Maternal and Offspring Genetic Variants of AKR1C3 and the Risk of Childhood Leukemia

Details

• Personal Author:
  Christiani, David C. ; Ho C-K ; Hsu Y-H ; Li Y ; Liu C-Y ; Pan P-C ; Su L ; Wu M-T ; Xu X
• Corporate Authors:
  Kaohsiung Leukemia Research Group
• Description:
  The aldo-keto reductase 1C3 (AKR1C3) gene located on chromosome 10p15-p14, a regulator of myeloid cell proliferation and differentiation, represents an important candidate gene for studying human carcinogenesis. In a prospectively enrolled population-based case-control study of Han Chinese conducted in Kaohsiung in southern Taiwan, a total of 114 leukemia cases and 221 controls <20 years old were recruited between November 1997 and December 2005. The present study set out to evaluate the association between childhood leukemia and both maternal and offspring's genotypes. To do so, we conducted a systematic assessment of common single-nucleotide polymorphisms (SNPs) at the 5' flanking 10 kb to 3' UTR of AKR1C3 gene. Gln5His and three tagSNPs (rs2245191, rs10508293 and rs3209896) and one multimarker (rs2245191, rs10508293 and rs3209896) were selected with average 90% coverage of untagged SNPs by using the HapMap II data set. Odds ratios and 95% confidence intervals were adjusted for age and gender. After correcting for multiple comparisons, we observed that risk of developing childhood leukemia is significantly associated with rs10508293 polymorphism on intron 4 of the AKR1C3 gene in both offspring alone and in the combined maternal and offspring genotypes (nominal P < 0.0001, permutation P < 0.005). The maternal methylenetetrahydrofolate reductase A1298C polymorphism was found to be an effect modifier of the maternal intron 4 polymorphism of the AKR1C3 gene (rs10508293) and the childhood leukemia risk. In conclusion, this study suggests that AKR1C3 polymorphisms may be important predictive markers for childhood leukemia susceptibility. [Description provided by NIOSH]
• Subjects:
  Aging Carcinogens Demography Epidemiology Genetics Men Neoplasms Occupational Health Race Factors Risk Assessment Risk Factors Safety Women

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• Keywords:
  Age Groups Cancer Carcinogenesis Case Control Studies Children Demographic Characteristics Genes Genotype Humans Racial Factors Risk Factors Statistical Analysis

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• ISSN:
  0143-3334
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Massachusetts ; OSHA Region 1
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  29
• Issue:
  5
• NIOSHTIC Number:
  nn:20057503
• Citation:
  Carcinogenesis 2008 May; 29(5):984-990
• Contact Point Address:
  David C.Christiani, 1Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115
• Email:
  dchris@hsph.harvard.edu
• Federal Fiscal Year:
  2008
• Performing Organization:
  Harvard School of Public Health
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Carcinogenesis
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1ba778ec431316cbdab7ec58fe2f80736ca3dbd9f649ad233b2304168aa085c51c1a89886d2cc9644b9c4a961c9bd6029fb506a1769937738e9422614bb22207
• Download URL:
  https://stacks.cdc.gov/view/cdc/214841/cdc_214841_DS1.pdf
• File Type:
  [PDF - 101.03 KB ]