The DNMT3B C?T promoter polymorphism and risk of breast cancer in a British population: a case-control study
The DNMT3B C?T promoter polymorphism and risk of breast cancer in a British population: a case-control study
Background: gene promoter methylation is an important regulator of expression and is a key epigenetic factor in tumorigenesis. DNA methylation is mediated by DNA methyltransferases (DNMTs), of which three active forms have been identified: DNMT1, DNM3A and DNMT3B. The C?T transition polymorphism (C46359T) in the promoter of the DNMT3B gene, which significantly increases transcriptional activity, has been postulated to increase the propensity for promoter-hypermethylation-mediated silencing of tumour suppressor genes.
Methods: to determine the role of this polymorphism in breast cancer, we genotyped 352 cases and 258 controls from a British population. The breast cancer cases were selected on the basis of either an age at onset of less than 40 years, a family history of breast cancer irrespective of age at onset, or bilateral breast cancer diagnosed after 39 years of age irrespective of family history.
Results: the C allele was found to be more common in case subjects than in control subjects (cases, 0.59; controls, 0.54) corresponding to a nominally significant increase in breast cancer risk to heterozygotes and CC homozygotes (odds ratio 1.51, 95% confidence interval 1.01–2.25) in the dominant inheritance model.
Conclusions: our findings contrast with those of a previous study, which showed that individuals carrying at least one T allele have a significantly increased risk of developing lung cancer. This discrepancy might be an artefact resulting from a chance variation, or it might point to differing influences of promoter hypermethylation in these cancer types.
R390-R394
Montgomery, Karen G.
13ec8448-1ba2-4d0b-8d56-4270be80de0b
Liu, Mira C.P.
c68d64b5-86fa-4c38-9e8e-71edb3a52be7
Eccles, Diana M.
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Campbell, Ian G.
681789cb-d416-4722-9ba8-449c7af96673
2004
Montgomery, Karen G.
13ec8448-1ba2-4d0b-8d56-4270be80de0b
Liu, Mira C.P.
c68d64b5-86fa-4c38-9e8e-71edb3a52be7
Eccles, Diana M.
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Campbell, Ian G.
681789cb-d416-4722-9ba8-449c7af96673
Montgomery, Karen G., Liu, Mira C.P., Eccles, Diana M. and Campbell, Ian G.
(2004)
The DNMT3B C?T promoter polymorphism and risk of breast cancer in a British population: a case-control study.
Breast Cancer Research, 6 (4), .
(doi:10.1186/bcr807).
Abstract
Background: gene promoter methylation is an important regulator of expression and is a key epigenetic factor in tumorigenesis. DNA methylation is mediated by DNA methyltransferases (DNMTs), of which three active forms have been identified: DNMT1, DNM3A and DNMT3B. The C?T transition polymorphism (C46359T) in the promoter of the DNMT3B gene, which significantly increases transcriptional activity, has been postulated to increase the propensity for promoter-hypermethylation-mediated silencing of tumour suppressor genes.
Methods: to determine the role of this polymorphism in breast cancer, we genotyped 352 cases and 258 controls from a British population. The breast cancer cases were selected on the basis of either an age at onset of less than 40 years, a family history of breast cancer irrespective of age at onset, or bilateral breast cancer diagnosed after 39 years of age irrespective of family history.
Results: the C allele was found to be more common in case subjects than in control subjects (cases, 0.59; controls, 0.54) corresponding to a nominally significant increase in breast cancer risk to heterozygotes and CC homozygotes (odds ratio 1.51, 95% confidence interval 1.01–2.25) in the dominant inheritance model.
Conclusions: our findings contrast with those of a previous study, which showed that individuals carrying at least one T allele have a significantly increased risk of developing lung cancer. This discrepancy might be an artefact resulting from a chance variation, or it might point to differing influences of promoter hypermethylation in these cancer types.
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Published date: 2004
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Local EPrints ID: 26489
URI: http://eprints.soton.ac.uk/id/eprint/26489
PURE UUID: b75960cd-9658-4d6e-947a-051969f62120
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Date deposited: 12 Apr 2006
Last modified: 16 Mar 2024 02:39
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Author:
Karen G. Montgomery
Author:
Mira C.P. Liu
Author:
Ian G. Campbell
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