Original Article

Inverse Correlation of Lymphoid Leukemia Incidence and Anemia Prevalence among Preschool Children

Authors: Frank D. Groves, MD, MPH

Abstract

Objective: The relation between the prevalence of anemia and incidence of childhood acute lymphoblastic leukemia was explored using international cross-sectional data as well as US time-series data.

Methods: Lymphoid leukemia incidence rates for various countries from the International Agency for Research on Cancer were regressed on anemia prevalence rates from the World Health Organization in a cross-sectional analysis. Four decades of acute lymphoblastic leukemia incidence (from the Surveillance, Epidemiology, and End Results Program cancer registries) and anemia prevalence (from the National Health and Nutrition Examination Survey) also were examined in a time-series analysis.

Results: There was a statistically significant inverse correlation between leukemia incidence and anemia prevalence in 53 countries, with leukemia incidence being highest in those countries where anemia prevalence was lowest. Examination of US leukemia incidence and anemia prevalence trends from 1973 through 2012 revealed similarly contrasting trends, with leukemia incidence increasing while anemia prevalence was decreasing. White children had half as much anemia but twice as much leukemia as black children.

Conclusions: It is postulated that the iron-depleted state may be unfavorable to leukemogenesis, perhaps because lymphopoiesis is suppressed when erythropoiesis is stimulated. Conversely, the iron-replete state may be more favorable to leukemogenesis.

 

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

1. World Health Organization, International Agency for Research on Cancer. Cancer incidence in five continents, Vol X. http://ci5.iarc.fr. Published 2013. Accessed July 26, 2016.
 
2. World Health Organization, Centers for Disease Control and Prevention. Worldwide prevalence of anaemia 1993-2005.WHO Global Database on Anaemia. http://apps.who.int/iris/bitstream/10665/43894/1/9789241596657_eng.pdf. Accessed July 26, 2016.
 
3. Hewitt D. Some features of leukaemia mortality. Br J Prev Soc Med 1955;9:81-88.
 
4. Gilliam AG, Walter WA. Trends in mortality from leukemia in the United States, 1921-1955. Public Health Rep 1958;73:773-784.
 
5. Court Brown WM, Doll R. Leukaemia in childhood and young adult life: trends in mortality in relation to aetiology. BMJ 1961;1:981-988.
 
6. Fraumeni JF, Jr Miller RW. Epidemiology of human leukemia: recent observations. J Natl Cancer Inst 1967;38:593-605.
 
7. van Hoff J, Schymura MJ, Curnen MG. Trends in the incidence of childhood and adolescent cancer in Connecticut, 1935-1979. Med Pediatr Oncol 1988;16:78-87.
 
8. American Academy of Pediatrics Committee Statement. The Ten-State Nutrition Survey: a pediatric perspective. Pediatrics 1973;51:1095-1099.
 
9. Owen GM, Kram KM, Garry PJ, et al. A study of nutritional status of preschool children in the United States, 1968-1970. Pediatrics 1974;53( suppl ):597-646.
 
10. Miller V, Swaney S, Deinard A. Impact of the WIC program on the iron status of infants. Pediatrics 1985;75:100-105.
 
11. Diet and iron status, a study of relationships: United States, 1971-74. Data from the National Health Survey. Series 11, No. 229. Vital Health Stat 11 1982;229:1-83.
 
12. Dallman PR, Yip R, Johnson C. Prevalence and causes of anemia in the United States, 1976 to 1980. Am J Clin Nutr 1984;39:437-445.
 
13. Cusick SE, Mei Z, Freedman DS, et al. Unexplained decline in the prevalence of anemia among US children and women between 1988-1994 and 1999-2002. Am J Clin Nutr 2008;88:1611-1617.
 
14. Singbrant S, Russell MR, Jovic T, et al. Erythropoietin couples erythropoiesis, B-lymphopoiesis, and bone homeostasis within the bone marrow microenvironment. Blood 2011;117:5631-5642.
 
15. Dorak MT, Mackay RK, Relton CL, et al. Hereditary hemochromatosis gene (HFE) variants are associated with birth weight and childhood leukemia risk. Pediatr Blood Cancer 2009;53:1242-1248.
 
16. Kwan ML, Buffler PA, Abrams B, et al. Breastfeeding and the risk of childhood leukemia: a meta-analysis. Public Health Rep 2004;119:521-535.
 
17. Martin RM, Gunnell D, Owen CG, et al. Breast-feeding and childhood cancer: a systematic review with meta-analysis. Int J Cancer 2005;117: 1020-1031.
 
18. Kling PJ, Sullivan TM, Roberts RA, et al. Human milk as a potential enteral source of erythropoietin. Pediatr Res 1998;43:216-221.
 
19. Juul SE, Zhao Y, Dame JB, et al. Origin and fate of erythropoietin in human milk. Pediatr Res 2000;48:660-667.
 
20. Greenop KR, Bailey HD, Miller M, et al. Breastfeeding and nutrition to 2 years of age and risk of childhood acute lymphoblastic leukemia and brain tumors. Nutr Cancer 2015;67:431-441.
 
21. Schraw JM, Dong YQ, Okcu MF, et al. Do longer formula feeding and later introduction of solid foods increase risk of pediatric acute lymphoblastic leukemia? Cancer Causes Control 2014;25:73-80.
 
22. Ross JA, Perentesis JP, Robison LL, et al. Big babies and infant leukemia: a role for insulin-like growth factor-1? Cancer Causes Control 1996;7:553-559.
 
23. Callan AC, Milne E. Involvement of the IGF system in fetal growth and childhood cancer: an overview of potential mechanisms. Cancer Causes Control 2009;20:1783-1798.
 
24. Tower RL, Spector LG. The epidemiology of childhood leukemia with a focus on birth weight and diet. Crit Rev Clin Lab Sci 2007;44:203-242.
 
25. Sarasua S, Savitz DA. Cured and broiled meat consumption in relation to childhood cancer: Denver, Colorado (United States). Cancer Causes Control 1994;5:141-148.
 
26. Peters JM, Preston-Martin S, London SJ, et al. Processed meats and risk of childhood leukemia (California USA). Cancer Causes Control 1994;5: 195-202.
 
27. Kwan ML, Block G, Selvin S, et al. Food consumption by children and the risk of childhood acute leukemia. Am J Epidemiol 2004;160:1098-1107.
 
28. Petridou E, Ntouvelis E, Dessypris N, et al. Maternal diet and acute lymphoblastic leukemia in young children. Cancer Epidemiol Biomarkers Prev 2005;14:1935-1939.
 
29. Jensen CD, Block G, Buffler P, et al. Maternal dietary risk factors in childhood acute lymphoblastic leukemia (United States). Cancer Causes Control 2004;15:559-570.
 
30. Thompson JR, Gerald PF, Willoughby ML, et al. Maternal folate supplementation in pregnancy and protection against acute lymphoblastic leukaemia in childhood: a case-control study. Lancet 2001;358:1935-1940.
 
31. Bailey HD, Miller M, Langridge A, et al. Maternal dietary intake of folate and vitamins B6 and B12 during pregnancy and the risk of childhood acute lymphoblastic leukemia. Nutr Cancer 2012;64:1122-1130.
 
32. Wiemels JF, Smith RN, Taylor GM, et al. Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia. Proc Natl Acad Sci U S A 2001;98: 4004-4009.
 
33. Franco RF, Simoes BP, Tone LG, et al. The methylenetetrahydrofolate reductase C677T gene polymorphism decreases the risk of childhood acute lymphocytic leukaemia. Br J Haematol 2001;115:616-618.
 
34. Krajinovic M, Lamothe S, Labuda D, et al. Role of MTHFR genetic polymorphisms in the susceptibility to childhood acute lymphoblastic leukemia. Blood 2004;103:252-257.
 
35. Mezei G, Sudan M, Izraeli S, et al. Epidemiology of childhood leukemia in the presence and absence of Down syndrome. Cancer Epidemiol 2014;38: 479-489.
 
36. Goldacre MJ, Wotton CJ, Seagroatt V, et al. Cancers and immune related diseases associated with Down’ syndrome: a record linkage study. Arch Dis Child 2004;89:1014-1017.
 
37. Bjorge T, Cnattingius S, Lie RT, et al. Cancer risk in children with birth defects and in their families: a population based cohort study of 5.2 million children from Norway and Sweden. Cancer Epidemiol Biomarkers Prev 2008;17:500-506.
 
38. Boker LK, Blumstein T, Sadetzki S, et al. Incidence of leukemia and other cancers in Down syndrome subjects in Israel. Int J Cancer 2001;93: 741-744.
 
39. van Steensel-Moll HA, Valkenburg HA, Vandenbroucke JP, et al. Are maternal fertility problems related to childhood leukaemia? Int J Epidemiol 1985;14:555-559.
 
40. McKinney PA, Juszczak E, Findlay E, et al. Pre- and perinatal risk factors for childhood leukaemia and other malignancies: a Scottish case control study. Br J Cancer 1999;80:1844-1851.
 
41. Rajaraman P, Simpson J, Neta G, et al. Early life exposure to diagnostic radiation and ultrasound scans and risk of childhood cancer: case-control study. BMJ 2011;342:d472.
 
42. Bartley K, Metayer C, Selvin S, et al. Diagnostic X-rays and risk of childhood leukaemia. Int J Epidemiol 2010;39:1628-1637.
 
43. Pearce MS, Salotti JA, Little MP, et al. Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study. Lancet 2012;380:499-505.
 
44. Greenland S, Sheppard AR, Kaune WT, et al. A pooled analysis of magnetic fields, wire codes, and childhood leukemia. Childhood Leukemia-EMF Study Group. Epidemiology 2000;11:624-634.
 
45. Ahlbom A, Day N, Feychting M, et al. A pooled analysis of magnetic fields and childhood leukaemia. Br J Cancer 2000;83:692-698.
 
46. Kheifets L, Ahlbom A, Crespi CM, et al. Pooled analysis of recent studies on magnetic fields and childhood leukaemia. Br J Cancer 2010;103:1128-1135.
 
47. Shu XO, Stewart P, Wen WQ, et al. Parental occupational exposure to hydrocarbons and risk of acute lymphocytic leukemia in offspring. Cancer Epidemiol Biomarkers Prev 1999;8:783-791.
 
48. Schuz J, Kaletsch U, Meinert R, et al. Risk of childhood leukemia and parental self-reported occupational exposure to chemicals, dusts, and fumes: results from pooled analyses of German population-based case-control studies. Cancer Epidemiol Biomarkers Prev 2000;9:835-838.
 
49. Wigle DT, Turner MC, Krewski D. A systematic review and meta-analysis of childhood leukemia and parental occupational pesticide exposure. Environ Health Perspect 2009;117:1505-1513.
 
50. Freedman DM, Stewart P, Kleinerman RA, et al. Household solvent exposures and childhood acute lymphoblastic leukemia. Am J Public Health 2001;91:564-567.
 
51. Scelo G, Metayer C, Zhang L, et al. Household exposure to paint and petroleum solvents, chromosomal translocations, and the risk of childhood leukemia. Environ Health Perspect 2009;117:133-139.
 
52. Bailey HD, Milne E, de Klerk NH, et al. Exposure to house painting and the use of floor treatments and the risk of childhood acute lymphoblastic leukemia. Int J Cancer 2011;128:2405-2414.
 
53. Bailey HD, Metayer C, Milne E, et al. Home paint exposures and risk of childhood acute lymphoblastic leukemia: findings from the Childhood Leukemia International Consortium. Cancer Causes Control 2015;26: 1257-1270.
 
54. Meinert R, Schuz J, Kaletsch U, et al. Leukemia and non-Hodgkin’ lymphoma in childhood and exposure to pesticides: results of a register-based case-control study in Germany. Am J Epidemiol 2000;151:639-650.
 
55. Metayer C, Buffler PA. Residential expsoures to pesticides and childhood leukaemia. Radiat Prot Dosimetry 2008;132:212-219.
 
56. Van Maele-Fabry G, Lantin AC, Hoet P, et al. Residential exposure to pesticides and childhood leukaemia: a systematic review and meta-analysis. Environ Int 2011;37:280-291.
 
57. Bailey HD, Armstrong BK, de Klerk NH, et al. Exposure to professional pest control treatments and the risk of childhood acute lymphoblastic leukemia. Int J Cancer 2011;129:1678-1688.
 
58. Bailey HD, Infante-Rivard C, Metayer C, et al. Home pesticide exposures and risk of childhood leukemia: findings from the Childhood Leukemia International Consortium. Int J Cancer 2015;137:2644-2663.
 
59. Turner MC, Wigle DT, Krewski D. Residential pesticides and childhood leukemia: a systematic review and meta-analysis. Environ Health Perspect 2010;118:33-41.
 
60. Ramot B, Magrath I. Hypothesis: the environment is a major determinant of the immunological sub-type of lymphoma and acute lymphoblastic leukaemia in children. Br J Haematol 1982;50:183-189.
 
61. Greaves MF. Speculations on the cause of childhood acute lymphoblastic leukemia. Leukemia 1988;2:120-125.
 
62. Reeves JD, Yip R, Kiley VA, et al. Iron deficiency in infants: the influence of mild antecedent infection. J Pediatr 1984;105:874-879.
 
63. Olivares M, Walter T, Osorio M, et al. Anemia of a mild viral infection: the measles vaccine as a model. Pediatrics 1989;84:851-855.
 
64. Haneberg B, Matre R, Winsnes R, et al. Acute hemolytic anemia related to diphtheria-pertussis-tetanus vaccination. Acta Paediatr Scand 1978;67: 345-350.