Journal Article

Catechol-<i>O</i>-methyltransferase gene polymorphism and post-menopausal breast cancer risk

Sara Wedrén, Tove Rylander Rudqvist, Fredrik Granath, Elisabete Weiderpass, Magnus Ingelman-Sundberg, Ingemar Persson and Cecilia Magnusson

in Carcinogenesis

Volume 24, issue 4, pages 681-687
Published in print April 2003 | ISSN: 0143-3334
Published online April 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgg022
Catechol-O-methyltransferase gene polymorphism and post-menopausal breast cancer risk

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Estrogen is involved in breast carcinogenesis. Hypotheses have been raised that its effect is modified by enzymes such as catechol-O-methyltransferase (COMT) that deactivate potentially genotoxic estrogen metabolites. We have investigated the association between the functional genetic Val108/158Met polymorphism in COMT and breast cancer risk in a large population-based case–control study performed in the genetically homogeneous Swedish population. We determined COMT genotype in 1534 women with invasive breast cancer and in 1504 control women and calculated odds ratios (OR) and 95% confidence intervals (CI) from logistic regression models. There was no overall association between COMT genotype and breast cancer risk. However, the L allele was associated with an increased risk for lobular breast cancer, with OR 2.0 (95% CI 1.2–3.5) for HL and 1.7 (95% CI 0.9–3.0) for LL. In exploratory subset analyses, we found no statistically significant interaction, but some indication of a positive association between HL and LL genotypes and breast cancer among women with diabetes mellitus and a negative association among nulliparous women. Based on our findings, COMT activity alone does not seem to play a major role in breast carcinogenesis, but may be of importance in certain histotypes or in conjunction with other exposures.

Keywords: BMI, body mass index; CI, confidence interval; COMT, catechol-O-methyltransferase; DASH, dynamic allele-specific hybridization; NIDDM, non-insulin-dependent diabetes; OR, odds ratios; SNP, single nucleotide polymorphism.

Journal Article.  4781 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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