s Cancer Group. J Pediatr 131, 671–677.PubMedCrossRefGoogle Scholar
  134. Yu, H., Rohan, T., 2000. Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst 92, 1472–1489.PubMedCrossRefGoogle Scholar
  135. Yu, H., Shu, X.O., Li, B.D., Dai, Q., Gao, Y.T., Jin, F., Zheng, W., 2003. Joint effect of insulin-like growth factors and sex steroids on breast cancer risk. Cancer Epidemiol Biomarkers Prev 12, 1067–1073.PubMedGoogle Scholar

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© Springer Science+ Business Media, LLC 2010

Authors and Affiliations

  1. 1.Section of Hematology-Oncology, Department of PediatricsChildhood Cancer Epidemiology and Prevention Center, Texas Children’s Cancer Centre, Baylor College of MedicineHoustonUSA

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