Genetic polymorphisms in microsomal epoxide hydrolase and susceptibility to adult acute myeloid leukaemia with defined cytogenetic abnormalities

Christopher P. Wild, Ray Cartwright, Eve Roman, Anthony V. Moorman, Eleanor V. Willett, Gareth J. Morgan

Research output: Contribution to journalArticle

Abstract

Acute myeloid leukaemia (AML) cases with different chromosomal abnormalities may reflect different aetiologies. Benzene exposure, from a number of sources including smoking, is one risk factor for AML. Individual susceptibility to benzene may depend on differences in expression of metabolizing enzymes. We tested the hypothesis that smoking as well as genetic polymorphisms in the microsomal epoxide hydrolase gene (HYL1), an enzyme involved in benzene metabolism, could be risk factors for AML with defined chromosomal abnormalities. Twenty-six AML cases with -7/del(7q) and 24 cases with t(8;21), as well as 43 cases with normal karyotype and 155 age-, sex- and residence-matched controls, were drawn from a large case-control study on adult acute leukaemia. Current smoking was significantly associated with the cytogenetic abnormalities t(8;21) or -7/del(7q) (OR = 4.9; 95%CI = 2.1-11.5) but not with a normal karyotype, relative to individuals who were not current smokers. A putative high activity HYL1 phenotype [exon 3, residue 113 (Tyr/Tyr) and exon 4, residue 139 (His/Arg or Arg/Arg)] was associated with a significantly increased AML risk in men with -7/del(7q) or t(8;21) (OR = 4.4; 95%CI 1.1-17.0) but not with a normal karyotype. This suggests that AML cases with defined chromosomal abnormalities could be related to specific carcinogen exposures and, furthermore, suggests that smoking and genetic polymorphisms in HYL1 could be risk factors for AML with -7/del(7q) or t(8;21).

Original languageEnglish (US)
Pages (from-to)587-594
Number of pages8
JournalBritish journal of haematology
Volume116
Issue number3
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

Keywords

  • Acute myeloid leukaemia
  • Cytogenetic abnormalities
  • Genetic susceptibility
  • Microsomal epoxide hydrolase
  • Tobacco smoke

ASJC Scopus subject areas

  • Hematology

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