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

Genetic polymorphisms in microsomal epoxide hydrolase and susceptibility to adult acute myeloid leukaemia with defined cytogenetic abnormalities
Genetic polymorphisms in microsomal epoxide hydrolase and susceptibility to adult acute myeloid leukaemia with defined cytogenetic abnormalities
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).
0007-1048
587-594
Lebailly, P.
1fb59f03-7e4d-4e3e-95b7-6d471bb8f21a
Willett, E.V.
19fa0295-137e-4ce8-b780-5432df7b45bb
Moorman, A.V.
af5027f3-4927-4e62-b1be-ac4bdcf6cd8f
Roman, E.
5f184e94-d01d-40b5-8cbe-6dd6335a850b
Cartwright, R.
0f1f2277-3d1b-4988-9cc4-143f6e495529
Morgan, G.J.
7e5206cc-8a58-410c-9ea5-9022b1532ace
Wild, C.P.
bc319bce-96fc-467f-8a5f-500565fb66ef
Lebailly, P.
1fb59f03-7e4d-4e3e-95b7-6d471bb8f21a
Willett, E.V.
19fa0295-137e-4ce8-b780-5432df7b45bb
Moorman, A.V.
af5027f3-4927-4e62-b1be-ac4bdcf6cd8f
Roman, E.
5f184e94-d01d-40b5-8cbe-6dd6335a850b
Cartwright, R.
0f1f2277-3d1b-4988-9cc4-143f6e495529
Morgan, G.J.
7e5206cc-8a58-410c-9ea5-9022b1532ace
Wild, C.P.
bc319bce-96fc-467f-8a5f-500565fb66ef

Lebailly, P., Willett, E.V., Moorman, A.V., Roman, E., Cartwright, R., Morgan, G.J. and Wild, C.P. (2002) Genetic polymorphisms in microsomal epoxide hydrolase and susceptibility to adult acute myeloid leukaemia with defined cytogenetic abnormalities. British Journal of Haematology, 116 (3), 587-594. (doi:10.1046/j.0007-1048.2001.03320.x).

Record type: Article

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).

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Published date: 2002

Identifiers

Local EPrints ID: 26433
URI: http://eprints.soton.ac.uk/id/eprint/26433
ISSN: 0007-1048
PURE UUID: c283071b-eb31-4e22-a0f8-c07dcded1f3e

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Date deposited: 24 Apr 2006
Last modified: 15 Jul 2019 19:14

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