The DNMT3B C→T promoter polymorphism and risk of breast cancer in a British population: a case-control study

Breast Cancer Research

Ian G Campbell²  Diana M Eccles¹  Mira CP Liu²  Karen G Montgomery² 

[1] Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK;Victorian Breast Cancer Research Consortium, Cancer Genetics Laboratory, Peter MacCallum Cancer Center, East Melbourne, Victoria, Australia

关键词: polymorphism;    methylation;    DNMT3B;    breast cancer;   

Others  :  1118742
DOI  :  10.1186/bcr807

 received in 2004-02-05, accepted in 2004-04-30,  发布年份 2004

【 摘 要 】

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.

【 授权许可】

   
2004 Montgomery et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

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