The DNMT3B C--T promoter polymorphism and risk of breast cancer in a British population: a case-control study
| Autor: | Karen G. Montgomery, Diana Eccles, Ian G. Campbell, Mira C P Liu |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Methyltransferase Breast Neoplasms Biology medicine.disease_cause polymorphism Cytosine Epigenetics of physical exercise breast cancer medicine Humans Epigenetics DNA (Cytosine-5-)-Methyltransferases Age of Onset Promoter Regions Genetic Aged Genetics Medicine(all) Polymorphism Genetic Promoter Methylation DNA Neoplasm DNA Methylation Middle Aged United Kingdom Case-Control Studies embryonic structures DNA methylation DNMT1 Cancer research Female DNMT3B methylation Carcinogenesis Thymidine Research Article |
| Zdroj: | Breast Cancer Research |
| ISSN: | 1465-542X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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