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Combined effect of CCND1 and COMT polymorphisms and increased breast cancer risk.

Authors: Onay, UV  Aaltonen, K  Briollais, L  Knight, JA  Pabalan, N  Kilpivaara, O  Andrulis, IL  Blomqvist, C  Nevanlinna, H  Ozcelik, H 
Citation: Onay UV, etal., BMC Cancer. 2008 Jan 14;8(1):6.
Pubmed: (View Article at PubMed) PMID:18194538
DOI: Full-text: DOI:10.1186/1471-2407-8-6

ABSTRACT: BACKGROUND: Estrogens are crucial tumorigenic hormones, which impact the cell growth and proliferation during breast cancer development. Estrogens are metabolized by a series of enzymes including COMT, which converts catechol estrogens into biologically non-hazardous methoxyestrogens. Several studies have also shown the relationship between estrogen and cell cycle progression through activation of CCND1 transcription. METHODS: In this study, we have investigated the independent and the combined effects of commonly occurring CCND1 (Pro241Pro, A870G) and COMT (Met108/158Val) polymorphisms to breast cancer risk in two independent Caucasian populations from Ontario (1228 breast cancer cases and 719 population controls) and Finland (728 breast cancer cases and 687 population controls). Both COMT and CCND1 polymorphisms have been previously shown to impact on the enzymatic activity of the coded proteins. RESULTS: Here, we have shown that the high enzymatic activity genotype of CCND1 High (AA) was associated with increased breast cancer risk in both the Ontario [OR: 1.3, 95%CI (1.0-1.69)] and the Finland sample [OR: 1.4, 95%CI (1.01-1.84)]. The heterozygous COMT Medium (MetVal) and the high enzymatic activity of COMT High (ValVal) genotype was also associated with breast cancer risk in Ontario cases, [OR: 1.3, 95%CI (1.07-1.68)] and [OR: 1.4, 95%CI (1.07-1.81)], respectively. However, there was neither a statistically significant association nor increased trend of breast cancer risk with COMT High (ValVal) genotypes in the Finland cases [OR: 1.0, 95%CI (0.73-1.39)]. In the combined analysis, the higher activity alleles of the COMT and CCND1 is associated with increased breast cancer risk in both Ontario [OR: 2.22, 95%CI (1.49-3.28)] and Finland [OR: 1.73, 95%CI (1.08-2.78)] populations studied. The trend test was statistically significant in both the Ontario and Finland populations across the genotypes associated with increasing enzymatic activity. CONCLUSION: Using two independent Caucasian populations, we have shown a stronger combined effect of the two commonly occurring CCND1 and COMT genotypes in the context of breast cancer predisposition.

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RGD Object Information
RGD ID: 2289126
Created: 2008-01-23
Species: All species
Last Modified: 2008-01-23
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.