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.
Montgomery
Karen G
KG
Victorian Breast Cancer Research Consortium, Cancer Genetics Laboratory, Peter MacCallum Cancer Center, East Melbourne, Victoria, Australia. karen.montgomery@petermac.org
Liu
Mira C P
MC
Eccles
Diana M
DM
Campbell
Ian G
IG
D000328:Adult; D017668:Age of Onset; D000368:Aged; D001943:Breast Neoplasms / Q000201:enzymology / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D003596:Cytosine / Q000378:metabolism*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013936:Thymidine / Q000378:metabolism*; D006113:United Kingdom / Q000453:epidemiology; D000097584:DNA Methyltransferase 3B
D003596:Cytosine; D004248:DNA (Cytosine-5-)-Methyltransferases; D004273:DNA, Neoplasm; D013936:Thymidine; D000097584:DNA Methyltransferase 3B