Abstract
Background
Higher birth weight and maternal history of miscarriage has been associated with an increased risk of childhood leukemia. The possibility that this association may be sex-specific has not been explored in detail in previous studies.
Methods
In a retrospective case-control study, 732 childhood (≤14 years) cancer cases from a population-based Registry in Northern England whose hospital birth records could be accessed and 3,723 controls matched for date and hospital of birth to the cases were compared. We examined birth weight for sex-specific associations with childhood cancer. Conditional logistic regression analysis was used for statistical evaluation of associations.
Results
In acute lymphoblastic leukemia (ALL) (225 cases and 1,163 matched controls), birth weight and sex showed a strong interaction (P = 0.003). In boys with ALL, but not in girls, there was a nonlinear association with birth weight (P for trend = 0.008; OR = 3.05 for the highest quintile compared to the second lowest quintile, 95% CI = 1.40–6.64; P = 0.005). When birth weights were adjusted using UK standards for gestational age and sex, the risk associations were similar in statistical significance and magnitude. Maternal history of miscarriage showed an association with all cancers and individually with ALL. The miscarriage association with ALL was statistically significant in boys only (OR = 1.91, 95% CI = 1.07–3.42; P = 0.03). A multivariable model for ALL containing other examined maternal and reproductive variables confirmed the independence of the birth weight and miscarriage associations. There was no birth weight or miscarriage associations in other cancers.
Conclusions
This study confirmed the risk associations with birth weight and miscarriages in childhood ALL. Statistically significant association of size at birth suggested marked differences in etiology between girls and boys.
Similar content being viewed by others
References
Linet MS, Wacholder S, Zahm SH (2003) Interpreting epidemiologic research: lessons from studies of childhood cancer. Pediatrics 112(1 Pt 2):218–232
Daling JR, Starzyk P, Olshan AF, Weiss NS (1984) Birth weight and the incidence of childhood cancer. J Natl Cancer Inst 72(5):1039–1041
Westergaard T, Andersen PK, Pedersen JB, et al. (1997) Birth characteristics, sibling patterns, and acute leukemia risk in childhood: a population-based cohort study. J Natl Cancer Inst 89(13):939–947
Yeazel MW, Ross JA, Buckley JD, Woods WG, Ruccione K, Robison LL (1997) High birth weight and risk of specific childhood cancers: a report from the Children’s Cancer Group. J Pediatr 131(5):671–677
Schuz J, Kaletsch U, Meinert R, Kaatsch P, Spix C, Michaelis J (2001) Risk factors for neuroblastoma at different stages of disease. Results from a population-based case–control study in Germany. J Clin Epidemiol 54(7):702–709
Schuz J, Kaletsch U, Meinert R, Kaatsch P, Michaelis J (2001) High-birth weight and other risk factors for Wilms tumour: results of a population-based case–control study. Eur J Pediatr 160(6):333–338
Murray L, McCarron P, Bailie K, et al. (2002) Association of early life factors and acute lymphoblastic leukaemia in childhood: historical cohort study. Br J Cancer 86(3):356–361
Okcu MF, Goodman KJ, Carozza SE, et al. (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(7):595–602
Hjalgrim LL, Westergaard T, Rostgaard K, et al. (2003) Birth weight as a risk factor for childhood leukemia: a meta-analysis of 18 epidemiologic studies. Am J Epidemiol 158(8):724–735
Hjalgrim LL, Rostgaard K, Hjalgrim H, et al. (2004) Birth weight and risk for childhood leukemia in Denmark, Sweden, Norway, and Iceland. J Natl Cancer Inst 96(20):1549–1556
Roman E, Simpson J, Ansell P, Lightfoot T, Mitchell C, Eden TO (2005) Perinatal and reproductive factors: a report on haematological malignancies from the UKCCS. Eur J Cancer 41(5):749–759
McLaughlin CC, Baptiste MS, Schymura MJ, Nasca PC, Zdeb MS (2006) Birth weight, maternal weight and childhood leukaemia. Br J Cancer 94(11):1738–1744
Reynolds P, Von Behren J, Elkin EP (2002) Birth characteristics and leukemia in young children. Am J Epidemiol 155(7):603–613
Ross JA, Perentesis JP, Robison LL, Davies SM (1996) Big babies and infant leukemia: a role for insulin-like growth factor-1? Cancer Causes Control 7(5):553–559
Vorwerk P, Wex H, Hohmann B, Mohnike K, Schmidt U, Mittler U (2002) Expression of components of the IGF signalling system in childhood acute lymphoblastic leukaemia. Mol Pathol 55(1):40–45
Albanes D, Winick M (1988) Are cell number and cell proliferation risk factors for cancer? J Natl Cancer Inst 80(10):772–774
Albanes D (1990) Energy balance, body size, and cancer. Crit Rev Oncol Hematol 10(3):283–303
Hindmarsh PC, Geary MP, Rodeck CH, Kingdom JC, Cole TJ (2002) Intrauterine growth and its relationship to size and shape at birth. Pediatr Res 52(2):263–268
Storms MR, Van Howe RS (2004) Birthweight by gestational age and sex at a rural referral center. J Perinatol 24(4):236–240
Schuz J, Kaatsch P, Kaletsch U, Meinert R, Michaelis J (1999) Association of childhood cancer with factors related to pregnancy and birth. Int J Epidemiol 28(4):631–639
McNally RJ, Rowland D, Roman E, Cartwright RA (1997) Age and sex distributions of hematological malignancies in the U.K. Hematol Oncol 15(4):173–189
Pearce MS, Parker L (2001) Childhood cancer registrations in the developing world: still more boys than girls. Int J Cancer 91(3):402–406
Cartwright RA, Gurney KA, Moorman AV (2002) Sex ratios and the risks of haematological malignancies. Br J Haematol 118(4):1071–1077
Taylor GM, Dearden S, Payne N, et al. (1998) Evidence that an HLA-DQA1-DQB1 haplotype influences susceptibility to childhood common acute lymphoblastic leukaemia in boys provides further support for an infection-related aetiology. Br J Cancer 78(5):561–565
Dorak MT, Lawson T, Machulla HK, Darke C, Mills KI, Burnett AK (1999) Unravelling an HLA-DR association in childhood acute lymphoblastic leukemia. Blood 94(2):694–700
Dorak MT, Sproul AM, Gibson BE, Burnett AK, Worwood M (1999) The C282Y mutation of HFE is another male-specific risk factor for childhood ALL. Blood 94(11):3957–3958
Dorak MT, Oguz FS, Yalman N, et al. (2002) A male-specific increase in the HLA-DRB4 (DR53) frequency in high-risk and relapsed childhood ALL. Leuk Res 26(7):651–656
Dorak MT, Lawson T, Machulla HK, Mills KI, Burnett AK (2002) Increased heterozygosity for MHC class II lineages in newborn males. Genes Immun 3(5):263–269
Hewitt D, Lashof JC, Stewart AM (1966) Childhood cancer in twins. Cancer 19(2):157–161
Inskip PD, Harvey EB, Boice JD Jr, et al. (1991) Incidence of childhood cancer in twins. Cancer Causes Control 2(5):315–324
Pinn VW (2003) Sex and gender factors in medical studies: implications for health and clinical practice. JAMA 289(4):397–400
Cotterill SJ, Parker L, Malcolm AJ, Reid M, More L, Craft AW (2000) Incidence and survival for cancer in children and young adults in the North of England, 1968–1995: a report from the Northern Region Young Persons’ Malignant Disease Registry. Br J Cancer 83(3):397–403
Parker L, Cole M, Craft AW, Hey EN (1998) Neonatal vitamin K administration and childhood cancer in the north of England: retrospective case–control study. BMJ316 7126:189–193
Wilcox M, Gardosi J, Mongelli M, Ray C, Johnson I (1993) Birth weight from pregnancies dated by ultrasonography in a multicultural British population. BMJ307 6904:588–591
Royston P, Ambler G, Sauerbrei W (1999) The use of fractional polynomials to model continuous risk variables in epidemiology. Int J Epidemiol 28(5):964–974
Kaye SA, Robison LL, Smithson WA, Gunderson P, King FL, Neglia JP (1991) Maternal reproductive history and birth characteristics in childhood acute lymphoblastic leukemia. Cancer 68(6):1351–1355
Stewart A, Webb J, Hewitt D (1958) A survey of childhood malignancies. BMJ 1:1495–1508
Gibson RW, Bross IDJ, Graham S, et al. (1968) Leukemia in children exposed to multiple risk factors. New Engl J Med 279(17):906–909
Yeazel MW, Buckley JD, Woods WG, Ruccione K, Robison LL (1995) History of maternal fetal loss and increased risk of childhood acute leukemia at an early age. A report from the Childrens Cancer Group. Cancer 75(7):1718–1727
McMillen MM (1979) Differential mortality by sex in fetal and neonatal deaths. Science 204(4388):89–91
Dorak MT, Burnett AK (1992) Major histocompatibility complex, t-complex, and leukemia. Cancer Causes Control 3(3):273–282
Melve KK, Skjaerven R (2003) Birthweight and perinatal mortality: paradoxes, social class, and sibling dependencies. Int J Epidemiol 32(4):625–632
Petridou E, Skalkidou A, Dessypris N, et al. (2000) Endogenous risk factors for childhood leukemia in relation to the IGF system (Greece). The Childhood Haematologists–Oncologists Group. Cancer Causes Control 11(8):765–771
Preston-Martin S, Pike MC, Ross RK, Jones PA, Henderson BE (1990) Increased cell division as a cause of human cancer. Cancer Res 50(23):7415–7421
Srivastava S, Mehrotra PK, Srivastava SP, Siddiqui MK (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(2):97–105
Cogswell ME, Parvanta I, Ickes L, Yip R, Brittenham GM (2003) Iron supplementation during pregnancy, anemia, and birth weight: a randomized controlled trial. Am J Clin Nutr 78(4):773–781
Le NT, Richardson DR (2002) The role of iron in cell cycle progression and the proliferation of neoplastic cells. Biochim Biophys Acta 1603(1):31–46
Dorak MT, Burnett AK, Worwood M (2005) HFE gene mutations in susceptibility to childhood leukemia: HuGE review. Genet Med 7(3):159–168
Lao TT, Chan PL, Tam KF (2001) Gestational diabetes mellitus in the last trimester—a feature of maternal iron excess? Diabet Med 18(3):218–223
Cauza E, Hanusch-Enserer U, Bischof M, et al. (2005) Increased C282Y heterozygosity in gestational diabetes. Fetal Diagn Ther 20(5):349–354
Feltbower RG, McKinney PA, Greaves MF, Parslow RC, Bodansky HJ (2004) International parallels in leukaemia and diabetes epidemiology. Arch Dis Child 89(1):54–56
Acknowledgments
The original study was funded by the Department of Health (UK). MTD is supported by the North of England Children’s Cancer Research Fund. The Northern Region Young Persons’ Malignant Disease Registry is funded by the Newcastle Hospitals NHS Trust.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Dorak, M.T., Pearce, M.S., Hammal, D.M. et al. Examination of gender effect in birth weight and miscarriage associations with childhood cancer (United Kingdom). Cancer Causes Control 18, 219–228 (2007). https://doi.org/10.1007/s10552-006-0093-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10552-006-0093-8