This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gaudet, M. M. Articles by Garcia-Closas, M. Search for Related Content PubMed PubMed Citation Articles by Gaudet, M. M. Articles by Garcia-Closas, M.

Comprehensive Assessment of Genetic Variation of Catechol-O-Methyltransferase and Breast Cancer Risk

¹ Division of Cancer Epidemiology and Genetics and ² Core Genotype Facility at the Advanced Technology Center, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland; ³ Department of Cancer Epidemiology and Prevention, Cancer Center and M. Sklodowska-Curie Institute of Oncology, Warsaw, Poland; and ⁴ Department of Occupational and Environmental Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland

Requests for reprints: Mia M. Gaudet, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, EPS/7055, Rockville, MD 20852. Phone: 301-435-4725; Fax: 301-402-0916; E-mail: gaudetm{at}mail.nih.gov.

Because catechol-O-methyltransferase (COMT) catalyzes the addition of methyl groups to stabilize catechol estrogens that may induce DNA damage, genetic variants could influence breast cancer risk. To comprehensively characterize genetic variation in this gene, we selected haplotype-tagging single nucleotide polymorphisms (htSNP) in COMT. A total of 11 htSNPs (including COMT Val¹⁵⁸Met) were selected based on the resequencing and dense genotyping approach of the Breast and Prostate Cancer Cohort Consortium. htSNPs were genotyped in a population-based, case-control study in Poland (1,995 cases and 2,296 controls). Individual SNPs were not significantly associated with risk. Haplotypes were estimated using the expectation-maximization algorithm. Overall differences in the haplotype distribution between cases and controls were assessed using a global score test. The TGAG haplotype (frequent in 4.3% of controls), in a linkage disequilibrium (LD) block that included the 3' untranslated region (UTR) of COMT, was associated with breast cancer risk (odds ratio, 1.29; 95% confidence interval, 1.06-1.58) compared with the most common haplotype TGAA; however, the global test for haplotype associations was not significant (P = 0.09). Haplotypes in another LD block, which included COMT Val¹⁵⁸Met, were not associated with breast cancer risk (global P = 0.76). Haplotype-breast cancer risk associations were not significantly modified by hormonally related risk factors, family history of breast cancer, or tumor characteristics. In summary, our data does not support a substantial overall association between COMT haplotypes and breast cancer. The suggestion of increased risk associated with a haplotype in the 3' UTR of COMT needs to be confirmed in independent study populations. (Cancer Res 2006; 66(19): 9781-5)

This article has been cited by other articles:

				L. Lehmann, L. Jiang, and J. Wagner Soy isoflavones decrease the catechol-O-methyltransferase-mediated inactivation of 4-hydroxyestradiol in cultured MCF-7 cells Carcinogenesis, February 1, 2008; 29(2): 363 - 370. [Abstract] [Full Text] [PDF]